MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Cell Division' source. Tue, 07 Feb 2012 08:48:53 +0100 http://www.medworm.com/index.php?rid=5665145&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F7%2F1%2F3 Regulation of cell cycle progression is important for the maintenance of genome integrity, and Polo-like kinases (Plks) have been identified as key regulators of this process. It is well established that Polo-like kinase 1 (Plk1) plays critical roles in mitosis but little is known about its functions at other stages of the cell cycle. Here we summarize the functions of Plk1 during DNA replication, focusing on the molecular events related to Origin Recognition Complex (ORC), the complex that is essential for the initiation of DNA replication. Within the context of Plk1 phosphorylation of Orc2, we also emphasize regulation of Orc2 in different organisms. This review is intended to provide some insight into how Plk1 coordinates DNA replication in S phase with chromosome segregation in mitosis... Cell Division journals http://www.medworm.com/rss/comments.php?id=5665145 Mon, 06 Feb 2012 05:00:00 +0100 5665145 http://www.medworm.com/index.php?rid=5658027&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F7%2F1%2F2 Conclusion: Our results suggest that DNMT1 depletion triggers a p14ARF/p53 dependent cell cycle arrest to counteract the aneuploidy induced by changes in DNA methylation. (Source: Cell Division) Cell Division journals http://www.medworm.com/rss/comments.php?id=5658027 Fri, 03 Feb 2012 05:00:00 +0100 5658027 http://www.medworm.com/index.php?rid=5658028&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F7%2F1%2F1 Conclusions: Slt2 is activated by several genotoxic treatments and is required to properly cope with DNA damage. Slt2 function is important for bud morphogenesis and optimal Swe1 degradation under replicative stress. The MAPK Slt2 appears as a new player in the cellular response to genotoxic stresses. (Source: Cell Division) Cell Division journals http://www.medworm.com/rss/comments.php?id=5658028 Wed, 01 Feb 2012 05:00:00 +0100 5658028 http://www.medworm.com/index.php?rid=5550834&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F6%2F1%2F23 Conclusions: Phosphorylation of Cdc5 by Cdk1 is required to maintain Cdc5 levels during G2. However, phosphorylation of T23 (probably by Cdk1) caps Cdc5 and other CLB2 cluster protein accumulation, preventing potential protein toxicity, which may arise from their overexpression or from APC/CCdh1 inactivation. (Source: Cell Division) Cell Division journals http://www.medworm.com/rss/comments.php?id=5550834 Wed, 28 Dec 2011 05:00:00 +0100 5550834 http://www.medworm.com/index.php?rid=5502655&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F6%2F1%2F22 Picture illustrating 3D reconstructions of interphase and mitotic nuclei within a fixed H2B¿HcRed-expressing spheroid. The blue correspond to interphase nuclei and red to mitotic condensed chromosomes. These reconstructions have been obtained from SPIM z-stacks and processed using the VSNR, FIJI and Imaris softwares. (Source: Cell Division) Cell Division journals http://www.medworm.com/rss/comments.php?id=5502655 Mon, 12 Dec 2011 05:00:00 +0100 5502655 http://www.medworm.com/index.php?rid=5493275&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F6%2F1%2F20 The cell cycle is a tightly controlled series of events that ultimately lead to cell division. The literature deciphering the molecular processes involved in regulating the consecutive cell cycle steps is colossal. By contrast, much less is known about non-dividing cellular states, even if they concern the vast majority of cells, from prokaryotes to multi-cellular organisms. Indeed, cells decide to enter the division cycle only if conditions are favourable. Otherwise they may enter quiescence, a reversible non-dividing cellular state. Recent studies in yeast have shed new light on the transition between proliferation and quiescence, re-questioning the notion of cell cycle commitment. They also indicate a predominant role for cellular metabolic status as a major regulator of quiescence esta... Cell Division journals http://www.medworm.com/rss/comments.php?id=5493275 Fri, 09 Dec 2011 05:00:00 +0100 5493275 http://www.medworm.com/index.php?rid=5493274&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F6%2F1%2F21 Maintenance of genomic integrity is essential for cell survival. Specifically, during DNA replication cells use a complex network of mechanisms that prevents genomic instability. Recently, we and others identified Wee1, a serine/threonine and tyrosine- kinase, as a new modulator of the genomic stability during S phase. Loss of its activity causes a general DNA damage response activation and a decrease in replication fork speed. These effects are counteracted by the downregulation of the endonuclease complex Mus81-Eme1, showing a new link between this endonuclease and Wee1 during DNA replication. Here we discuss the function of Wee1 in genomic stability and its relationship with the Mus81-Eme1 complex. (Source: Cell Division) Cell Division journals http://www.medworm.com/rss/comments.php?id=5493274 Fri, 09 Dec 2011 05:00:00 +0100 5493274 http://www.medworm.com/index.php?rid=5398339&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F6%2F1%2F19 Regulation of cytoskeletal remodeling is essential for cell cycle transitions. In fission yeast two NDR kinase signaling cascades, MOR and SIN, regulate the actin cytoskeleton to promote polarized growth during interphase and cytokinesis respectively. Our understanding of how these signaling pathways are coordinated to assist transition between the two cell-cycle stages is limited. Here, we review work from our laboratory, which reveals that cross talk between the SIN and MOR pathways is required for inhibition of interphase polarity programs during cytokinesis. Given the conservation of NDR kinase signaling pathways, our results may define general mechanisms by which these pathways are coordinated in higher organisms. (Source: Cell Division) Cell Division journals http://www.medworm.com/rss/comments.php?id=5398339 Fri, 11 Nov 2011 05:00:00 +0100 5398339 http://www.medworm.com/index.php?rid=5378361&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F6%2F1%2F18 Early studies in lower Eukaryotes have defined a role for the members of the NimA related kinase (Nek) family of protein kinases in cell cycle control. Expansion of the Nek family throughout evolution has been accompanied by their broader involvement in checkpoint regulation and cilia biology. Moreover, mutations of Nek family members have been identified as drivers behind the development of ciliopathies and cancer. Recent advances in studying the physiological roles of Nek family members utilizing mouse genetics and RNAi-mediated knockdown are revealing intricate associations of Nek family members with fundamental biological processes. Here, we aim to provide a comprehensive account of our understanding of Nek kinase biology and their involvement in cell cycle, checkpoint control and canc... Cell Division journals http://www.medworm.com/rss/comments.php?id=5378361 Mon, 31 Oct 2011 04:00:00 +0100 5378361 http://www.medworm.com/index.php?rid=5158309&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F6%2F1%2F17 Conclusions: Distinct forces driving cortical cap protrusion and membrane invagination are involved in spindle rotation and polar body extrusion during meiosis II in mouse oocytes. (Source: Cell Division) Cell Division journals http://www.medworm.com/rss/comments.php?id=5158309 Wed, 24 Aug 2011 23:00:00 +0100 5158309 http://www.medworm.com/index.php?rid=5085849&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F6%2F1%2F16 ${item.shortDescription} (Source: Cell Division) Cell Division journals http://www.medworm.com/rss/comments.php?id=5085849 Sun, 31 Jul 2011 23:00:00 +0100 5085849 http://www.medworm.com/index.php?rid=5019039&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F6%2F1%2F15 Eukaryotic chromatin is a combination of DNA and histone proteins. It is established fact that epigenetic mechanisms are associated with DNA and histones. Initial studies emphasizes on core histones association with DNA, however later studies prove the importance of linker histone H1 epigenetic. There are many types of linker histone H1 found in mammals. These subtypes are cell specific and their amount in different types of cells varies as the cell functions. Many types of post-translational modifications which occur on different residues in each subtype of linker histone H1 induce conformational changes and allow the different subtypes of linker histone H1 to interact with chromatin at different stages during cell cycle which results in the regulation of transcription and gene expression... Cell Division journals http://www.medworm.com/rss/comments.php?id=5019039 Mon, 11 Jul 2011 23:00:00 +0100 5019039 http://www.medworm.com/index.php?rid=4933603&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F6%2F1%2F14 This study suggests that most of the compounds from the roots of D. versipellis could inhibit the growth of human carcinoma cells. In addition, PTO and DDPT could induce apoptosis of tumor cells. (Source: Cell Division) Cell Division journals http://www.medworm.com/rss/comments.php?id=4933603 Tue, 14 Jun 2011 23:00:00 +0100 4933603 http://www.medworm.com/index.php?rid=4911232&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F6%2F1%2F13 Conclusions: Our data suggests large Gcn5 and Hda1 containing complexes may compete for space on promoters that utilize the Ssn6/Tup1 repressor complex. We predict that in apc5CA cells the accumulation of an APC target may compensate for the loss of both GCN5 and HDA1. (Source: Cell Division) Cell Division journals http://www.medworm.com/rss/comments.php?id=4911232 Tue, 07 Jun 2011 23:00:00 +0100 4911232 http://www.medworm.com/index.php?rid=4902064&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F6%2F1%2F12 For proper tissue morphogenesis, cell divisions and cell fate decisions must be tightly and coordinately regulated. One elegant way to accomplish this is to couple them with asymmetric cell divisions. Progenitor cells in the developing epidermis undergo both symmetric and asymmetric cell divisions to balance surface area growth with the generation of differentiated cell layers. Here we review the molecular machinery implicated in controlling asymmetric cell division. In addition, we discuss the ability of epidermal progenitors to choose between symmetric and asymmetric divisions and the key regulatory points that control this