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414 records returned

The Polyhomeotic protein induces hyperplastic tissue overgrowth through the activation of the JAK/STAT pathway.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Epigenetic mechanisms controlling cellular proliferation are essential to animal development. Moreover, altered levels of expression of the epigenetic regulator proteins are associated with the development and progression of human diseases like cancer. We have studied the effects of high levels of Polyhomeotic (PH) protein, a member of the Polycomb Group (PcG), during the proliferation of the imaginal discs in Drosophila. Overexpression of PH protein causes induction of proliferation, accompanied with induction of JNK-dependent apoptosis. As a result, massive hyperplastic overgrowth is produced and the corresponding di...
Source: Cell Cycle - November 20, 2009 Category: Cytology Authors: González I, Simón R, Busturia A Tags: Cell Cycle Source Type: journals

Genetic ablation of caveolin-1 increases neural stem cell proliferation in the subventricular zone (SVZ) of the adult mouse brain.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, dual-label immunofluorescence analysis of the proliferation marker, Ki67, and the stem cell markers, nestin and Sox2, was performed on brains of 8 week-old wild-type (WT) and Cav-1 knockout (KO) mice. Our results demonstrate an increased number of Ki67-positive nuclei in the subventricular zone (SVZ) of Cav-1 KO brains. Importantly, our dual-label immunofluorescence analyses demonstrate increased co-localization of Ki67 with both nestin and Sox2 in the SVZ of Cav-1 KO brains. Remarkably similar results were also obtained with Cav-2 and Cav-3 KO mouse brains as well, with increased proliferation of adult neur...
Source: Cell Cycle - November 20, 2009 Category: Cytology Authors: Jasmin JF, Yang M, Iacovitti L, Lisanti MP Tags: Cell Cycle Source Type: journals

Drugging the heat shock factor 1 pathway: Exploitation of the critical cancer cell dependence on the guardian of the proteome.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19901525 [PubMed - as supplied by publisher] (Source: Cell Cycle)
Source: Cell Cycle - November 13, 2009 Category: Cytology Authors: de Billy E, Powers MV, Smith JR, Workman P Tags: Cell Cycle Source Type: journals

Disruption of the PP1/GADD34 complex induces calreticulin exposure.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In response to some chemotherapeutic agents, tumor cells can translocate calreticulin (CRT), which is usually contained in the lumen of the endoplasmic reticulum, to the surface of the plasma membrane. This effect requires the phosphorylation of the eukaryotic initiation factor 2alpha(eIF2alpha) by the eIF2alpha kinase PERK, yet may also be triggered by inhibition of the eIF2alpha phosphatase, which is composed by a catalytic subunit (PP1) and a regulatory subunit (GADD34). Here, we addressed the question whether the dissociation of the PP1/GADD34 complex would be sufficient to trigger CRT exposure. Molecular modeling ...
Source: Cell Cycle - November 13, 2009 Category: Cytology Authors: Kepp O, Galluzzi L, Giordanetto F, Tesniere A, Vitale I, Martins I, Schlemmer F, Adjemian S, Zitvogel L, Kroemer G Tags: Cell Cycle Source Type: journals

Anti-malaria drug blocks proteotoxic stress response: Anti-cancer implications.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The number of physical conditions and chemical agents induce accumulation of misfolded proteins creating proteotoxic stress. This leads to activation of adaptive pro-survival pathway, known as heat shock response (HSR), resulting in expression of additional chaperones. Several cancer treatment approaches, such as proteasome inhibitor Bortezomib and hsp90 inhibitor geldanamycin, involve activation of proteotoxic stress. Low efficacy of these therapies is likely due to the protective effects of HSR induced in treated cells, making this pathway an attractive target for pharmacological suppression. We found that the anti-m...
Source: Cell Cycle - November 13, 2009 Category: Cytology Authors: Neznanov N, Gorbachev AV, Neznanova L, Komarov AP, Gurova KV, Gasparian AV, Banerjee AK, Almasan A, Fairchild RL, Gudkov AV Tags: Cell Cycle Source Type: journals

C. elegans mitotic cyclins have distinct as well as overlapping functions in chromosome segregation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Mitotic cyclins in association with the Cdk1 protein kinase regulate progression through mitosis in all eukaryotes. Here, we address to what extent mitotic cyclins in the nematode Caenorhabditis elegans provide overlapping functions or distinct biological activities. C. elegans expresses a single A-type cyclin (CYA-1), three typical B-type cyclins (CYB-1, CYB-2.1 and CYB-2.2), and one B3-subfamily member (CYB-3). While we observed clear redundancies between the cyb genes, cyb-1 and cyb-3 also contribute specific essential functions in meiosis and mitosis. CYB-1 and CYB-3 show similar temporal and spatial expression, bo...
Source: Cell Cycle - October 18, 2009 Category: Cytology Authors: van der Voet M, Lorson MA, Srinivasan DG, Bennett KL, van den Heuvel S Tags: Cell Cycle Source Type: journals

pRB/CKI pathways at the interface of cell cycle and development.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19823011 [PubMed - as supplied by publisher] (Source: Cell Cycle)
Source: Cell Cycle - October 14, 2009 Category: Cytology Authors: Ambros V Tags: Cell Cycle Source Type: journals

