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Proteomics, Pathway Array and Signaling Network-Based Medicine in CancerEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 t...
Source: Cell Division - October 28, 2009 Category: Cytology Authors: David ZhangFei YeLing GaoXiaoliang LiuXin ZhaoYufang CheHongxia WangLibo WangJosephine WuDong SongWei LiuHong XuBo JiangWeijia ZhangJinhua WangPeng Lee Source Type: journals

P-TEFb- the final frontierEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Cell Division - September 1, 2009 Category: Cytology Authors: Jiri Kohoutek Source Type: journals

Septins: molecular partitioning and the generation of cellular asymmetryEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Cell Division - August 25, 2009 Category: Cytology Authors: Michael McMurrayJeremy Thorner Source Type: journals

RBX1/ROC1-SCF E3 ubiquitin ligase is required for mouse embryogenesis and cancer cell survivalEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Cell Division - August 5, 2009 Category: Cytology Authors: Lijun JiaYi Sun Source Type: journals

Smurf2 as a novel mitotic regulator: From the spindle assembly checkpoint to tumorigenesisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 c...
Source: Cell Division - July 6, 2009 Category: Cytology Authors: Evan OsmundsonDipankar RayFinola MooreHiroaki Kiyokawa Source Type: journals

Regulation of DNA replication by the S-Phase DNA damage checkpointEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 t...
Source: Cell Division - July 2, 2009 Category: Cytology Authors: Nicholas WillisNicholas Rhind Source Type: journals

Morphogenesis signaling components influence cell cycle regulation by cyclin dependent kinaseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Cell Division - June 30, 2009 Category: Cytology Authors: Brian TobeAna KitazonoJacqueline Suen GarciaRenee GerberBrooke BevisJohn ChoyDaniel ChasmanStephen Kron Source Type: journals

Akt finds its new path to regulate cell cycle through modulating Skp2 activity and its destruction by APC/Cdh1Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 strengthe...
Source: Cell Division - June 22, 2009 Category: Cytology Authors: Daming GaoHiroyuki InuzukaAlan TsengWenyi Wei Source Type: journals

CIP/KIP cyclin-dependent protein kinase inhibitors and the road to polyploidyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 endoredu...
Source: Cell Division - June 2, 2009 Category: Cytology Authors: Zakir UllahChrissie LeeMelvin DePamphilis Source Type: journals

A dual role of Cdk2 in DNA damage responseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 th...
Source: Cell Division - May 18, 2009 Category: Cytology Authors: Ande Satyanarayana and Philipp Kaldis Source Type: journals

New insights into the functions and regulation of the transcriptional corepressors SMRT and N-CoREmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Cell Division - April 21, 2009 Category: Cytology Authors: Kristopher J Stanya and Hung-Ying Kao Source Type: journals

Chemopreventive and renal protective effects for docosahexaenoic acid (DHA): implications of CRP and lipid peroxidesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Cell Division - April 2, 2009 Category: Cytology Authors: M E Elmesery, M M Algayyar, H A Salem, M M Darweish and A M El-Mowafy Source Type: journals

A microfluidic device to acquire high-magnification microphotographs of yeast cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Cell Division - March 24, 2009 Category: Cytology Authors: Shinsuke Ohnuki, Satrou Nogami and Yoshikazu Ohya Source Type: journals

Impact of steroid hormone signals on Drosophila cell cycle during developmentEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Cell Division - January 20, 2009 Category: Cytology Authors: Nicola Cranna and Leonie Quinn Source Type: journals

The emerging regulatory potential of SCFMet30 -mediated polyubiquitination and proteolysis of the Met4 transcriptional activatorEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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, ...
Source: Cell Division - July 25, 2008 Category: Cytology Authors: Srikripa Chandrasekaran and Dorota Skowyra Source Type: journals