decision. (Source: Cell Division) Cell Division journals http://www.medworm.com/rss/comments.php?id=4902064 Sun, 05 Jun 2011 23:00:00 +0100 4902064 http://www.medworm.com/index.php?rid=4802093&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F6%2F1%2F10 The vast majority of cells, from prokaryotes up to vertebrate organisms, spend most of their time in quiescence, a state defined as a temporary and reversible absence of proliferation. Establishing the quiescent state while maintaining the capacity to re-enter the proliferation cycle are critical for cell survival and must be tightly orchestrated to avoid pathological proliferation. Hence, studying the biology of quiescent cells is an exciting research field. Taking advantage of technical progress in genomic, transcriptomic and metabolomic, the nature of transitions between proliferation and quiescence have been recently re-visited in budding yeast. Together with new findings in cell biology, these studies resuscitate an old demon in the field: the controversial existence of a "quiescence ... Cell Division journals http://www.medworm.com/rss/comments.php?id=4802093 Sun, 08 May 2011 23:00:00 +0100 4802093 http://www.medworm.com/index.php?rid=4802092&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F6%2F1%2F11 The centromere is a specialized chromosomal region that directs the formation of the kinetochore, a huge protein assembly that acts as the attachment site for spindle microtubules and carries out chromosome movement during cell division. Centromere loss or the presence of extra centromeres adversely affect chromosome segregation and may result in aneuploidy, a condition found in many human tumors and a major cause of miscarriages and birth defects. Consequently, understanding the basis of centromere determination and propagation is of great relevance to both fundamental and clinical research. In recent years, it has become clear that centromeres are defined by the presence of a histone H3 variant known as Centromere Protein A, CENP-A, or CenH3. Much effort has been devoted to understanding... Cell Division journals http://www.medworm.com/rss/comments.php?id=4802092 Sun, 08 May 2011 23:00:00 +0100 4802092 http://www.medworm.com/index.php?rid=4714594&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F6%2F1%2F9 The Mps1 protein kinase is an intriguing and controversial player in centriole assembly. Originally shown to control duplication of the budding yeast spindle pole body, Mps1 is present in eukaryotes from yeast to humans, the nematode C. elegans being a notable exception, and has also been shown to regulate the spindle checkpoint and an increasing number of cellular functions relating to genomic stability. While its function in the spindle checkpoint appears to be both universally conserved and essential in most organisms, conservation of its originally described function in spindle pole duplication has proven controversial, and it is less clear whether Mps1 is essential for centrosome duplication outside of budding yeast. Recent studies of Mps1 have identified at least two distinct functio... Cell Division journals http://www.medworm.com/rss/comments.php?id=4714594 Wed, 13 Apr 2011 23:00:00 +0100 4714594 http://www.medworm.com/index.php?rid=4693115&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F6%2F1%2F8 Conclusions: The basic features of the anaphase B switch, involving the suppression of poleward flux and reorganization of growing microtubule plus ends, is conserved in these systems. Thus S2 cells may be useful for rapidly identifying novel components of this switch. The quantitative differences likely reflect the adaptation of embryonic spindles for rapid, streamlined mitoses. (Source: Cell Division) Cell Division journals http://www.medworm.com/rss/comments.php?id=4693115 Thu, 07 Apr 2011 23:00:00 +0100 4693115 http://www.medworm.com/index.php?rid=4663781&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F6%2F1%2F7 Conclusions: The catalytic motif replacement compromises polyubiquitination activity of Cdc34 and alters its regulation in vitro and in vivo, but either motif can support Cdc34 function in yeast viability. Robust polyubiquitination mediated by the S73/S97/loop motif is thus not necessary for Cdc34 role in yeast viability, at least under typical laboratory conditions. (Source: Cell Division) Cell Division journals http://www.medworm.com/rss/comments.php?id=4663781 Wed, 30 Mar 2011 23:00:00 +0100 4663781 http://www.medworm.com/index.php?rid=4531951&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F6%2F1%2F6 Nuage (or commonly known as chromatoid body in mammals) is a conserved germline-specific organelle that has been linked to the Piwi-interacting RNA (piRNA) pathway. piRNAs are a class of gonadal-specific RNAs that are ~23-29 nucleotides in length and protect genome stability by repressing the expression of deleterious retrotransposons. More recent studies in Drosophila have implicated the piRNA pathway in other functions including canalization of embryonic development, regulation of maternal gene expression and telomere protection. We have recently shown that Vasa (known as Mouse Vasa Homolog in mouse), a nuage component, plays a mitotic role in promoting chromosome condensation and segregation by facilitating robust chromosomal localization of condensin I in the Drosophila germline. Vasa ... Cell Division journals http://www.medworm.com/rss/comments.php?id=4531951 Mon, 28 Feb 2011 00:00:00 +0100 4531951 http://www.medworm.com/index.php?rid=4464373&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F6%2F1%2F5 Regulation of cyclin levels is important for many cell cycle-related processes and can occur at several different steps of gene expression. Translational regulation of cyclins, which occurs by a variety of regulatory mechanisms, permits a prompt response to signal transduction pathways induced by environmental stimuli. This review will summarize translational control of cyclins and its influence on cell cycle progression. (Source: Cell Division) Cell Division journals http://www.medworm.com/rss/comments.php?id=4464373 Fri, 11 Feb 2011 00:00:00 +0100 4464373 http://www.medworm.com/index.php?rid=4459652&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F6%2F1%2F4 Conclusions: These data suggest that the DSG motif, in addition to its function in Cdc25A-mediated degradation, plays a role in cell survival during early embyogenesis through suppression of ASK1-mediated apoptosis. (Source: Cell Division) Cell Division journals http://www.medworm.com/rss/comments.php?id=4459652 Thu, 10 Feb 2011 00:00:00 +0100 4459652 http://www.medworm.com/index.php?rid=4428808&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F6%2F1%2F3 Inactivation of the gene encoding the adenomatous polyposis coli (APC) tumour suppressor protein is recognized as the key early event in the development of colorectal cancers (CRC). Apc loss leads to nuclear localization of beta-catenin and constitutive activity of the beta-catenin-Tcf4 transcription complex. This complex drives the expression of genes involved in cell cycle progression such as c-Myc and cyclin D2. Acute loss of Apc in the small intestine leads to hyperproliferation within the intestinal crypt, increased levels of apoptosis, and perturbed differentiation and migration. It has been demonstrated that c-Myc is a critical mediator of the phenotypic abnormalities that follow Apc loss in the intestine. As it may be difficult to pharmacologically inhibit transcription factors suc... Cell Division journals http://www.medworm.com/rss/comments.php?id=4428808 Wed, 02 Feb 2011 00:00:00 +0100 4428808 http://www.medworm.com/index.php?rid=4405498&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F6%2F1%2F2 Because centrosome amplification generates aneuploidy and since centrosome amplification is ubiquitous in human tumors, a strong case is made for centrosome amplification being a major force in tumor biogenesis. Various evidence showing that oncogenes and altered tumor suppressors lead to centrosome amplification and aneuploidy suggests that oncogenes and altered tumor suppressors are a major source of genomic instability in tumors, and that they generate those abnormal processes to initiate and sustain tumorigenesis. We discuss how altered tumor suppressors and oncogenes utilize the cell cycle regulatory machinery to signal centrosome amplification and aneuploidy. (Source: Cell Division) Cell Division journals http://www.medworm.com/rss/comments.php?id=4405498 Thu, 27 Jan 2011 00:00:00 +0100 4405498 http://www.medworm.com/index.php?rid=4382558&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F6%2F1%2F1 The Skp2 locus encodes two proteins, Skp2 and Skp2B. The role of Skp2 in the ubiquitin-dependent degradation of key regulators of the retinoblastoma protein pathway has been well established. More recent work from the McCormick's group suggested that Skp2 has an ubiquitin-independent function in the regulation of the p53 pathway. Adding to this observation, we reported that Skp2B also regulates the activity of p53 by degrading a distinct substrate, prohibitin. Since prohibitin has been implicated in the regulation of the Rb pathway, collectively, these observations suggest that Skp2 and Skp2B team up against p53 and Rb. (Source: Cell Division) Cell Division journals http://www.medworm.com/rss/comments.php?id=4382558 Fri, 21 Jan 2011 00:00:00 +0100 4382558 http://www.medworm.com/index.php?rid=4189957&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F5%2F1%2F27 Conclusions: The present observations suggest that human Fbw7 ubiquitylates human c-Myb in a CPD-independent manner, whereas mouse Fbw7 ubiquitylates human c-Myb in a CPD-dependent manner. Moreover, GSK3 negatively regulates the transcriptional expression of human c-Myb but does not promote Fbw7-dependent degradation of human c-Myb protein. Inactivation of GSK3 as well as mutations of Fbw7 may be causes of the enhanced c-Myb expression observed in leukemia cells. We conclude that expression levels of human and mouse c-Myb are regulated via different mechanisms. (Source: Cell Division) Cell Division journals http://www.medworm.com/rss/comments.php?id=4189957 Sun, 21 Nov 2010 00:00:00 +0100 4189957 http://www.medworm.com/index.php?rid=4081912&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F5%2F1%2F26 c-Jun activation domain-binding protein-1 (Jab1) acts as a modulator of intracellular signaling and affects cellular proliferation and apoptosis, through its existence as a monomer or as the fifth component of the constitutive photomorphogenic-9 signalosome (CSN5). Jab1/CSN5 is