Bioelectric controls of cell proliferation: Ion channels, membrane voltage and the cell cycle.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
All cells possess long-term, steady-state voltage gradients across the plasma membrane. These transmembrane potentials arise from the combined activity of numerous ion channels, pumps and gap junction complexes. Increasing data from molecular physiology now reveal that the role of changes in membrane voltage controls, and is in turn controlled by, progression through the cell cycle. We review recent functional data on the regulation of mitosis by bioelectric signals, and the function of membrane voltage and specific potassium, sodium and chloride ion channels in the proliferation of embryonic, somatic and neoplastic ce...
Source: Cell Cycle - October 14, 2009 Category: Cytology Authors: Blackiston DJ, McLaughlin KA, Levin M Tags: Cell Cycle Source Type: journals

Targeting oncogenic signaling pathways by exploiting nanotechnology.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Two scientific areas have recently emerged that can revolutionize cancer chemotherapy. First, an understanding of the different cellular signaling pathways implicated in the development and progression of cancer resulting in poor prognosis and drug resistance, have identified potential drug targets. Inhibitors of signal transduction pathways are currently in the clinics. Secondly, nanotechnology has emerged as an exciting multidisciplinary field promising to provide breakthrough solutions to the problems of optimizing the efficacy or therapeutic index of anticancer agents. The promise of nanotechnology lies in the abil...
Source: Cell Cycle - October 14, 2009 Category: Cytology Authors: Basu S, Chaudhuri P, Sengupta S Tags: Cell Cycle Source Type: journals

The diverse roles of RNA helicases in RNAi.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
RNA interference (RNAi) is a regulatory gene silencing system found in nearly all eukaryotic organisms that employs small RNAs, typically 20-25 nucleotides long, to target complementary sequences found in mRNAs. RNA helicases use ATP to unwind double-stranded RNA (dsRNA), and are known to participate at nearly every level of RNA metabolism. A multitude of RNA helicases have been isolated from screens for essential RNAi factors, and even the earliest models of the RNAi pathway have presumed an RNA helicase to function at the level of small RNA duplex unwinding. However, while many components that function in RNAi have b...
Source: Cell Cycle - October 14, 2009 Category: Cytology Authors: Ambrus AM, Frolov MV Tags: Cell Cycle Source Type: journals

The Alox5 gene is a novel therapeutic target in cancer stem cells of chronic myeloid leukemia.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cancer stem cells (CSCs) are believed to be the initiating cells for many types of blood cancer and some solid tumors, and curative therapies of these cancers require eradicating CSCs. Specific targeting of CSCs but not normal stem cell counterparts is a correct strategy for developing new anti-cancer therapies, and the success of this approach relies on identification of specific target genes in CSCs. Using BCR-ABL-induced chronic myeloid leukemia (CML) as a cancer model, we recently identified arachidonate 5-lipoxygenase (5-LO) gene (Alox5) as a critical regulator for leukemia stem cells (LSCs) in CML. Without Alox5,...
Source: Cell Cycle - October 14, 2009 Category: Cytology Authors: Chen Y, Li D, Li S Tags: Cell Cycle Source Type: journals

3'UTR mediated regulation of the cyclin D1 proto-oncogene.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In mantle cell lymphoma (MCL), overexpression of cyclin D1 is the hallmark of malignant transformation and results from it's juxtaposition to the immunoglobulin heavy chain enhancer. In addition, genomic deletions or point mutations leading to premature truncation of the cyclin D1 3' untranslated region (UTR) have been reported in a several MCL patients as well as in cell lines isolated from various tumors types. We demonstrate that the expression of cyclin D1 with or without the 3'UTR has different phenotypic consequences in stably transduced fibroblasts, with the hyper-proliferative phenotype of cyclin D1 closely lin...
Source: Cell Cycle - October 14, 2009 Category: Cytology Authors: Deshpande A, Pastore A, Deshpande AJ, Zimmermann Y, Hutter G, Weinkauf M, Buske C, Hiddemann W, Dreyling M Tags: Cell Cycle Source Type: journals