The many faces of ubiquitinated histone H2A: insights from the DUBsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Cell Division - April 22, 2008 Category: Cytology Authors: Joseph H A Vissers, Francesco Nicassio, Maarten van Lohuizen, Pier Paolo Di Fiore and Elisabetta Citterio Source Type: journals

Cullin-RING ubiquitin ligases: global regulation and activation cyclesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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-recognitio...
Source: Cell Division - February 18, 2008 Category: Cytology Authors: Dimple R Bosu and Edward T Kipreos Source Type: journals

Genetic analysis of the spindle checkpoint genes san-1, mdf-2, bub-3 and the CENP-F like homologues hcp-1 and hcp-2 in Caenorhabditis elegansEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Cell Division - February 4, 2008 Category: Cytology Authors: Vinita A Hajeri, Anil M Stewart, Landon L Moore and Pamela A Padilla Source Type: journals

Emerging Roles of the SUMO Pathway in MitosisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Cell Division - January 24, 2008 Category: Cytology Authors: Mary Dasso Source Type: journals

Self-regulated mechanism of Plk1 localization to kinetochores : lessons from the Plk1-PBIP1 interactionEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 l...
Source: Cell Division - January 23, 2008 Category: Cytology Authors: Kyung S Lee, Doo-Yi Oh, Young H Kang and Jung-Eun Park Source Type: journals

Preventing DNA over-replication: a Cdk perspectiveEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 le...
Source: Cell Division - January 22, 2008 Category: Cytology Authors: Andrew CG Porter Source Type: journals

Human 14-3-3 gamma protein results in abnormal cell proliferation in the developing eye of Drosophila melanogasterEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Cell Division - January 14, 2008 Category: Cytology Authors: Sophia W Hong, Wenqing Qi, Marc Brabant, Giovanni Bosco and Jesse D Martinez Source Type: journals

Obituary: Arun FotedarEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
- (Source: Cell Division)
Source: Cell Division - October 2, 2007 Category: Cytology Authors: Rati Fotedar and Robert L Margolis Source Type: journals

Review of "The Cell Cycle: Principles of Control" by David O. MorganEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: Cell Division)
Source: Cell Division - September 17, 2007 Category: Cytology Authors: Mignon A Keaton Source Type: journals

Structure-function analysis of the retinoblastoma tumor suppressor protein - is the whole a sum of its parts?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This article will also discuss the prospects for using this approach to further explore the unknown functions of pRB. (Source: Cell Division)
Source: Cell Division - September 13, 2007 Category: Cytology Authors: Frederick A Dick Source Type: journals

Fez1/Lzts1 a new mitotic regulator implicated in cancer developmentEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ce...
Source: Cell Division - August 24, 2007 Category: Cytology Authors: Andrea Vecchione, Carlo M Croce and Gustavo Baldassarre Source Type: journals

Running on a treadmill: dynamic inhibition of APC/C by the spindle checkpointEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 mo...
Source: Cell Division - July 24, 2007 Category: Cytology Authors: Laura A Diaz-Martinez and Hongtao Yu Source Type: journals

The anti-apoptotic factor Che-1/AATF links transcriptional regulation, cell cycle control, and DNA damage responseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ph...
Source: Cell Division - July 16, 2007 Category: Cytology Authors: Claudio Passananti and Maurizio Fanciulli Source Type: journals

Cdt1 degradation to prevent DNA re-replication: conserved and non-conserved pathwaysEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 degrad...
Source: Cell Division - June 12, 2007 Category: Cytology Authors: Youngjo Kim and Edward T Kipreos Source Type: journals

Reconstruction of the kinetochore: a prelude to meiosisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Cell Division - June 6, 2007 Category: Cytology Authors: Haruhiko Asakawa, Tokuko Haraguchi and Yasushi Hiraoka Source Type: journals