involved in transcription factor specificity, deneddylation of NEDD8, and nuclear-to-cytoplasmic shuttling of key molecules. Jab1/CSN5 activities positively and negatively affect a number of pathways, including integrin signaling, cell cycle control, and apoptosis. Also, more recent studies have demonstrated the intriguing roles of Jab1 in regulating genomic instability and DNA repair. The effects of Jab1/CSN5's multiple protein interactions are generally oncogenic in nature, and overexpression of Jab1/CSN5 in cance... Cell Division journals http://www.medworm.com/rss/comments.php?id=4081912 Sun, 17 Oct 2010 23:00:00 +0100 4081912 http://www.medworm.com/index.php?rid=4012816&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F5%2F1%2F25 Polo-like kinase 4 (PLK4) is a unique member of the Polo-like family of kinases that shares little homology with its siblings and has an essential role in centriole duplication. The turn-over of this kinase must be strictly controlled to prevent centriole amplification. This is achieved, in part, by an autoregulatory mechanism, whereby PLK4 autophosphorylates residues in a PEST sequence located carboxy-terminal to its catalytic domain. Phosphorylated PLK4 is subsequently recognized by the SCF complex, ubiquitinylated and targeted to the proteasome for degradation. Recent data have also shown that active PLK4 is restricted to the centrosome, a mechanism that could serve to prevent aberrant centriole assembly elsewhere in the cell. While significant advances have been made in understanding h... Cell Division journals http://www.medworm.com/rss/comments.php?id=4012816 Tue, 28 Sep 2010 23:00:00 +0100 4012816 http://www.medworm.com/index.php?rid=3968863&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F5%2F1%2F24 Mutations in the human gene coding for XPD lead to segmental progeria - the premature appearance of some of the phenotypes normally associated with aging - which may or may not be accompanied by increased cancer incidence. XPD is required for at least three different critical cellular functions: in addition to participating in the process of nucleotide excision repair (NER), which removes bulky DNA lesions, XPD also regulates transcription as part of the general transcription factor IIH (TFIIH) and controls cell cycle progression through its interaction with CAK, a pivotal activator of cyclin dependent kinases (CDKs). The study of inherited XPD disorders offers the opportunity to gain insights into the coordination of important cellular events and may shed light on the mechanisms that regu... Cell Division journals http://www.medworm.com/rss/comments.php?id=3968863 Tue, 14 Sep 2010 23:00:00 +0100 3968863 http://www.medworm.com/index.php?rid=3946297&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F5%2F1%2F22 The multi-functional adaptor protein NEDD9/HEF1/Cas-L regulates cell motility, invasion and cell cycle progression, and plays key roles in cancer progression and metastasis. NEDD9 is localized to the centrosome and is required for activation of Aurora A kinase in mitosis. Here we demonstrate that the HECT-WW protein Smurf2 physically associates with NEDD9 and is required for the stability of NEDD9 protein. Smurf2 depletion results in a marked decrease in NEDD9 protein levels, by facilitating polyubiquitination and proteasomal degradation of NEDD9. Conversely forced overexpression of Smurf2 results in upregulation of endogenous NEDD9 protein, confirming the role for Smurf2 in NEDD9 stability. Cells with Smurf2 depletion fail to activate Aurora A at the G2/M boundary, leading to a marked del... Cell Division journals http://www.medworm.com/rss/comments.php?id=3946297 Tue, 07 Sep 2010 23:00:00 +0100 3946297 http://www.medworm.com/index.php?rid=3929114&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F5%2F1%2F21 The role of Chk1 in the cellular response to DNA replication stress is well established. However recent work indicates a novel role for Chk1 in the suppression of apoptosis following the disruption of DNA replication or DNA damage. This review will consider these findings in the context of known pathways of Chk1 signalling and potential applications of therapies that target Chk1. (Source: Cell Division) Cell Division journals http://www.medworm.com/rss/comments.php?id=3929114 Wed, 01 Sep 2010 23:00:00 +0100 3929114 http://www.medworm.com/index.php?rid=3911491&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F5%2F1%2F20 In fission yeast the intra-S phase and DNA damage checkpoints are activated in response to inhibition of DNA replication or DNA damage, respectively. The intra-S phase checkpoint responds to stalled replication forks leading to the activation of the Cds1 kinase that both delays cell cycle progression and stabilizes DNA replication forks. The DNA damage checkpoint, that operates during the G2 phase of the cell cycle delays mitotic progression through activation of the checkpoint kinase, Chk1. Delay of the cell cycle is believed to be essential to allow time for either replication restart (in S phase) or DNA damage repair (in G2). Previously, our laboratory showed that fission yeast cells deleted for the N-terminal half of DNA polymerase epsilon (Cdc20) are delayed in S phase, but surprising... Cell Division journals http://www.medworm.com/rss/comments.php?id=3911491 Thu, 26 Aug 2010 23:00:00 +0100 3911491 http://www.medworm.com/index.php?rid=3861821&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F5%2F1%2F19 Ubiquitination involves the attachment of ubiquitin to lysine residues on substrate proteins or itself, which can result in protein monoubiquitination or polyubiquitination. Ubiquitin attachment to different lysine residues can generate diverse substrate-ubiquitin structures, targeting proteins to different fates. The mechanisms of lysine selection are not well understood. Ubiquitination by the largest group of E3 ligases, the RING-family E3s, is catalyzed through co-operation between the non-catalytic ubiquitin-ligase (E3) and the ubiquitin-conjugating enzyme (E2), where the RING E3 binds the substrate and the E2 catalyzes ubiquitin transfer. Previous studies suggest that ubiquitination sites are selected by E3-mediated positioning of the lysine toward the E2 active site. Ultimately, at a... Cell Division journals http://www.medworm.com/rss/comments.php?id=3861821 Thu, 12 Aug 2010 23:00:00 +0100 3861821 http://www.medworm.com/index.php?rid=3729742&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F5%2F1%2F18 In many eukaryotes, histone gene expression is regulated in a cell cycle-dependent manner, with a spike pattern at S phase. In fission yeast the GATA-type transcription factor Ams2 is required for transcriptional activation of all the core histone genes during S phase and Ams2 protein levels per se show concomitant periodic patterns. We have recently unveiled the molecular mechanisms underlying Ams2 fluctuation during the cell cycle. We have found that Ams2 stability varies during the cell cycle, and that the ubiquitin-proteasome pathway is responsible for Ams2 instability. Intriguingly, Ams2 proteolysis requires Hsk1-a Cdc7 homologue in fission yeast generally called Dbf4-dependent protein kinase (DDK)-and the SCF ubiquitin ligase containing the substrate receptor Pof3 F-box protein. Here... Cell Division journals http://www.medworm.com/rss/comments.php?id=3729742 Tue, 06 Jul 2010 23:00:00 +0100 3729742 http://www.medworm.com/index.php?rid=3729743&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F5%2F1%2F17 Conclusions: Our software solution, Circadian Gene Express (CGE), is easy to use and allows precise and semi-automatic tracking of moving cells over longer period of time. In spite of significant circadian variations in protein expression with extremely low expression levels at the valley phase, CGE allows accurate and efficient recording of large number of cell parameters, including level of reporter protein expression, velocity, direction of movement, and others. CGE proves to be useful for the analysis of widefield fluorescent microscopy datasets, as well as for bioluminescence imaging. Moreover, it might be easily adaptable for confocal image analysis by manually choosing one of the focal planes of each z-stack of the various time points of a time series.AvailabilityCGE is a Java plugi... Cell Division journals http://www.medworm.com/rss/comments.php?id=3729743 Mon, 05 Jul 2010 23:00:00 +0100 3729743 http://www.medworm.com/index.php?rid=3686960&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F5%2F1%2F16 Conclusions: In addition to the previously defined differences between mouse and human cells in the mechanisms and phenotypes associated with senescence, we conclude that senescent mouse and human fibroblasts also differ at the level of chromatin and the signaling pathways used to regulate chromatin. These differences between human and mouse senescence may contribute to the increased propensity of mouse fibroblasts (and perhaps other mouse cell types) to become immortalized and transformed, compared to human cells. (Source: Cell Division) Cell Division journals http://www.medworm.com/rss/comments.php?id=3686960 Mon, 21 Jun 2010 23:00:00 +0100 3686960 http://www.medworm.com/index.php?rid=3581463&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F5%2F1%2F15 Recent data show that cells from many cancers exhibit massive chromosome instability. The traditional view is that the gradual accumulation of mutations in genes involved in transcriptional regulation and cell cycle controls results in tumor development. This, however, does not exclude the possibility that some mutations could be more potent than others in destabilizing the genome by targeting both chromosomal integrity and corresponding checkpoint mechanisms simultaneously. Three such examples of "single-hit" lesions potentially leading to heritable genome destabilization are discussed. They include: failure to release sister chromatid cohesion due to the incomplete proteolytic cleavage of cohesin; massive merotelic kinetochore misattachments upon condensin depletion; and chromosome under... Cell Division journals http://www.medworm.com/rss/comments.php?id=3581463 Tue, 18 May 2010 23:00:00 +0100 3581463 http://www.medworm.com/index.php?rid=3569677&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F5%2F1%2F13 Although the large majority of solid tumors show a combination of mitotic spindle defects and chromosomal instability, little is known about the mechanisms that govern the initial steps in tumorigenesis. The recent report of spindle-induced DNA damage provides evidence for a single mechanism