Regulation of blood-testis barrier dynamics by focal adhesion kinase (FAK): An unexpected turn of events.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The blood-testis barrier (BTB) is conferred by co-existing tight junctions (TJs), basal ectoplasmic specializations (basal ES), desmosome-like junctions and gap junctions (GJs) between adjacent Sertoli cells near the basement membrane in the seminiferous epithelium. while the concept of the BTB has been known for more than a century and its significance to spermatogenesis discerned for more than five decades, its regulation has remained largely unknown. Recent studies, however, have demonstrated that focal adhesion kinase (FAK), a modulator of the integrin-based signaling that plays a crucial role in cell movement, apo...
Source: Cell Cycle - October 14, 2009 Category: Cytology Authors: Cheng CY, Mruk DD Tags: Cell Cycle Source Type: journals

Cell type-specific regulation of a replication origin residing within an AT-rich/LINE-1-rich isochore.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19823034 [PubMed - as supplied by publisher] (Source: Cell Cycle)
Source: Cell Cycle - October 14, 2009 Category: Cytology Authors: Kholodii G, Dantsevich O, Korobov G, Tarantul V Tags: Cell Cycle Source Type: journals

Cdh1 controls the stability of TACC3.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Transforming acidic coiled-coil protein 3 (TACC3) was reported to be important for regulating mitotic spindle assembly and chromosome segregation. While the protein level of TACC3 was shown to be altered during cell cycle progression, the molecular mechanism in controlling TACC3 level is unclear. Here, we show that TACC3 protein level can be regulated by Cdh1, a well known activator of anaphase-promoting complex/cyclosome. We identified Cdh1 as an interacting partner of TACC3 by a yeast array screen. Both in vitro and in vivo binding studies indicated that TACC3 can form complexes with Cdh1. Depletion of endogenous Cdh...
Source: Cell Cycle - October 14, 2009 Category: Cytology Authors: Jeng JC, Lin YM, Lin CH, Shih HM Tags: Cell Cycle Source Type: journals

MicroRNA responses and stress granule formation modulate the DNA damage response.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
DNA damage induced by UV irradiation provokes profound changes in gene expression. Both transcriptional regulation and posttranslational modification of proteins have been known for many years, but the involvement of microRNAs in regulation of mRNA translation has been described only recently. This level of gene expression regulation appears to operate at the intermediate time points between fast protein modifications (within minutes) and much slower transcriptional reprogramming (which takes several hours to days to develop). MicroRNAs most clearly contribute to regulation of cell cycle checkpoints and apoptosis, but ...
Source: Cell Cycle - October 14, 2009 Category: Cytology Authors: Pothof J, Verkaik NS, Hoeijmakers JH, van Gent DC Tags: Cell Cycle Source Type: journals

microRNAs regulate human embryonic stem cell division.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
microRNAs (miRNAs) regulate numerous physiological processes such as cell division and differentiation in many tissue types including stem cells. To probe the role that miRNAs play in regulating processes relevant to embryonic stem cell biology, we used RNA interference to silence DICER and DROSHA, the two main miRNA processing enzymes. Consistent with a role for miRNAs in maintaining normal stem cell division and renewal, we found that perturbation of miRNA pathway function in human embryonic stem cells (hESCs) attenuates cell proliferation. Normal cell growth can be partially restored by introduction of the mature mi...
Source: Cell Cycle - October 14, 2009 Category: Cytology Authors: Qi J, Yu JY, Shcherbata HR, Mathieu J, Wang AJ, Seal S, Zhou W, Stadler BM, Bourgin D, Wang L, Nelson A, Ware C, Raymond C, Lim LP, Magnus J, Ivanovska I, Diaz R, Ball A, Cleary MA, Ruohola-Baker H Tags: Cell Cycle Source Type: journals

Sch9 partially mediates TORC1 signaling to control ribosomal RNA synthesis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
TORC1 is a central regulator of ribosomal RNA synthesis. Here we report that Sch9 partially mediates TORC1 signaling to regulate Pol I- and Pol III-dependent transcription. Mechanistically, Sch9 is involved in hyperphosphorylation and cytoplasmic localization of Maf1, and for optimal synthesis of rRNAs and tRNAs. Interestingly, sch9Delta does not affect Maf1 basal phosphorylation and nucleolar localization. In addition, TORC1 is still capable of regulating rRNAs and tRNAs in the absence of Sch9. Moreover, the hyperactive Sch9(2D3E) mutant does not confer significant rapamycin resistance in cell growth. Together, these ...
Source: Cell Cycle - October 14, 2009 Category: Cytology Authors: Wei Y, Zheng XF Tags: Cell Cycle Source Type: journals

