共查询到20条相似文献,搜索用时 15 毫秒
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Mitf cooperates with Rb1 and activates p21Cip1 expression to regulate cell cycle progression 总被引:1,自引:0,他引:1
Carreira S Goodall J Aksan I La Rocca SA Galibert MD Denat L Larue L Goding CR 《Nature》2005,433(7027):764-769
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Joo HY Zhai L Yang C Nie S Erdjument-Bromage H Tempst P Chang C Wang H 《Nature》2007,449(7165):1068-1072
Post-translational histone modifications have important regulatory roles in chromatin structure and function. One example of such modifications is histone ubiquitination, which occurs predominately on histone H2A and H2B. Although the recent identification of the ubiquitin ligase for histone H2A has revealed important roles for H2A ubiquitination in Hox gene silencing as well as in X-chromosome inactivation, the enzyme(s) involved in H2A deubiquitination and the function of H2A deubiquitination are not known. Here we report the identification and functional characterization of the major deubiquitinase for histone H2A, Ubp-M (also called USP16). Ubp-M prefers nucleosomal substrates in vitro, and specifically deubiquitinates histone H2A but not H2B in vitro and in vivo. Notably, knockdown of Ubp-M in HeLa cells results in slow cell growth rates owing to defects in the mitotic phase of the cell cycle. Further studies reveal that H2A deubiquitination by Ubp-M is a prerequisite for subsequent phosphorylation of Ser 10 of H3 and chromosome segregation when cells enter mitosis. Furthermore, we demonstrate that Ubp-M regulates Hox gene expression through H2A deubiquitination and that blocking the function of Ubp-M results in defective posterior development in Xenopus laevis. This study identifies the major deubiquitinase for histone H2A and demonstrates that H2A deubiquitination is critically involved in cell cycle progression and gene expression. 相似文献
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Bettencourt-Dias M Giet R Sinka R Mazumdar A Lock WG Balloux F Zafiropoulos PJ Yamaguchi S Winter S Carthew RW Cooper M Jones D Frenz L Glover DM 《Nature》2004,432(7020):980-987
Cycles of protein phosphorylation are fundamental in regulating the progression of the eukaryotic cell through its division cycle. Here we test the complement of Drosophila protein kinases (kinome) for cell cycle functions after gene silencing by RNA-mediated interference. We observed cell cycle dysfunction upon downregulation of 80 out of 228 protein kinases, including most kinases that are known to regulate the division cycle. We find new enzymes with cell cycle functions; some of these have family members already known to phosphorylate microtubules, actin or their associated proteins. Additionally, depletion of several signalling kinases leads to specific mitotic aberrations, suggesting novel roles for familiar enzymes. The survey reveals the inter-digitation of systems that monitor cellular physiology, cell size, cellular stress and signalling processes with the basic cell cycle regulatory machinery. 相似文献
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Molecular basis of control of mitotic cell division in eukaryotes 总被引:17,自引:0,他引:17
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Oocytes collected from prepubertal gilt ovaries were matured in vitro (IVM), and fertilized in vitro (IVF) or electrically activated. Phosphorylation of mitogenactivated protein kinase (MAPK) was detected with SDS-PAGE and
Western blotting, and translocation of ERK2 was observed with immunofluorescent cytochemistry. We found that the quantity of MAPK kept unchanged during oocyte maturation.
There was no phosphorylated MAPK in porcine oocytes at the germinal vesicle (GV) stage; a little MAPK was phosphorylated at
20 h of IVM; a high level phosphorylation was detected at 30 h, while MAPK phosphorylation decreased at 36 h; and then MAPK
phosphorylation increased again to the peak level from 40 to 60 h. ERK2 translocated from the peripheral cytoplasm to inner
cytoplasm and nuclear area during oocyte maturation. There was nearly no phosphorylated MAPK at 18 and 20 h of electrically
activated oocytes, but phosphorylation increased at 22 h. There was no phosphorylated MAPK at 12 h of IVF, while phosphorylation
resumed at 16 h. These results suggest that MAPK may play an important regulatory role in MI-MII transition, pronucleus formation
and the initiation of the first mitosis in pig eggs. 相似文献
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Novel cell cycle control of RNA synthesis in yeast 总被引:4,自引:0,他引:4
During the fission yeast cell cycle, the rate of polyadenylated messenger RNA synthesis doubles when the cell reaches a critical size. This size-related control maintains average mRNA content in balance with total cell mass during exponential growth, even in cells growing at different absolute growth rates per cell. 相似文献
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Control of eukaryotic cell proliferation involves an extended regulatory network, the complexity of which has made it difficult to understand the basic principles of the cell cycle. To investigate the core engine of the mitotic cycle we have generated a minimal control network in fission yeast that efficiently sustains cellular reproduction. Here we demonstrate that orderly progression through the major events of the cell cycle can be driven by oscillation of an engineered monomolecular cyclin-dependent protein kinase (CDK) module lacking much of the canonical regulation. We show further that the CDK oscillator acts as the primary organizer of the cell cycle, imposing timing and directionality to a system of two CDK activity thresholds that define independent cell cycle phases. We propose that this simple core architecture forms the basic control of the eukaryotic cell cycle. 相似文献