responsible for the most prominent genetic defects in chromosomal instability. Spindle-induced DNA damage is brought about by uncorrected merotelic attachments, which cause kinetochore distortion, chromosome breakage at the centromere, and possible activation of DNA damage repair pathways. Although merotelic attachments are common early in mitosis, some escape detection by the kinetochore pathway. As a consequence, a proportion of merotelic attachments gives rise to chromosome breakage in normal cells ... Cell Division journals http://www.medworm.com/rss/comments.php?id=3569677 Sun, 16 May 2010 23:00:00 +0100 3569677 http://www.medworm.com/index.php?rid=3569676&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F5%2F1%2F14 Inflammation is an important environmental factor that promotes tumourigenesis and the progression of established cancerous lesions, and recent studies have started to dissect the mechanisms linking the two pathologies. These inflammatory and infectious conditions trigger immune cell release of soluble mediators which facilitate survival and proliferation of tumour cells in a paracrine manner. In addition, (epi-)genetic mutations affecting oncogenes, tumour-suppressor genes, chromosomal rearrangements and amplifications trigger the release of inflammatory mediators within the tumour microenvironment to promote neoplastic growth in an autocrine manner. These two pathways converge in tumour cells and result in activation of the latent signal transducer and activator of transcription 3 (STAT3... Cell Division journals http://www.medworm.com/rss/comments.php?id=3569676 Sun, 16 May 2010 23:00:00 +0100 3569676 http://www.medworm.com/index.php?rid=3560046&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F5%2F1%2F10 Conclusions: The expression pattern of human eIF3f during the cell cycle confirms that this gene is cell division related. The fact that eIF3f expression peaks in two cell cycle phases raises the possibility that this gene may exert a differential function in the S and M phases. Our results strongly suggest that eIF3f is essential for cell proliferation. (Source: Cell Division) Cell Division journals http://www.medworm.com/rss/comments.php?id=3560046 Wed, 12 May 2010 23:00:00 +0100 3560046 http://www.medworm.com/index.php?rid=3560045&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F5%2F1%2F11 The cyclin dependent kinase Cdk1 controls the cell cycle, which is best understood in the model organism S. cerevisiae. Research performed during the past decade has significantly improved our understanding of the molecular machinery of the cell cycle. Approximately 75 targets of Cdk1 have been identified that control critical cell cycle events, such as DNA replication and segregation, transcriptional programs and cell morphogenesis. In this review we discuss currently known targets of Cdk1 in the budding yeast S. cerevisiae and highlight the role of Cdk1 in several crucial processes including maintenance of genome stability. (Source: Cell Division) Cell Division journals http://www.medworm.com/rss/comments.php?id=3560045 Wed, 12 May 2010 23:00:00 +0100 3560045 http://www.medworm.com/index.php?rid=3560044&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F5%2F1%2F12 The kinase Wee1 has been recognized for a quarter century as a key inhibitor of Cyclin dependent kinase 1 (Cdk1) and mitotic entry in eukaryotes. Nonetheless, Wee1 regulation is not well understood and its large amino-terminal regulatory domain (NRD) has remained largely uncharted. Evidence has accumulated that cyclin B/Cdk1 complexes reciprocally inhibit Wee1 activity through NRD phosphorylation. Recent studies have identified the first functional NRD elements and suggested that vertebrate cyclin A/Cdk2 complexes also phosphorylate the NRD. A short NRD peptide, termed the Wee box, augments the activity of the Wee1 kinase domain. Cdk1/2-mediated phosphorylation of the Wee box (on T239) antagonizes kinase activity. A nearby region harbors a conserved RxL motif (RxL1) that promotes cyclin A/... Cell Division journals http://www.medworm.com/rss/comments.php?id=3560044 Wed, 12 May 2010 23:00:00 +0100 3560044 http://www.medworm.com/index.php?rid=3350132&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F5%2F1%2F8 Maintenance of genomic integrity is important for cellular viability and proliferation. During DNA replication, cells respond to replication stress by activating checkpoint pathways that stabilize replication forks and prevent cell cycle progression. The Saccharomyces cerevisiae F-box protein Dia2 is a ubiquitin ligase component required for genomic stability and may help replication complexes negotiate damaged DNA or natural fragile sites. We recently implicated Dia2 in the replication stress response. We demonstrated that Dia2 is targeted for ubiquitin-mediated proteolysis and that activation of the S-phase checkpoint inhibits Dia2 protein turnover. S-phase checkpoint mutants fail to stabilize the Dia2 protein and checkpoint mutants that lack Dia2 exhibit increased sensitivity to replica... Cell Division journals http://www.medworm.com/rss/comments.php?id=3350132 Wed, 10 Mar 2010 00:00:00 +0100 3350132 http://www.medworm.com/index.php?rid=3302181&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F5%2F1%2F7 Regulation of the repair of DNA double-strand breaks by homologous recombination is extremely important for both cell viability and the maintenance of genomic integrity. Modulation of double-strand break repair in the yeast Saccharomyces cerevisiae involves controlling the recruitment of one of the central recombination proteins, Rad52, to sites of DNA lesions. The Rad52 protein, which plays a role in strand exchange and the annealing of single strand DNA, is positively regulated upon entry into S phase, repressed during the intra-S phase checkpoint, and undergoes posttranslational modification events such as phosphorylation and sumoylation. These processes all contribute to the timing of Rad52 recruitment, its stability and function. Here, we summarize the regulatory events affecting the ... Cell Division journals http://www.medworm.com/rss/comments.php?id=3302181 Tue, 23 Feb 2010 00:00:00 +0100 3302181 http://www.medworm.com/index.php?rid=3243558&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F5%2F1%2F6 Pancreatic beta-cells are metabolic sensors involved in the control of glucose homeostasis. This particular cell type controls insulin secretion through a fine-tuned process, which dregulation have important pathological consequences, such as observed during type 2 diabetes. We recently implicated E2F1 in the control of glucose homeostasis. First we showed that E2f1-/- mice have decreased pancreatic size, as the result of impaired postnatal pancreatic growth. We observed in this study that E2F1 was highly expressed in non-proliferating pancreatic beta-cells, suggesting that E2F1, besides the control of beta-cell number could have a role in pancreatic beta-cell function. We demonstrate in our recent study, both in vitro and in vivo that E2F1directly regulates the expression of Kir6.2, a key... Cell Division journals http://www.medworm.com/rss/comments.php?id=3243558 Fri, 05 Feb 2010 00:00:00 +0100 3243558 http://www.medworm.com/index.php?rid=3220296&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F5%2F1%2F5 Gradients are used in a number of biological systems to transmit spatial information over a range of distances. The best studied are morphogen gradients where information is transmitted over many cell lengths. Smaller mitotic gradients reflect the need to organize several distinct events along the length of the mitotic spindle. The intracellular gradients that characterize mitosis are emerging as important regulatory paradigms. Intracellular gradients utilize intrinsic auto-regulatory feedback loops and diffusion to establish stable regions of activity within the mitotic cytosol. We review three recently described intracellular mitotic gradients. The Ran GTP gradient with its elaborate cascade of nuclear transport receptors and cargoes is the best characterized, yet the dynamics underlying... Cell Division journals http://www.medworm.com/rss/comments.php?id=3220296 Fri, 29 Jan 2010 00:00:00 +0100 3220296 http://www.medworm.com/index.php?rid=3193594&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F5%2F1%2F4 Senescence and mitotic catastrophe (MC) are two distinct crucial non-apoptotic mechanisms, often triggered in cancer cells and tissues in response to anti-cancer drugs. Chemotherapeuticals and myriad other factors induce cell eradication via these routes. While senescence drives the cells to a state of quiescence, MC drives the cells towards death during the course of mitosis. The senescent phenotype distinguishes tumor cells that survived drug exposure but lost the ability to form colonies from those that recover and proliferate after treatment. Although senescent cells do not proliferate, they are metabolically active and may secrete proteins with potential tumor-promoting activities. The other anti-proliferative response of tumor cells is MC that is a form of cell death that results fro... Cell Division journals http://www.medworm.com/rss/comments.php?id=3193594 Thu, 21 Jan 2010 00:00:00 +0100 3193594 http://www.medworm.com/index.php?rid=3185192&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F5%2F1%2F3 Apoptosis induced by DNA damage is an important mechanism of tumor suppression and it is significant also in cancer chemotherapy. Mammalian cells activate the pathways of p53 to induce apoptosis of cells harboring irreparable DNA damages. While p53 induces expression of various pro-apoptotic genes and directly participates in the disruption of mitochondrial membrane polarization, it also increases expression of the cell cycle inhibitor p21 that is a dominant inhibitor of caspase-activation and apoptosis. Here we discuss how Damaged-DNA Binding Protein-2 (DDB2) subdues the level of p21 in cells harboring irreparable DNA damage to support activation of the caspases. We speculate a model in which DDB2 detects and couples the presence of un-repaired DNA damages to the proteolysis of p21, leadi... Cell Division journals http://www.medworm.com/rss/comments.php?id=3185192 Tue, 19 Jan 2010 00:00:00 +0100 3185192 http://www.medworm.com/index.php?rid=3171702&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F5%2F1%2F1 Oncogenic proliferative signals are coupled to a variety of growth inhibitory processes. In cultured primary human fibroblasts, for example, ectopic expression of oncogenic Ras or its downstream mediator initiates cellular