Chromosomal instability: A composite phenotype that influences sensitivity to chemotherapy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Chromosomal instability (CIN) is defined as continual gain or loss of whole chromosomes or fractions of chromosomes and is a major cause of the genomic instability that characterizes most solid tumors. CIN is associated with intrinsic resistance to taxanes, acquired multidrug resistance and poor prognosis in many solid tumors, although recent evidence has shown that platinum agents, such as carboplatin, may specifically target CIN cancers. The molecular basis for the increased genomic instability seen in CIN tumors and the mechanisms linking this instability to drug resistance are poorly understood, although some clues...
Source: Cell Cycle - October 8, 2009 Category: Cytology Authors: McClelland SE, Burrell RA, Swanton C Tags: Cell Cycle Source Type: journals

Enhancement of cancer chemotherapy by simultaneously altering cell cycle progression and DNA-damage defenses through global modification of the serine/threonine phospho-proteome.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Despite improvements in the therapeutic efficacy of rationally designed cancer treatment regimens, most cancers remain incurable once spread beyond their sites of origin. Failure to achieve sustained control or eradication of cancers arises in large part because a subpopulation of quiescent "cancer stem cells" is insensitive to drugs targeting cell growth and replication and because defense mechanisms critical to survival of the normal cell also protect the cancer cell from cytotoxic injury. Global alteration of signal transduction by inhibition of serine/threonine dephosphorylation has recently been shown to markedly ...
Source: Cell Cycle - October 8, 2009 Category: Cytology Authors: Zhuang Z, Lu J, Lonser R, Kovach JS Tags: Cell Cycle Source Type: journals

The My(c)stery of iNKT cell ontogeny.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Invariant Valpha14 bearing natural killer T cells (iNKT) cells constitute a subset of lymphocytes that recognize lipid-based ligands presented by the non-classical MHC class I-like molecule CD1d and responds with rapid cytokine production. Despite their multiple implications in regulating immune responses, pertaining to cancer and auto-immunity, the molecular requirements for their development in the thymus are poorly understood. Here we discuss recent evidence that c-Myc mediates an intrathymic proliferation wave immediately following agonist selection of iNKT cells that is vital for the generation of mature iNKT cell...
Source: Cell Cycle - September 11, 2009 Category: Cytology Authors: Dose M, Gounari F Tags: Cell Cycle Source Type: journals

Temporal differences in DNA replication during the S phase using single fiber analysis of normal human fibroblasts and glioblastoma T98G cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We have recently shown that replication forks pause near origins in normal human fibroblasts (NHF1-hTERT) but not glioblastoma T98G cells. This observation led us to question whether other differences in the replication program may exist between these cell types that may relate to their genetic integrity. To identify differences, we detected immunoflourescently the sequential incorporation of the nucleotide analogs IdU and CldU into replicating DNA at the start of every hour of a synchronized S phase. We then characterized the patterns of labeled replicating DNA tracks and quantified the percentages and lengths of the ...
Source: Cell Cycle - September 11, 2009 Category: Cytology Authors: Frum RA, Khondker ZS, Kaufman DG Tags: Cell Cycle Source Type: journals

The N-terminal domain of DDA3 regulates the spindle-association of the microtubule depolymerase Kif2a and controls the mitotic function of DDA3.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
DDA3 is a microtubule-associated protein that controls chromosome congression and segregation by regulating the dynamics of the mitotic spindle. Depletion of DDA3 alters spindle structure, generates unaligned chromosomes at metaphase, and delays the mitotic progression. DDA3 interacts with the microtubule depolymerase Kif2a and controls the association of Kif2a to the mitotic spindle and the dynamic turnover of microtubules in the spindle. To understand the function and regulation of DDA3, we analyzed its domain structure and found that the C-terminal domain of DDA3 directly binds to microtubules in vitro and associate...
Source: Cell Cycle - September 11, 2009 Category: Cytology Authors: Jang CY, Fang G Tags: Cell Cycle Source Type: journals

tRNA genes in eukaryotic genome organization and reorganization.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The primary function of tRNA genes is to provide the templates for the transcription of essential tRNA molecules. However, there is now evidence that these dispersed repetitive elements have the potential to mediate the spatial and functional organization of the genome and to drive genome change and evolution. Indeed, tRNA genes and related Pol III promoter elements can occupy distinct subnuclear positions and also provide barriers which functionally separate domains of chromatin. Furthermore, tRNA genes can also represent barriers to DNA replication fork progression and accordingly, tRNA genes can contribute to the fo...
Source: Cell Cycle - September 11, 2009 Category: Cytology Authors: McFarlane RJ, Whitehall SK Tags: Cell Cycle Source Type: journals

