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Mitosis persists in the absence of Cdk1 activity when proteolysis or protein phosphatase activity is suppressed

热1 阿平添加于 2009-1-15 18:14 | 2957 次阅读 | 0 个评论

作者
Skoufias DA, Indorato R-L, Lacroix F, Panopoulos A, Margolis RL
摘要
Cellular transition to anaphase and mitotic exit has been linked to the loss of cyclin-dependent kinase 1 (Cdk1) kinase activity as a result of anaphase-promoting complex/cyclosome (APC/C)-dependent specific degradation of its cyclin B1 subunit. Cdk1 inhibition by roscovitine is known to induce premature mitotic exit, whereas inhibition of the APC/C-dependent degradation of cyclin B1 by MG132 induces mitotic arrest. In this study, we find that combining both drugs causes prolonged mitotic arrest in the absence of Cdk1 activity. Different Cdk1 and proteasome inhibitors produce similar results, indicating that the effect is not drug specific. We verify mitotic status by the retention of mitosis-specific markers and Cdk1 phosphorylation substrates, although cells can undergo late mitotic furrowing while still in mitosis. Overall, we conclude that continuous Cdk1 activity is not essential to maintain the mitotic state and that phosphatase activity directed at Cdk1 substrates is largely quiescent during mitosis. Furthermore, the degradation of a protein other than cyclin B1 is essential to activate a phosphatase that, in turn, enables mitotic exit.
详细资料
- 关键词: 2-Aminopurine/analogs & derivatives/pharmacology; CDC2 Protein Kinase/*antagonists & inhibitors; Coloring Agents; Cysteine Proteinase Inhibitors/pharmacology; Drug Interactions; Enzyme Inhibitors/pharmacology; Fluorescein-5-isothiocyanate; Fluorescent Antibody Technique, Indirect; Fluorescent Dyes; HCT116 Cells; Hela Cells; Humans; Hydrolysis; Lactams/pharmacology; Leupeptins/pharmacology; Mitosis/*drug effects; Phosphoprotein Phosphatases/*antagonists & inhibitors; Propidium; Protei
- 文献种类: Journal Article
- 期刊名称: The Journal of Cell Biology
- 期卷页: 2007年第179卷第4期 671-685页
- 地址: Institut de Biologie Structurale Jean-Pierre Ebel, Atomic Energy Commission/Centre National de la Recherche Scientifique, 38027 Grenoble, Cedex 1, France. dimitrios.skoufias@ibs.fr
- ISBN: 1540-8140
学科领域生物医药 » 生物学
标签

有丝分裂磷酸化 PP1 PP2A APC MG132 roscovitine
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阿平的文献笔记订阅

结论： 1.用MG132可以将细胞阻滞在Mitosis。 2.用roscovitine可以使细胞提前走出Mitosis。 3.MG132+roscovitine细胞还是无法提前走出Mitosis 4.cdk1磷酸化底物在加roscovitine后在没有磷酸酶的帮助下无法去磷酸化似乎是需要蛋白酶的存在去裂解某个蛋白（不是cyclin B1和securin），然后激活磷酸蛋白酶（PP1/PP2A），使cdk1的磷酸化底物去磷酸化，而这些底物的去磷酸化才是走出Mitosis的最终原因。

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