senescence, the state of irreversible cell cycle arrest, through up-regulation of cyclin-dependent kinase (CDK) inhibitors, such as p16INK4a. To date, much of our current knowledge of how human p16INK4a gene expression is induced by oncogenic stimuli derives from studies undertaken in cultured primary cells. However, since human p16INK4a gene expression is also induced by tissue culture-imposed stress, it remains unclear whether the induction of human p16INK4a gene expression in tissue-cultured cells truly reflects an anti-cancer process or is an artifact of tissue cultu... Cell Division journals http://www.medworm.com/rss/comments.php?id=3171702 Thu, 14 Jan 2010 00:00:00 +0100 3171702 http://www.medworm.com/index.php?rid=2939136&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F4%2F1%2F20 Cancer is a multifaceted disease that results from dysregulated normal cellular signaling networks caused by genetic, genomic and epigenetic alterations at cell or tissue levels. Uncovering the underlying protein signaling network changes, including cell cycle gene networks in cancer, aids in understanding the molecular mechanism of carcinogenesis and identifies the characteristic signaling network signatures unique for different cancers and specific cancer subtypes. The identified signatures can be used for cancer diagnosis, prognosis, and personalized treatment. During the past several decades, the available technology to study signaling networks has significantly evolved to include such platforms as genomic microarray (expression array, SNP array, CGH array, etc.) and proteomic analysis... Cell Division journals http://www.medworm.com/rss/comments.php?id=2939136 Wed, 28 Oct 2009 00:00:00 +0100 2939136 http://www.medworm.com/index.php?rid=2757535&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F4%2F1%2F19 Regulation of gene expression is essential to all aspects of physiological processes in single-cell as well as multicellular organisms. It gives ultimately cells the ability to efficiently respond to extra- and intracellular stimuli participating in cell cycle, growth, differentiation and survival. Regulation of gene expression is executed primarily at the level of transcription of specific mRNAs by RNA polymerase II (RNAPII), typically in several distinct phases. Among them, transcription elongation is positively regulated by the positive transcription elongation factor b (P-TEFb), consisting of CDK9 and cyclin T1, T2 or K. P-TEFb enables transition from abortive to productive transcription elongation by phosphorylating carboxyl-terminal domain (CTD) in RNAPII and negative transcription e... Cell Division journals http://www.medworm.com/rss/comments.php?id=2757535 Tue, 01 Sep 2009 23:00:00 +0100 2757535 http://www.medworm.com/index.php?rid=2737525&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F4%2F1%2F18 During division, certain cellular contents can be distributed unequally; daughter cells with different fates have different needs. Septins are proteins that participate in the establishment and maintenance of asymmetry during cell morphogenesis, thereby contributing to the unequal partitioning of cellular contents during division. The septins themselves provide a paradigm for studying how elaborate multi-component structures are assembled, dynamically modified, and segregated through each cell division cycle and during development. Here we review our current understanding of the supramolecular organization of septins, the function of septins in cellular compartmentalization, and the mechanisms that control assembly, dynamics, and inheritance of higher-order septin structures, with particul... Cell Division journals http://www.medworm.com/rss/comments.php?id=2737525 Tue, 25 Aug 2009 23:00:00 +0100 2737525 http://www.medworm.com/index.php?rid=2678497&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F4%2F1%2F16 RBX1 (also known as ROC1) is a RING subunit of SCF (Skp1, Cullins, F-box proteins) E3 ubiquitin ligases, required for SCF to direct a timely degradation of diverse substrates, thereby regulating numerous cellular processes under both physiological and pathological conditions. Previous studies have shown that RBX1 is essential for growth in yeast, Caenorhabditis elegans and Drosophila. The role of RBX1 in mouse development and in regulation of cancer cell survival was unknown. Our recent work demonstrated that RBX1 is an essential gene for mouse embryogenesis, and targeted disruption of RBX1 causes embryonic lethality at E7.5 due to hypoproliferation as a result of p27 accumulation. We also showed that RBX1 is overexpressed in a number of human cancers, and siRNA silencing of RBX1 caused ca... Cell Division journals http://www.medworm.com/rss/comments.php?id=2678497 Wed, 05 Aug 2009 23:00:00 +0100 2678497 http://www.medworm.com/index.php?rid=2576356&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F4%2F1%2F14 The execution of the mitotic program with high fidelity is dependent upon precise spatiotemporal regulation of posttranslational protein modifications. For example, the timely polyubiquitination of critical mitotic regulators by APC/C is essential for the metaphase to anaphase transition and mitotic exit. The spindle assembly checkpoint prevents unscheduled activity of APC/C-Cdc20 in early mitosis, allowing bipolar attachment of kinetochores to mitotic spindle and facilitating equal segregation of sister chromatids. The critical effector of the spindle checkpoint, Mad2, is recruited to unattached kinetochores forming a complex with other regulatory proteins to efficiently and cooperatively inhibit APC/C-Cdc20. A weakened and/or dysfunctional spindle checkpoint has been linked to the deve... Cell Division journals http://www.medworm.com/rss/comments.php?id=2576356 Mon, 06 Jul 2009 23:00:00 +0100 2576356 http://www.medworm.com/index.php?rid=2570035&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F4%2F1%2F13 Cells slow replication in response to DNA damage. This slowing was the first DNA damage checkpoint response discovered and its study led to the discovery of the central checkpoint kinase, Ataxia Telangiectasia mutated (ATM). Nonetheless, the manner by which the S-phase DNA damage checkpoint slows replication is still unclear. The checkpoint could slow bulk replication by inhibiting replication origin firing or slowing replication fork progression, and both mechanisms appear to be used. However, assays in various systems using different DNA damaging agents have produced conflicting results as to the relative importance of the two mechanisms. Furthermore, although progress has been made in elucidating the mechanism of origin regulation in vertebrates, the mechanism by which forks are slowed ... Cell Division journals http://www.medworm.com/rss/comments.php?id=2570035 Thu, 02 Jul 2009 23:00:00 +0100 2570035 http://www.medworm.com/index.php?rid=2560897&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F4%2F1%2F12 Conclusions: The dynamic balance between Cks1- and Swe1-dependent regulation of Cdc28 and, thereby, the timing of mitosis during yeast dimorphism is regulated in part by Ras2/cAMP-mediated PKA signaling, a key pathway controlling filamentous growth. (Source: Cell Division) Cell Division journals http://www.medworm.com/rss/comments.php?id=2560897 Tue, 30 Jun 2009 23:00:00 +0100 2560897 http://www.medworm.com/index.php?rid=2508637&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F4%2F1%2F11 Skp2 over-expression has been observed in many human cancers. However, the mechanisms underlying elevated Skp2 expression have remained elusive. We recently reported that Akt1, but not Akt2, directly controls Skp2 stability by interfering with its association with APC/Cdh1. As a result, Skp2 degradation is protected in cancer cells with elevated Akt activity. This finding expands our knowledge of how specific kinase cascades influence proteolysis governed by APC/Cdh1 complexes. However, it awaits further investigation to elucidate whether the PI3K/Akt circuit affects other APC/Cdh1 substrates. Our results further strengthen the argument that different Akt isoforms might have distinct, even opposing functions in the regulation of cell growth or migration. In addition, we reported that Ser72... Cell Division journals http://www.medworm.com/rss/comments.php?id=2508637 Mon, 22 Jun 2009 23:00:00 +0100 2508637 http://www.medworm.com/index.php?rid=2457383&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F4%2F1%2F10 Cyclin dependent kinases (CDKs) play a central role in the orderly transition from one phase of the eukaryotic mitotic cell division cycle to the next. In this context, p27Kip1 (one of the CIP/KIP family of CDK specific inhibitors in mammals) or its functional analogue in other eukarya prevents a premature transition from G1 to S phase. Recent studies have revealed that expression of a second member of this family, p57Kip2, is induced as trophoblast stem (TS) cells differentiate into trophoblast giant (TG) cells. p57 then inhibits CDK1 activity, an enzyme essential for initiating mitosis, thereby triggering genome endoreduplication (multiple S phases without an intervening mitosis). Expression of p21Cip1, the third member of this family, is also induced in during differentiation of TS cell... Cell Division journals http://www.medworm.com/rss/comments.php?id=2457383 Tue, 02 Jun 2009 04:00:00 +0100 2457383 http://www.medworm.com/index.php?rid=2416198&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F4%2F1%2F9 Once it was believed that Cdk2 was the master regulator of S phase entry. Gene knockout mouse studies of cell cycle regulators revealed that Cdk2 is dispensable for S phase initiation and progression whereby Cdk1 can compensate for the loss of Cdk2. Nevertheless, recent evidence indicates that Cdk2 is involved in cell cycle independent functions such as DNA damage repair. Whether these properties are unique to Cdk2 or also being compensated by other Cdks in the absence of Cdk2 is under extensive investigation. Here we review the emerging new role of Cdk2 in DNA damage repair and also discuss how the loss of Cdk2 impacts the G1/S phase DNA damage checkpoint. (Source: Cell Division) Cell Division journals http://www.medworm.com/rss/comments.php?id=2416198 Mon, 18 May 2009 04:00:00 +0100 2416198 http://www.medworm.com/index.php?rid=2353583&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F4%2F1%2F7 Corepressors are large proteins that facilitate transcriptional repression through recruitment of histone-modifying enzymes. Two major corepressors, SMRT (silencing mediator for retinoid and thyroid hormone receptors) and