NFkappaB inhibitors: Strategies from poxviruses.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The orchestration of the inflammatory responses to both infection and tissue damage is arguably the key physiological function of NFkappaB, and thus interference with the activation of NFkappaB represents an exceptional strategy for a successful pathogen to exploit to counter multiple host innate defense processes through the targeting of a single host regulatory pathway. Because of their large genomes, which typically encode approximately 200 proteins, and their unusual independence from the host nuclear transcriptional machinery, poxviruses are especially well suited to manipulate the cytoplasmic activation of NFkapp...
Source: Cell Cycle - September 11, 2009 Category: Cytology Authors: Mohamed MR, McFadden G Tags: Cell Cycle Source Type: journals

The apoptosis modulating role of SAP (SLAM associated protein) contributes to the symptomatology of the X linked lymphoproliferative disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Deletion or mutation of the SH2D1A gene located at Xq25 is responsible for the development of the X-linked lymphoproliferative disease, XLP. Primary infection of the affected individuals with EBV leads to fulminant and often fatal infectious mononucleosis, FIM. Moreover, they run a 200 fold elevated risk for lymphoma development. Due to the critical role of the immune response for the outcome of EBV infection and the detection of EBV genomes in several malignancies, XLP studies have been mainly focused on the immunological aspects. The involvement of SAP in the apoptotic machinery provides a further aspect in the compl...
Source: Cell Cycle - September 11, 2009 Category: Cytology Authors: Nagy N, Matskova L, Hellman U, Klein G, Klein E Tags: Cell Cycle Source Type: journals

Mechanism of dominant-negative telomerase function.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Human telomerase uses its integral core components, hTR and hTERT, to maintain telomeres in many cell types. Expression of a dominant-negative mutant of the catalytic subunit of telomerase, DN-hTERT, has been shown to cause telomere shortening and ultimately cell death in a number of tumor-derived cell lines. However, the mechanism of dominant-negative hTERT function and its fate inside the cell are still unknown. In order to understand the effect of the dominant-negative on wild-type hTERT, each was fused with GFP and expressed in telomerase-positive cells. GFP-DN-hTERT expression resulted in cytoplasmic exportation a...
Source: Cell Cycle - September 11, 2009 Category: Cytology Authors: Nguyen BN, Elmore LW, Holt SE Tags: Cell Cycle Source Type: journals

Hypoxia-mediated regulation of Cdc25A phosphatase by p21 and miR-21.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Hypoxia is a common feature of solid tumors and represents a critical factor in their progression and responsiveness to chemotherapy and radiotherapy. We now report that hypoxic exposure of colon cancer cells decreased the protein levels of the cell cycle-controlling phosphatase Cdc25A. Hypoxia decreased the mitotic population and caused S-phase arrest in these cells. Suppression of Cdc25A was phosphatase family member-specific, as a similar decrease was not observed with closely related Cdc25B or Cdc25C phosphatases. Pharmacological and genetic blockade of Chk1 and Chk2 failed to inhibit the hypoxia-mediated loss of C...
Source: Cell Cycle - September 11, 2009 Category: Cytology Authors: Queiroz de Oliveira PE, Zhang L, Wang Z, Lazo JS Tags: Cell Cycle Source Type: journals

Induced pluripotent stem cells from swine (Sus scrofa): Why they may prove to be important.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Three recent papers, published almost simultaneously by different groups, have described the generation of induced pluripotent stem (iPS) cells from the pig, a species whose size, anatomy and physiology render them attractive as clinical models for the human. The approach used in each case was to infect somatic cells with integrating retroviral vectors designed to express four reprogramming genes (POU5F1, SOX2, cMYC and KLF4). The cell lines generated met the standard criteria for pluripotency, including the ability to differentiate along multiple tissue lineages. In most respects, the porcine iPS cells more resembled ...
Source: Cell Cycle - September 11, 2009 Category: Cytology Authors: Roberts RM, Telugu BP, Ezashi T Tags: Cell Cycle Source Type: journals

Cancer stem cells and escape from drug-induced premature senescence in human lung tumor cells: Implications for drug resistance and in vitro drug screening models.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, using an in vitro human tumor model, we show that non-small lung adenocarcinoma A549 cells after treatment with DNA damaging antitumor drugs become permanently growth-arrested as a result of so-called drug-induced premature senescence (pseudo-senescence). However, a small fraction of drug-treated cells escapes pseudo-senescence that leads to regrowth of tumor cell population after drug treatment. We show that this re-growth is associated with the presence of cancer stem cells (CSCs) in lung tumor cell population. We also document that re-growth of CSCs can be greatly delayed if lung tumor cells are treated w...
Source: Cell Cycle - September 11, 2009 Category: Cytology Authors: Sabisz M, Skladanowski A Tags: Cell Cycle Source Type: journals