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Kai Shen YingJiang Ye KeWei Jiang Bin Liang XiaoDong Yang Shan Wang 《科学通报(英文版)》2012,57(20):2580-2585
We have investigated the role of MSH2,a mismatch repair gene in cell proliferation,cell cycle control and cell invasiveness in the SW480 human colorectal cancer cell line.RNAi-mediated inhibition of MSH2 expression was achieved using MSH2 shRNA lentiviral expression vectors.Effective knockdown of endogenous MSH2 expression was determined by real-time PCR analysis.The most efficient MSH2 knockdown vector was selected for subsequent studies using SW480 cells.Endogenous MSH2 mRNA levels decreased after lentiviral delivery of the MSH2-RNAi,indicating efficient silencing of MSH2 expression in SW480 cells.Cell proliferation,cell cycle progression and cell invasiveness were quantified by MTT assays,flow cytometry and transwell assays,respectively.RNAi-mediated inhibition of MSH2 expression in SW480 cells resulted in decreased cell proliferation,cell cycle arrest at the G0/G1 phase and decreased cell invasiveness.Taken together,these results provide evidence that MSH2 stimulates cell proliferation,promotes cell cycle progression and positively regulates cell invasiveness. 相似文献
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Release of specific protease during mitotic cycle of L5178Y murine leukaemic cells by sublethal autolysis 总被引:3,自引:0,他引:3
H B Bosmann 《Nature》1974,249(453):144-145
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细胞周期检测作为生物相容性评价指标的研究 总被引:9,自引:0,他引:9
应用体外细胞培养法,观察不同质量分数羟基磷灰石浸提液对L-929细胞的细胞学形态的影响,同时采用MTT比色法评价羟基磷灰石对L-929生长和增殖的影响,流式细胞仪检测羟基磷灰石浸提液对L-929 细胞生长周期及凋亡的影响.结果表明,羟基磷灰石浸提液对体外培养的细胞形态无明显影响,对细胞生长和增殖无明显抑制作用;不同质量分数材料浸提液的细胞毒性为0~1级;随羟基磷灰石浸提液质量分数的升高,细胞凋亡率逐渐上升;50%、75%、100%羟基磷灰石浸提液组能明显降低G0/G1期细胞比例,增加S,G2/M期细胞比例,能增加L-929细胞DNA的合成,促进细胞生长和组织修复.细胞周期检测是生物材料生物相容性评价的一种可靠方法和指标. 相似文献
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Björklund M Taipale M Varjosalo M Saharinen J Lahdenperä J Taipale J 《Nature》2006,439(7079):1009-1013
Many high-throughput loss-of-function analyses of the eukaryotic cell cycle have relied on the unicellular yeast species Saccharomyces cerevisiae and Schizosaccharomyces pombe. In multicellular organisms, however, additional control mechanisms regulate the cell cycle to specify the size of the organism and its constituent organs. To identify such genes, here we analysed the effect of the loss of function of 70% of Drosophila genes (including 90% of genes conserved in human) on cell-cycle progression of S2 cells using flow cytometry. To address redundancy, we also targeted genes involved in protein phosphorylation simultaneously with their homologues. We identify genes that control cell size, cytokinesis, cell death and/or apoptosis, and the G1 and G2/M phases of the cell cycle. Classification of the genes into pathways by unsupervised hierarchical clustering on the basis of these phenotypes shows that, in addition to classical regulatory mechanisms such as Myc/Max, Cyclin/Cdk and E2F, cell-cycle progression in S2 cells is controlled by vesicular and nuclear transport proteins, COP9 signalosome activity and four extracellular-signal-regulated pathways (Wnt, p38betaMAPK, FRAP/TOR and JAK/STAT). In addition, by simultaneously analysing several phenotypes, we identify a translational regulator, eIF-3p66, that specifically affects the Cyclin/Cdk pathway activity. 相似文献
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Pulverer B 《Nature》2001,413(6856):553
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Activation at M-phase of a protein kinase encoded by a starfish homologue of the cell cycle control gene cdc2+ 总被引:44,自引:0,他引:44
In both starfish and amphibian oocytes, the activity of a major protein kinase which is independent of Ca2+ and cyclic nucleotides increases dramatically at meiotic and mitotic nuclear divisions. The in vivo substrates of this kinase are unknown, but phosphorylation of H1 histone can be used as an in vitro assay. We have purified this kinase from starfish oocytes. The major band in the most highly purified preparation contained a polypeptide of relative molecular mass (Mr) 34,000 (34K). This is the same size as the protein kinase encoded by cdc2+, which regulates entry into mitosis in fission yeast and is a component of MPF purified from Xenopus. Here, we show that antibodies against p34 recognize the starfish 34K protein and propose that entry into meiotic and mitotic nuclear divisions involves activation of the protein kinase encoded by a homologue of cdc2+. Given the wide occurrence of cdc2+ homologues from budding yeast to Xenopus and human cells, this activation may act as a common mechanism controlling entry into mitosis in eukaryotic cells. 相似文献
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How bacteria regulate cell cycle progression at a molecular level is a fundamental but poorly understood problem. In Caulobacter crescentus, two-component signal transduction proteins are crucial for cell cycle regulation, but the connectivity of regulators involved has remained elusive and key factors are unidentified. Here we identify ChpT, an essential histidine phosphotransferase that controls the activity of CtrA, the master cell cycle regulator. We show that the essential histidine kinase CckA initiates two phosphorelays, each requiring ChpT, which lead to the phosphorylation and stabilization of CtrA. Downregulation of CckA activity therefore results in the dephosphorylation and degradation of CtrA, which in turn allow the initiation of DNA replication. Furthermore, we show that CtrA triggers its own destruction by promoting cell division and inducing synthesis of the essential regulator DivK, which feeds back to downregulate CckA immediately before S phase. Our results define a single integrated circuit whose components and connectivity can account for the cell cycle oscillations of CtrA in Caulobacter. 相似文献