N-CoR (nuclear receptor corepressor), have been shown to mediate repression associated with nuclear receptors and a myriad of other transcription factors. This review will focus on recent studies on these proteins, including newly discovered physiological roles of the corepressors, their modes of regulation, their roles in antiestrogen-resistant breast cancer and their functions during the cell cycle. (Source: Cell Division) Cell Division journals http://www.medworm.com/rss/comments.php?id=2353583 Tue, 21 Apr 2009 04:00:00 +0100 2353583 http://www.medworm.com/index.php?rid=2301302&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F4%2F1%2F6 Conclusion: DHA elicited prominent chemopreventive effects on its own, and appreciably augmented those of CP as well. The extent of tumor progression in various mouse groups was highly reflected by CRP levels (thus, implying a diagnostic/prognostic role for CRP). Further, this study is the first to reveal that DHA can obliterate the lethal CP-induced nephrotoxicity and renal tissue injury. At the molecular level, DHA appears to act by reducing inflammation, leukocytosis, oxidative stress, and by replenishing the endogenous antioxidant machinery. (Source: Cell Division) Cell Division journals http://www.medworm.com/rss/comments.php?id=2301302 Thu, 02 Apr 2009 04:00:00 +0100 2301302 http://www.medworm.com/index.php?rid=2301304&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F4%2F1%2F5 Conclusions: The microfluidic chip enabled us to acquire the images faster than the conventional method. We speculate that the use of microfluidic chip is effective in acquiring images of large-scale, automated analysis of yeast strains. (Source: Cell Division) Cell Division journals http://www.medworm.com/rss/comments.php?id=2301304 Tue, 24 Mar 2009 04:00:00 +0100 2301304 http://www.medworm.com/index.php?rid=2120904&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F4%2F1%2F3 Metamorphosis of Drosophila involves proliferation, differentiation and death of larval tissues in order to form the adult fly. The major steroid hormone implicated in the larval-pupal transition and adult tissue modelling is ecdysone. Previous reviews have draw together studies connecting ecdysone signaling to the processes of apoptosis and differentiation. Here we discuss those reports connecting the ecdysone pulse to developmentally regulated cell cycle progression. (Source: Cell Division) Cell Division journals http://www.medworm.com/rss/comments.php?id=2120904 Tue, 20 Jan 2009 05:00:00 +0100 2120904 http://www.medworm.com/index.php?rid=1738732&cid=s_34057_171_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F3%2F1%2F11 The yeast SCFMet30 ubiquitin ligase plays a critical role in cell division by regulating the Met4 transcriptional activator of genes that control the uptake and assimilation of sulfur into methionine and S-adenosyl-methionine. The initial view on how SCFMet30 performs its function has been driven by the assumption that SCFMet30 acts exclusively as Met4 inhibitor when high levels of methionine drive an accumulation of cysteine. We revisit this model in light of the growing evidence that SCFMet30 can also activate Met4. The notion that Met4 can be inhibited or activated depending on the sulfur metabolite context is not new, but for the first time both aspects have been linked to SCFMet30, creating an interesting regulatory paradigm in which polyubiquitination and proteolysis of a single tran... Cell Division journals http://www.medworm.com/rss/comments.php?id=1738732 Fri, 25 Jul 2008 04:00:00 +0100 1738732 http://www.medworm.com/index.php?rid=1390817&cid=s_34057_170_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F3%2F1%2F8 Monoubiquitination of H2A is a major histone modification in mammalian cells. Understanding how monoubiquitinated H2A (uH2A) regulates DNA-based processes in the context of chromatin is a challenging question. Work in the past years linked uH2A to transcriptional repression by the Polycomb group proteins of developmental regulators. Recently, a number of mammalian deubiquitinating enzymes (DUBs) that catalyze the removal of ubiquitin from H2A have been discovered. These studies provide convincing evidence that H2A deubiquitination is connected with gene activation. In addition, uH2A regulatory enzymes have crucial roles in the cellular response to DNA damage and in cell cycle progression. In this review we will discuss new insights into uH2A biology, with emphasis on the H2A DUBs. (Source:... Cell Division journals http://www.medworm.com/rss/comments.php?id=1390817 Tue, 22 Apr 2008 04:00:00 +0100 1390817 http://www.medworm.com/index.php?rid=1239147&cid=s_34057_170_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F3%2F1%2F7 Cullin-RING ubiquitin ligases (CRLs) comprise the largest known category of ubiquitin ligases. CRLs regulate an extensive number of dynamic cellular processes, including multiple aspects of the cell cycle, transcription, signal transduction, and development. CRLs are multisubunit complexes composed of a cullin, RING H2 finger protein, a variable substrate-recognition subunit (SRS), and for most CRLs, an adaptor that links the SRS to the complex. Eukaryotic species contain multiple cullins, with five major types in metazoa. Each cullin forms a distinct class of CRL complex, with distinct adaptors and/or substrate-recognition subunits. Despite this diversity, each of the classes of CRL complexes is subject to similar regulatory mechanisms. This review focuses on the global regulation of CRL ... Cell Division journals http://www.medworm.com/rss/comments.php?id=1239147 Mon, 18 Feb 2008 05:00:00 +0100 1239147 http://www.medworm.com/index.php?rid=1199739&cid=s_34057_170_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F3%2F1%2F6 Conclusion: Together, these data suggest that in the C. elegans embryo, HCP-1 interacts with a subset of the spindle checkpoint pathway. Furthermore, the fact that san-1(ok1580);hcp-1(RNAi) animals had a severe viability defect whereas in the san-1(ok1580);hcp-2(RNAi) and san-1(ok1580);hcp-2(ok1757) animals the viability defect was not as severe suggesting that hcp-1 and hcp-2 are not completely redundant. (Source: Cell Division) Cell Division journals http://www.medworm.com/rss/comments.php?id=1199739 Mon, 04 Feb 2008 05:00:00 +0100 1199739 http://www.medworm.com/index.php?rid=1174783&cid=s_34057_170_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F3%2F1%2F5 SUMO proteins are small ubiquitin-like modifiers found in all eukaryotes that become covalently conjugated to other cellular proteins. The SUMO conjugation pathway is biochemically similar to ubiquitin conjugation, although the enzymes within the pathway act exclusively on SUMO proteins. This post-translational modification controls many processes. Here, I will focus on evidence that SUMOylation plays a critical role(s) in mitosis: Early studies showed a genetic requirement for SUMO pathway components in the process of cell division, while later findings implicated SUMOylation in the control of mitotic chromosome structure, cell cycle progression, kinetochore function and cytokinesis. Recent insights into the targets of SUMOylation are likely to be extremely helpful in understanding each o... Cell Division journals http://www.medworm.com/rss/comments.php?id=1174783 Thu, 24 Jan 2008 05:00:00 +0100 1174783 http://www.medworm.com/index.php?rid=1172698&cid=s_34057_170_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F3%2F1%2F4 Mammalian polo-like kinase 1 (Plk1) has been studied extensively as a critical element in regulating various mitotic events during M-phase progression. Plk1 function is spatially regulated through the targeting activity of the conserved polo-box domain (PBD) present in the C-terminal non-catalytic region. Recent progress in our understanding of Plk1 localization to the centromeres shows that Plk1 self-regulates its initial recruitment by phosphorylating a centromeric component PBIP1 and generating its own PBD-binding site. Paradoxically, Plk1 also induces PBIP1 delocalization and degradation from the mitotic kinetochores late in the cell cycle, thus permitting itself to bind to other kinetochore components. Thus, PBIP1-dependent self-recruitment of Plk1 to the interphase centromeres serves... Cell Division journals http://www.medworm.com/rss/comments.php?id=1172698 Wed, 23 Jan 2008 05:00:00 +0100 1172698 http://www.medworm.com/index.php?rid=1169241&cid=s_34057_170_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F3%2F1%2F3 The cell cycle is tightly controlled to ensure that replication origins fire only once per cycle and that consecutive S-phases are separated by mitosis. When controls fail, DNA over-replication ensues: individual origins fire more than once per S-phase (re-replication) or consecutive S-phases occur without intervening mitoses (endoreduplication). In yeast the cell cycle is controlled by a single cyclin dependent kinase (Cdk) that prevents origin licensing at times when it promotes origin firing, and that is inactivated, via proteolysis of its partner cyclin, as cells undergo mitosis. A quantitative model describes three levels of Cdk activity: low activity allows licensing, intermediate activity allows firing but prevents licensing, and high activity promotes mitosis. In higher eukaryotes ... Cell Division journals http://www.medworm.com/rss/comments.php?id=1169241 Tue, 22 Jan 2008 05:00:00 +0100 1169241 http://www.medworm.com/index.php?rid=1149518&cid=s_34057_170_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F3%2F1%2F2 Conclusions: Taken together our results indicate that h14-3-3 gamma can promote abnormal cell proliferation and may act through Cdc25. This has important implications for 14-3-3 gamma as an oncogene as it suggests that elevated levels of 14-3-3 may confer a growth advantage to cells that overexpress it. (Source: Cell Division) Cell Division journals http://www.medworm.com/rss/comments.php?id=1149518 Mon, 14 Jan 2008 05:00:00 +0100 1149518 http://www.medworm.com/index.php?rid=921145&cid=s_34057_170_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F2%2F1%2F29 - (Source: Cell Division) Cell Division journals http://www.medworm.com/rss/comments.php?id=921145 Tue, 02 Oct 2007 04:00:00 +0100 921145 http://www.medworm.com/index.php?rid=875926&cid=s_34057_170_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F2%2F1%2F27 (Source: Cell Division) Cell Division journals http://www.medworm.com/rss/comments.php?id=875926 Mon, 17 Sep 2007 04:00:00 +0100 875926 http://www.medworm.com/index.php?rid=869292&cid=s_34057_170_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F2%2F1%2F26 