Inflammation: A hidden path to breaking the spell of ovarian cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Epithelial ovarian cancer is a highly lethal gynecological cancer for which overall prognosis has remained poor over the past few decades. A number of theories have been postulated in an effort to explain the etiology of epithelial ovarian cancer, each of which has been both applauded and doubted. Of note, these theories likely are not mutually exclusive, as they all converge more or less on the role of inflammation in promoting ovarian tumorigenesis. In this review, we describe the latest studies on the role of inflammation in the initiation and progression of epithelian ovarian cancer from three major aspects: physio...
Source: Cell Cycle - September 11, 2009 Category: Cytology Authors: Shan W, Liu J Tags: Cell Cycle Source Type: journals

Somatic hypermutation: Processivity of the cytosine deaminase AID and error-free repair of the resulting uracils.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The somatic hypermutation (SHM) process is initiated in activated B lymphocytes by the cytosine DNA deaminase AID creating uracils that are further treated by DNA replication and/or error-prone base excision repair (BER) and/or error-prone mismatch repair (MMR), resulting in mutations at the targeted cytosines, as well as at all four nucleotides neighboring the AID-induced uracil. In this analysis we investigate two issues that are specific to SHM, the processivity of AID in vivo in vertebrate cells versus in cell free assays, and the error-prone versus error-free repair of the AID-induced uracils. Compilation of publi...
Source: Cell Cycle - September 11, 2009 Category: Cytology Authors: Storb U, Shen HM, Nicolae D Tags: Cell Cycle Source Type: journals

Spindle apparatus uncoupling in endo-tetraploid asymmetric division of stem and non-stem cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19738438 [PubMed - as supplied by publisher] (Source: Cell Cycle)
Source: Cell Cycle - September 11, 2009 Category: Cytology Authors: Walen KH Tags: Cell Cycle Source Type: journals

IRS-2, but not IRS-1, can sustain proliferation and rescue UBF stabilization in InR or InR defective signaling of 32D myeloid cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Despite both IRS-1 and IRS-2 are two important adaptor molecules essential for intracellular signaling of insulin and IGF-I, the distinct biological pattern of IRS-2 versus IRS-1 remains as a concernful issue to be clarified. We demonstrated here an important evidence that in 32D myeloid cells expressing the insulin receptor (InR) or selected mutants of the InR, IRS-2, but not IRS-1, is required for promoting the proliferation and inhibiting the granulocytic differentiation, thus restore ERKs phosphorylation and UBF1 stabilization. In addition, unlike IRS-1, IRS-2 can effectively compensate the InR defective signaling ...
Source: Cell Cycle - September 11, 2009 Category: Cytology Authors: Wu S, Zhou B, Xu L, Sun H Tags: Cell Cycle Source Type: journals

A new (and different) circadian pacemaker.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19729993 [PubMed - as supplied by publisher] (Source: Cell Cycle)
Source: Cell Cycle - September 5, 2009 Category: Cytology Authors: Mohawk JA, Menaker M Tags: Cell Cycle Source Type: journals

Dynamics of the recovery from sRNA-mediated gene silencing.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19729996 [PubMed - as supplied by publisher] (Source: Cell Cycle)
Source: Cell Cycle - September 5, 2009 Category: Cytology Authors: Semsey S, Benjamin JA, Mitarai N, Krishna S, Csiszovszki Z, Sneppen K, Massé E Tags: Cell Cycle Source Type: journals

Spermidinyl-CoA-based HAT inhibitors block DNA repair and provide cancer-specific chemo- and radiosensitization.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Acetyl group turnover on specific lysine epsilon-amino groups of the core chromosomal histones regulates DNA accessibility function, and the acetylating and deacetylating enzymes that govern the turnover provide important targets for the development of anti-cancer drugs. Histone deacetylase (HDAC) inhibitors have been developed and evaluated extensively in clinical trials, while the development of inhibitors of histone acetyltransferase (HAT) has proceeded more slowly. Here we have examined the cellular effects of an S-substituted coenzyme A (CoA) inhibitor of histone acetylation, consisting of spermidine (Spd) linked ...
Source: Cell Cycle - August 7, 2009 Category: Cytology Authors: Bandyopadhyay K, Banères JL, Martin A, Blonski C, Parello J, Gjerset RA Tags: Cell Cycle Source Type: journals

RAKing in AKT: A tumor suppressor function for the intracellular tyrosine kinase FRK.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The Fyn related kinase FRK, originally called RAK, is a member of a small family of intracellular Src-related tyrosine kinases that includes PTK6 and Srms. These kinases share a conserved gene structure that is distinct from that of the Src family. Expression of FRK and PTK6 was originally identified in melanoma, breast cancer cells and normal intestinal epithelium, and both FRK and PTK6 have been implicated in the regulation of epithelial cell differentiation and apoptosis. Recently FRK was reported to phosphorylate the tumor suppressor PTEN (phosphatase and tensin homolog deleted from chromosome 10), a negative regul...
Source: Cell Cycle - August 7, 2009 Category: Cytology Authors: Brauer PM, Tyner AL Tags: Cell Cycle Source Type: journals