Resolving RAD51C function in late stages of homologous recombinationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 prot...
Source: Cell Division - June 4, 2007 Category: Cytology Authors: Shyam K. Sharan and Sergey Kuznetsov Source Type: journals

p27kip1: a target for tumor therapies?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 th...
Source: Cell Division - May 9, 2007 Category: Cytology Authors: Irina Nickeleit, Steffen Zender, Uta Kossatz and Nisar P Malek Source Type: journals

Cdc25 and Wee1: analogous opposites?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 fait...
Source: Cell Division - May 4, 2007 Category: Cytology Authors: Jennifer A Perry and Sally Kornbluth Source Type: journals

The Ubiquitination code: a signalling problemEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 signal...
Source: Cell Division - March 13, 2007 Category: Cytology Authors: Tanja Woelk, Sara Sigismund, Lorenza Penengo and Simona Polo Source Type: journals

Irreversibility of cellular senescence: dual roles of p16INK4a/Rb-pathway in cell cycle controlEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 o...
Source: Cell Division - March 7, 2007 Category: Cytology Authors: Akiko Takahashi, Naoko Ohtani and Eiji Hara Source Type: journals

FBXW7/hCDC4 controls glioma cell proliferation in vitroand is a prognostic marker for survival in glioblastoma patientsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Cell Division - February 27, 2007 Category: Cytology Authors: Martin Hagedorn, Maylis Delugin, Isabelle Abraldes, Nathalie Allain, Marc-Antoine Belaud-Rotureau, Michelle Turmo, Claude Prigent, Hugues Loiseau, Andreas Bikfalvi and Sophie Javerzat Source Type: journals

APC/C – the master controller of origin licensing?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 a...
Source: Cell Division - February 23, 2007 Category: Cytology Authors: Umasundari Sivaprasad, Yuichi J Machida and Anindya Dutta Source Type: journals

Fbw7/hCDC4 dimerization regulates its substrate interactionsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Cell Division - February 13, 2007 Category: Cytology Authors: Markus Welcker and Bruce E Clurman Source Type: journals

Promiscuous and lineage-specific roles of cell cycle regulators in haematopoiesisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 evid...
Source: Cell Division - February 12, 2007 Category: Cytology Authors: Stephen S Myatt and Eric W-F Lam Source Type: journals

How eggs arrest at metaphase II: MPF stabilisation plus APC/C inhibition equals Cytostatic FactorEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 viewe...
Source: Cell Division - January 26, 2007 Category: Cytology Authors: Suzanne Madgwick and Keith T Jones Source Type: journals

Need telomere maintenance? Call 911Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 D...
Source: Cell Division - January 17, 2007 Category: Cytology Authors: Sofia Francia, Robert Weiss and Fabrizio dAdda di Fagagna Source Type: journals

SCF Fbx4/alphaB-crystallin cyclin D1 ubiquitin ligase: a license to destroyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Cell Division - January 15, 2007 Category: Cytology Authors: Olena Barbash, Douglas I Lin and J Alan Diehl Source Type: journals

MAP kinase meets mitosis: A role for Raf Kinase Inhibitory Protein in spindle checkpoint regulationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ac...
Source: Cell Division - January 10, 2007 Category: Cytology Authors: Marsha R Rosner Source Type: journals

Variations in cyclin D1 levels through the cell cycle determine the proliferative fate of a cellEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Cell Division - December 18, 2006 Category: Cytology Authors: Ke Yang, Masahiro Hitomi and Dennis W Stacey Source Type: journals

Regulation of germline stem cell proliferation downstream of nutrient sensingEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Cell Division - December 6, 2006 Category: Cytology Authors: Patrick Narbonne and Richard Roy Source Type: journals

The CENP-B homolog, Abp1, interacts with the initiation protein Cdc23 (MCM10) and is required for efficient DNA replication in fission yeastEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Cell Division - November 17, 2006 Category: Cytology Authors: Alexandra M Locovei, Maria-Grazia Spiga, Katsunori Tanaka, Yota Murakami and Gennaro D'Urso Source Type: journals