This article will also discuss the prospects for using this approach to further explore the unknown functions of pRB. (Source: Cell Division) Cell Division journals http://www.medworm.com/rss/comments.php?id=869292 Thu, 13 Sep 2007 04:00:00 +0100 869292 http://www.medworm.com/index.php?rid=820673&cid=s_34057_170_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F2%2F1%2F24 Considerable evidence has accumulated suggesting that cancer has genetic origin, based on the development of genomic alterations, such as deletions, mutations, and/or methylations in critical genes for homeostasis of cellular functions, including cell survival, DNA replication and cell cycle control. Mechanism controlling the precise timing and sequence of cell cycle events as well as checkpoints insuring fidelity of those events are key targets that when disrupted could result in tumorigenesis. Mitosis is the process by which a cell duplicates its genetic information (DNA), in order to generate two, identical, daughter cells. In addition each daughter cell must receive one centrosome and the appropriate complements of cytoplasm and organelles. This process is conventionally divided in to ... Cell Division journals http://www.medworm.com/rss/comments.php?id=820673 Fri, 24 Aug 2007 04:00:00 +0100 820673 http://www.medworm.com/index.php?rid=755519&cid=s_34057_170_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F2%2F1%2F23 During mitosis, the genome duplicated during S-phase is synchronously and accurately segregated to the two daughter cells. The spindle checkpoint prevents premature sister-chromatid separation and mitotic exit. The anaphase-promoting complex/cyclosome (APC/C) is a key target of the spindle checkpoint. Upon checkpoint activation, the mitotic checkpoint complex (MCC) containing Mad2, Bub3, Mad3/BubR1 and Cdc20 inhibits APC/C. Two independent studies in budding yeast have now shed light on the mechanism by which MCC inhibits APC/C. These studies indicate that Mad3 binds to the mitotic activator of APC/C Cdc20 using peptide motifs commonly found in APC/C substrates and thus competes with APC/C substrates for APC/CCdc20 binding. In addition, Mad3 binding to APC/CCdc20 induces Cdc20 ubiquitinati... Cell Division journals http://www.medworm.com/rss/comments.php?id=755519 Tue, 24 Jul 2007 04:00:00 +0100 755519 http://www.medworm.com/index.php?rid=736179&cid=s_34057_170_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F2%2F1%2F21 Che-1 is a RNA polymerase II binding protein involved in the transcriptional regulation of E2F target genes and in cell proliferation. Recently, it has been shown that Che-1 accumulates in cells responding to genotoxic agents such as Doxorubicin and ionizing radiation. The DNA damage-activated checkpoint kinases ATM and Chk2 interact with and phosphorylate Che-1, enhancing its accumulation and stability, and promoting Che-1-mediated transcription of p53-responsive genes and of p53 itself, as evidenced by microarray analysis. This transcriptional response is suppressed by expression of a Che-1 mutant lacking ATM and Chk2 phosphorylation amino acid residues, or by depletion of Che-1 by RNA silencing. In addition, chromatin immunoprecipitation analysis has shown that Che-1 is released from E2... Cell Division journals http://www.medworm.com/rss/comments.php?id=736179 Mon, 16 Jul 2007 04:00:00 +0100 736179 http://www.medworm.com/index.php?rid=672091&cid=s_34057_170_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F2%2F1%2F18 In eukaryotes, DNA replication is strictly regulated so that it occurs only once per cell cycle. The mechanisms that prevent excessive DNA replication are focused on preventing replication origins from being reused within the same cell cycle. This regulation involves the temporal separation of the formation of the pre-replicative complex (pre-RC) from the initiation of DNA replication. The replication licensing factors Cdt1 and Cdc6 recruit the presumptive replicative helicase, the Mcm2-7 complex, to replication origins in late M or G1 phase to form pre-RCs. In fission yeast and metazoa, the Cdt1 licensing factor is degraded at the start of S phase by ubiquitin-mediated proteolysis to prevent the reassembly of pre-RCs. In humans, two E3 complexes, CUL4-DDB1(CDT2) and SCF(Skp2), are redunda... Cell Division journals http://www.medworm.com/rss/comments.php?id=672091 Tue, 12 Jun 2007 04:00:00 +0100 672091 http://www.medworm.com/index.php?rid=660326&cid=s_34057_170_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F2%2F1%2F17 In eukaryotic organisms, chromosomes are spatially organized within the nucleus. Such nuclear architecture provides a physical framework for the genetic activities of chromosomes, and changes its functional organization as the cell moves through the phases of the cell cycle. The fission yeast Schizosaccharomyces pombe provides a striking example of nuclear reorganization during the transition from mitosis to meiosis. In this organism, centromeres remain clustered at the spindle-pole body (SPB; a centrosome-equivalent structure in fungi) during mitotic interphase. In contrast, during meiotic prophase, centromeres dissociate from the SPB and telomeres cluster to the SPB. Recent studies revealed that this repositioning of chromosomes is regulated by mating pheromone signaling. Some centromere... Cell Division journals http://www.medworm.com/rss/comments.php?id=660326 Wed, 06 Jun 2007 04:00:00 +0100 660326 http://www.medworm.com/index.php?rid=658084&cid=s_34057_170_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F2%2F1%2F15 DNA double strand breaks are efficiently repaired by homologous recombination. One of the last steps of this process is resolution of Holliday junctions that are formed at the sites of genetic exchange between homologous DNA. Although various resolvases with Holliday junctions processing activity have been identified in bacteriophages, bacteria and archaebacteria, eukaryotic resolvases have been elusive. Recent biochemical evidence has revealed that RAD51C and XRCC3, members of the RAD51-like protein family, are involved in Holliday junction resolution in mammalian cells. However, purified recombinant RAD51C and XRCC3 proteins have not shown any Holliday junction resolution activity. In addition, these proteins did not reveal the presence of a nuclease domain, which raises doubts about the... Cell Division journals http://www.medworm.com/rss/comments.php?id=658084 Mon, 04 Jun 2007 04:00:00 +0100 658084 http://www.medworm.com/index.php?rid=610434&cid=s_34057_170_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F2%2F1%2F13 The cyclin kinase inhibitor p27kip1 acts as a potent tumor supressor protein in a variety of human cancers. Its expression levels correlate closely with the overall prognosis of the affected patient and often predict the outcome to different treatment modalities. In contrast to other tumor suppressor proteins p27 expression levels in tumor cells are frequently regulated by ubiquitin dependent proteolysis. Re-expression of p27 in cancer cells therefore does not require gene therapy but can be achieved by interfering with the protein turnover machinery. In this review we will summarize experimental results which highlight the potential use of p27 as a target for oncological therapies. (Source: Cell Division) Cell Division journals http://www.medworm.com/rss/comments.php?id=610434 Wed, 09 May 2007 04:00:00 +0100 610434 http://www.medworm.com/index.php?rid=596677&cid=s_34057_170_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F2%2F1%2F12 Movement through the cell cycle is controlled by the temporally and spatially ordered activation of cyclin-dependent kinases paired with their respective cyclin binding partners. Cell cycle events occur in a stepwise fashion and are monitored by molecular surveillance systems to ensure that each cell cycle process is appropriately completed before subsequent events are initiated. Cells prevent entry into mitosis while DNA replication is ongoing, or if DNA is damaged, via checkpoint mechanisms that inhibit the activators and activate the inhibitors of mitosis, Cdc25 and Wee1, respectively. Once DNA replication has been faithfully completed, Cdc2/Cyclin B is swiftly activated for a timely transition from interphase into mitosis. This sharp transition is propagated through both positive and n... Cell Division journals http://www.medworm.com/rss/comments.php?id=596677 Fri, 04 May 2007 04:00:00 +0100 596677 http://www.medworm.com/index.php?rid=470407&cid=s_34057_170_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F2%2F1%2F11 Ubiquitin is a highly versatile post-translational modification that controls virtually all types of cellular events. Over the past ten years we have learned that diverse forms of ubiquitin modifications and of ubiquitin binding modules co-exist in the cell, giving rise to complex networks of protein:protein interactions. A central problem that continues to puzzle ubiquitinologists is how cells translate this myriad of stimuli into highly specific responses. This is a classical signalling problem. Here, we draw parallels with the phosphorylation signalling pathway and we discuss the expanding repertoire of ubiquitin signals, signal tranducers and signalling-regulated E3 enzymes. We examine recent advances in the field, including a new mechanism of regulation of E3 ligases that relies on ub... Cell Division journals http://www.medworm.com/rss/comments.php?id=470407 Tue, 13 Mar 2007 04:00:00 +0100 470407 http://www.medworm.com/index.php?rid=456473&cid=s_34057_170_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F2%2F1%2F10 The retinoblastoma (Rb) tumor suppressor gene product, pRb, has an established role in the implementation of cellular senescence, the state of irreversible G1 cell cycle arrest provoked by diverse oncogenic stresses. In murine cells, senescence cell cycle arrest can be reversed by subsequent inactivation of pRb, indicating that pRb is required not only for the onset of cellular senescence, but also for the maintenance of senescence program in murine cells. However, in human cells, once pRb is fully activated by p16INK4a, senescence cell cycle arrest becomes irreversible and is no longer revoked by subsequent inactivation of pRb, suggesting that p16INK4a/Rb-pathway activates an alternative mechanism to irreversibly block the cell cycle in human senescent cells. Here, we discuss the molecula... Cell Division journals http://www.medworm.com/rss/comments.php?id=456473 Wed, 07 Mar 2007 05:00:00 +0100 456473 