PUMA cooperates with direct activator proteins to promote mitochondrial outer membrane permeabilization and apoptosis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The BCL-2 family of proteins regulates apoptosis by controlling mitochondrial outer membrane permeabilization (MOMP). Within the family there are numerous protein-protein interactions that influence MOMP; however, defining the ultimate signal that commits a cell to apoptosis remains controversial. We chose to examine the function of the BH3-only protein, p53 upregulated modulator of apoptosis (PUMA), to define its contribution to MOMP and cooperation with the direct activator proteins. PUMA is a potent regulator of MOMP and our data suggest that this function is attributed to two distinct mechanisms which both rely on ...
Source: Cell Cycle - August 7, 2009 Category: Cytology Authors: Chipuk JE, Green DR Tags: Cell Cycle Source Type: journals

Chromosome cohesion and the spindle checkpoint.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Accurate chromosome segregation constitutes the basis of inheritance. Mistakes in chromosome segregation during mitosis lead to aneuploidy, a common feature of tumors. The accuracy of chromosome segregation is governed by a complex network of processes which ensure that each daughter cell receives the correct number of chromosomes. Herein we review recent developments in the understanding of chromosome segregation, focusing on the cohesion that holds the sister chromatids together and the spindle checkpoint which regulates anaphase onset. PMID: 19652532 [PubMed - as supplied by publisher] (Source: Cell Cycle)
Source: Cell Cycle - August 7, 2009 Category: Cytology Authors: Díaz-Martínez LA, Clarke DJ Tags: Cell Cycle Source Type: journals

Wild-type p53 protects normal cells against apoptosis induced by thiostrepton.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we compared the sensitivity of normal BJ human fibroblasts, BJ fibroblasts with p53 knockdown and corresponding BJ immortal/oncogenic cell lines with inactivated p53 to anticancer drug-induced apoptosis. We found that only normal cells that have wild-type p53 were resistant to the thiazole antibiotic, thiostrepton, suggesting that p53 plays an antiapoptotic role in normal cells. In this case p53 status, but not the transformation of cells per se determines their sensitivity to thiostrepton and possibly to other anticancer drugs. Since p53 is mutated in 50% of human cancers, thiostrepton may selectively kill ...
Source: Cell Cycle - August 7, 2009 Category: Cytology Authors: Halasi M, Schraufnagel DP, Gartel AL Tags: Cell Cycle Source Type: journals

Cdk2 plays a critical role in hepatocyte cell cycle progression and survival in the setting of cyclin D1 expression in vivo.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, our studies demonstrate that cdk2 plays a role in liver regeneration. Furthermore, it is essential for centrosome overduplication, proliferation and survival of hepatocytes that aberrantly express cyclin D1 in vivo. These studies suggest that cdk2 may warrant further investigation as a target for therapy of liver tumors with constitutive cyclin D1 expression. PMID: 19652536 [PubMed - as supplied by publisher] (Source: Cell Cycle)
Source: Cell Cycle - August 7, 2009 Category: Cytology Authors: Hanse EA, Nelsen CJ, Goggin MM, Anttila CK, Mullany LK, Berthet C, Kaldis P, Crary GS, Kuriyama R, Albrecht JH Tags: Cell Cycle Source Type: journals

Inverse system perturbations as a new methodology for identifying transcriptomic signaling participants in balanced biological processes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We devise a novel, systems-biology approach for identifying genetic participants in homeostatic biological processes. The central idea is that genes which are inversely regulated in alignment with positive and negative system perturbation are strong candidates for significant regulatory involvement in a given homeostatic process. This allows us to integrate known genetic participants together with hitherto unknown ones into a signaling network. We illustrate this concept and justify the underlying rationale in the exemplary case of the formation of blood vessels (angiogenesis) in the progression of pancreatic cancer wh...
Source: Cell Cycle - August 7, 2009 Category: Cytology Authors: Hauser K, Abdollahi A, Huber PE Tags: Cell Cycle Source Type: journals

Common light signaling pathways controlling DNA repair and circadian clock entrainment in zebrafish.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we show that light directly activates MAPK signaling cascades in zebrafish cells and we provide evidence that light-induced activation of these pathways controls the expression of two evolutionary-related genes, z64Phr and zCry1a, revealing that light-dependent DNA repair and the entrainment of circadian clock share common regulatory pathways. PMID: 19652538 [PubMed - as supplied by publisher] (Source: Cell Cycle)
Source: Cell Cycle - August 7, 2009 Category: Cytology Authors: Hirayama J, Miyamura N, Uchida Y, Asaoka Y, Honda R, Sawanobori K, Todo T, Yamamoto T, Sassone-Corsi P, Nishina H Tags: Cell Cycle Source Type: journals