http://www.medworm.com/index.php?rid=456474&cid=s_34057_170_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F2%2F1%2F9 Conclusions: Our results show that FBXW7 expression is a prognostic marker for patients with glioblastoma. We suggest that loss of FBXW7 plays an important role in glioma malignancy by allowing the accumulation of multiple oncoproteins and that interfering with Fbxw7 or its downstream targets would constitute a new therapeutic advance. (Source: Cell Division) Cell Division journals http://www.medworm.com/rss/comments.php?id=456474 Tue, 27 Feb 2007 05:00:00 +0100 456474 http://www.medworm.com/index.php?rid=456475&cid=s_34057_170_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F2%2F1%2F8 DNA replication must be tightly controlled to prevent initiation of a second round of replication until mitosis is complete. So far, components of the pre-replicative complex (Cdt1, Cdc6 and geminin) were considered key players in this regulation. In a new study, Machida and Dutta have shown that depletion of Emi1 caused cells to replicate their DNA more than once per cell cycle 1. This effect was dependent on the ability of Emi1 to inhibit the APC/C. In addition to its role in regulating entry into mitosis, oscillation of APC/C activity regulates pre-RC formation: high APC/C activity in late M/G1 allows pre-RC formation and low APC/C activity in S/G2 prevents pre-RC formation for a second time thereby preventing rereplication. Each redundant pathway to prevent rereplication is dependent o... Cell Division journals http://www.medworm.com/rss/comments.php?id=456475 Fri, 23 Feb 2007 05:00:00 +0100 456475 http://www.medworm.com/index.php?rid=415280&cid=s_34057_170_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F2%2F1%2F7 Conclusions: Degradation of cyclin E by the Fbw7 pathway can, thus, be conditionally regulated either by Fbw7 dimerization or by hyperphosphorylation of the T380 phospho-degron. Other substrates, which cannot accommodate an extra phosphate in their phospho-degrons, or which dont provide a negatively charged amino acid in the +4 position, may be absolutely dependent on Fbw7 dimerization for their turnover. Our results point to an additional level of regulation for substrate interaction and turnover by Fbw7. (Source: Cell Division) Cell Division journals http://www.medworm.com/rss/comments.php?id=415280 Tue, 13 Feb 2007 07:00:00 +0100 415280 http://www.medworm.com/index.php?rid=415282&cid=s_34057_170_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F2%2F1%2F6 Haematopoietic cell number is maintained by a delicate balance between cell proliferation, differentiation and death. Gene knockout studies in mice have revealed the complex roles of cyclins, CDKs, and CDK inhibitors in regulating cell proliferation and differentiation in the haematopoietic system. These studies point to families of cell cycle regulators which display both redundant and unique roles within a lineage and developmental-stage specific manner. Moreover, the promiscuity of these cell cycle regulators is critical for haemopoietic cell proliferation and differentiation. In this review, we discuss the current evidence from mouse models that the complexity and multifarious nature of the haematopoietic system is critical for its form and function. (Source: Cell Division) Cell Division journals http://www.medworm.com/rss/comments.php?id=415282 Mon, 12 Feb 2007 07:00:00 +0100 415282 http://www.medworm.com/index.php?rid=389242&cid=s_34057_170_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F2%2F1%2F4 Oocytes from higher chordates, including man and nearly all mammals, arrest at metaphase of the second meiotic division before fertilization. This arrest is due to an activity that has been termed Cytostatic Factor. Cytostatic Factor maintains arrest through preventing loss in Maturation-Promoting Factor (MPF; CDK1/cyclin B). Physiologically, Cytostatic Factor -induced metaphase arrest is only broken by a calcium rise initiated by the fertilizing sperm and results in degradation of cyclin B, the regulatory subunit of MPF through the Anaphase-Promoting Complex/Cyclosome (APC/C). Arrest at metaphase II may therefore be viewed as being maintained by inhibition of the APC/C, and Cytostatic Factor as being one or more pathways, one of which inhibits the APC/C, consorting in the preservation of ... Cell Division journals http://www.medworm.com/rss/comments.php?id=389242 Fri, 26 Jan 2007 07:00:00 +0100 389242 http://www.medworm.com/index.php?rid=379676&cid=s_34057_170_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F2%2F1%2F3 Natura non facit saltum (nature makes no leap) the Latins used to say, meaning that nature does not like discontinuities. Cells make no exception and indeed any discontinuity in the DNA double helix is promptly detected, triggering an alteration of cell proliferation and an attempt to repair. Yet, linear chromosomes bear DNA ends that are compatible with normal cell proliferation and they escape, under normal conditions, any repair. How telomeres, the chromosomes tips, achieve that is not fully understood. We recently observed that the Rad9/Hus1/Rad1 (911) complex, previously known for its functions in DNA metabolism and DNA damage responses, is constitutively associated with telomeres and plays an important role in their maintenance. Here, we summarize the available data and discuss the p... Cell Division journals http://www.medworm.com/rss/comments.php?id=379676 Wed, 17 Jan 2007 07:00:00 +0100 379676 http://www.medworm.com/index.php?rid=379677&cid=s_34057_170_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F2%2F1%2F2 Cyclin D1 is an allosteric regulator for cyclin-dependent kinases 4 and 6 (CDK4/6). The cyclin D/CDK4 kinase promotes G1/S transition through the posttranslational modification and the subsequent inactivation of the retinoblastoma (Rb) protein and related family members (p107 and p130). Accumulation of cyclin D1 is tightly regulated through various mechanisms including transcription, protein localization and ubiquitin-dependent proteolysis. While regulators of cyclin D1 gene expression have been under considerable scrutiny, the identity of the protein complex that targets cyclin D1 protein for degradation, the putative E3 ubiquitin ligase, has remained obscure. In a recent report, Lin et al [1] describe the identification and characterization of a novel SCF, wherein FBX4 and alphaB-crystal... Cell Division journals http://www.medworm.com/rss/comments.php?id=379677 Mon, 15 Jan 2007 07:00:00 +0100 379677 http://www.medworm.com/index.php?rid=379678&cid=s_34057_170_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F2%2F1%2F1 Raf Kinase Inhibitory Protein (RKIP) is an evolutionarily conserved protein that functions as a modulator of signaling by the MAP kinase cascade. Implicated as a metastasis suppressor, Raf Kinase Inhibitory Protein depletion correlates with poor prognotsis for breast, prostate and melanoma tumors but the mechanism is unknown. Recent evidence indicates that Raf Kinase Inhibitory Protein regulates the mitotic spindle assembly checkpoint by controlling Aurora B Kinase activity, and the mechanism involves Raf/MEK/ERK signaling. In contrast to elevated MAP kinase signaling during the G1, S or G2 phases of the cell cycle that activates checkpoints and induces arrest or senescence, loss of RKIP during M phase leads to bypass of the spindle assembly checkpoint and the generation of chromosomal abn... Cell Division journals http://www.medworm.com/rss/comments.php?id=379678 Wed, 10 Jan 2007 07:00:00 +0100 379678 http://www.medworm.com/index.php?rid=379679&cid=s_34057_170_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F1%2F1%2F32 We present evidence that variations in cyclin D1 levels through the cell cycle are essential for continuing proliferation. Cyclin D1 levels must be high during G1 phase for a cell to initiate DNA synthesis, but then must be suppressed to low levels during S phase to allow for efficient DNA synthesis. This suppression during S phase is apparently regulated by cell cycle position alone and occurs automatically during each cell cycle. If the cell is to continue proliferating, cyclin D1 levels must be induced once again during G2 phase. This induction depends upon the activity of proliferative signaling molecules, and ensures that the extracellular environment continues to be conducive for growth. We propose that the suppression of cyclin D1 levels during each S phase ensures that the subseque... Cell Division journals http://www.medworm.com/rss/comments.php?id=379679 Mon, 18 Dec 2006 07:00:00 +0100 379679 http://www.medworm.com/index.php?rid=379680&cid=s_34057_170_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F1%2F1%2F29 Stem cells have recently attracted significant attention largely due to their potential therapeutic properties, but also because of their role in tumorigenesis and their resemblance, in many aspects, to cancerous cells. Understanding how stem cells are regulated, namely with respect to the control of their proliferation and differentiation within a functional organism, is thus primordial to safely profit from their therapeutic benefits. Here, we review recent advances in the understanding of germline stem cell proliferation control by factors that respond to the nutritional status and/or insulin signaling, through studies performed in C. elegans and Drosophila. Together, these data uncover some shared fundamental features that underlie the central control of cellular proliferation within a... Cell Division journals http://www.medworm.com/rss/comments.php?id=379680 Wed, 06 Dec 2006 07:00:00 +0100 379680 http://www.medworm.com/index.php?rid=379681&cid=s_34057_170_f&fid=34057&url=http%3A%2F%2Fwww.celldiv.com%2Fcontent%2F1%2F1%2F27 Abp1, and the closely related Cbh1 and Cbh2 are homologous to the human centromere-binding protein CENP-B that has been implicated in the assembly of centromeric heterochromatin. Fission yeast cells lacking Abp1 show an increase in mini-chromosome instability suggesting that Abp1 is important for chromosome segregation and/or DNA synthesis. Here we show that Abp1 interacts with the DNA replication protein Cdc23 (MCM10) in a two-hybrid assay, and that the Δabp1 mutant displays a synthetic phenotype with a cdc23 temperature-sensitive mutant. Moreover, genetic interactions were also observed between abp1+ and four additional DNA replication initiation genes cdc18+, cdc21+, orc1+, and orc2+. Interestingly, we find that S phase is delayed in cells deleted for abp1+ when released from a G1 bloc... Cell Division journals http://www.medworm.com/rss/comments.php?id=379681 Fri, 17 Nov 2006 07:00:00 +0100 379681