Whither the replisome: Emerging perspectives on the dynamic nature of the DNA replication machinery.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Replisomes were originally thought to be multi-protein machines with a stabile and defined structure during replication. Discovery that replisomes repeatedly discard sliding clamps and assemble a new clamp to start each Okazaki fragment provided the first hint that the replisome structure changes during replication. Recent studies reveal that the replisome is more dynamic than ever thought possible. Replisomes can utilize many different polymerases; the helicase is regulated to travel at widely different speeds; leading and lagging strands need not always act in a coupled fashion with DNA loops; and the replication for...
Source: Cell Cycle - August 7, 2009 Category: Cytology Authors: Langston LD, Indiani C, O'Donnell M Tags: Cell Cycle Source Type: journals

The Myc-nucleophosmin-ARF network: A complex web unveiled.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this report we demonstrate that in the presence of ARF, NPM overexpression dramatically inhibits c-Myc-induced p53-independent apoptosis, while enhancing proliferation and transformation. We find that NPM sequesters ARF in nucleoli, blocking the relocalization of ARF to the nucleoplasm caused by activation of c-Myc. Therefore, the fate of a cell to undergo apoptosis or become transformed is dependent on this complex interacting network of oncogenic and tumor suppressor proteins. PMID: 19652540 [PubMed - as supplied by publisher] (Source: Cell Cycle)
Source: Cell Cycle - August 7, 2009 Category: Cytology Authors: Li Z, Hann SR Tags: Cell Cycle Source Type: journals

PML: A tumor suppressor that regulates cell fate in mammary gland.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The tumor suppressor promyelocytic leukemia protein (PML) is possibly unique in that its tumor suppressive functions may be attributed to both the protein and the conspicuous nuclear bodies (PML-NBs) that PML builds. Untangling the role of either the protein or its domain in cell fate has been a decade long task which has just received new impetus from developmental biologists. PML appears to play a central role in regulating stem and progenitor cell fate in tissues as diverse as blood, brain and breast. Our studies have uncovered an inverse relationship between the activity of certain Stat transcription factors and PM...
Source: Cell Cycle - August 7, 2009 Category: Cytology Authors: Li W, Rich T, Watson CJ Tags: Cell Cycle Source Type: journals

A new role for hth in the early pre-blastodermic divisions in drosophila.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this report, we show that the Homothorax (Hth) transcription factor is maternally provided and that its function is necessary for the proper assembly of the centric/centromeric heterochromatin during preblastodermic divisions. Embryos lacking the hth maternally-derived transcript, show abnormal localisation of the centromeric CID protein, and aberrant chromosomal segregation. In this syncytial context, Hth presumably acts together with its partner Extradenticle (Exd) and the RNA PolII, to facilitate transcription of satellite repeats. The transcripts derived from these sequences are needed for the correct assembly of th...
Source: Cell Cycle - August 7, 2009 Category: Cytology Authors: Salvany L, Aldaz S, Corsetti E, Azpiazu N Tags: Cell Cycle Source Type: journals

Structure of the Fas/FADD complex: A conditional death domain complex mediating signaling by receptor clustering.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Death domain complexes are key protein arrangements in the regulation of various cellular signaling events. One of the most prominent death domain complexes first described in the initiation of apoptosis is formed by the transmembrane receptor Fas, the cytosolic adaptor protein FADD, and caspase-8 and is referred to as the Fas/FADD/caspase-8 death inducing signaling complex (DISC). The recent structure of the Fas/FADD death domain complex reveals how formation of this signaling platform can be stringently regulated utilizing only Fas receptor clustering to form a death domain network. This work reveals that an opening ...
Source: Cell Cycle - August 7, 2009 Category: Cytology Authors: Salvesen GS, Riedl SJ Tags: Cell Cycle Source Type: journals

Polo-like kinase 1 (Plk1) in non-melanoma skin cancers.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we determined the expression profile of Plk1 in non-melanoma skin cancers viz. basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Our data demonstrated that like melanoma, Plk1 is significantly overexpressed in BCC and SCC samples. Further, we also found that compared to normal human epidermal keratinocytes (NHEKs), Plk1 was overexpressed at both the protein and mRNA levels in squamous A253 and A431 cells. In addition, a similar protein expression pattern was found for the downstream targets of Plk1, viz. Cdk1, Cyclin B1 and Cdc25C. We believe that the expression pattern of Plk1 in the various ski...
Source: Cell Cycle - August 7, 2009 Category: Cytology Authors: Schmit TL, Zhong W, Nihal M, Ahmad N Tags: Cell Cycle Source Type: journals