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有丝分裂蛋白酶解抑制剂对细胞周期蛋白B降解系统的调控

Regulation of the cyclin B degradation system by an inhibitor of mitotic proteolysis.

作者信息

Vorlaufer E, Peters J M

机构信息

Research Institute of Molecular Pathology, A-1030 Vienna, Austria.

出版信息

Mol Biol Cell. 1998 Jul;9(7):1817-31. doi: 10.1091/mbc.9.7.1817.

DOI:10.1091/mbc.9.7.1817
PMID:9658173
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC25421/
Abstract

The initiation of anaphase and exit from mitosis depend on the anaphase-promoting complex (APC), which mediates the ubiquitin-dependent proteolysis of anaphase-inhibiting proteins and mitotic cyclins. We have analyzed whether protein phosphatases are required for mitotic APC activation. In Xenopus egg extracts APC activation occurs normally in the presence of protein phosphatase 1 inhibitors, suggesting that the anaphase defects caused by protein phosphatase 1 mutation in several organisms are not due to a failure to activate the APC. Contrary to this, the initiation of mitotic cyclin B proteolysis is prevented by inhibitors of protein phosphatase 2A such as okadaic acid. Okadaic acid induces an activity that inhibits cyclin B ubiquitination. We refer to this activity as inhibitor of mitotic proteolysis because it also prevents the degradation of other APC substrates. A similar activity exists in extracts of Xenopus eggs that are arrested at the second meiotic metaphase by the cytostatic factor activity of the protein kinase mos. In Xenopus eggs, the initiation of anaphase II may therefore be prevented by an inhibitor of APC-dependent ubiquitination.

摘要

后期的启动和有丝分裂的退出依赖于后期促进复合物(APC),该复合物介导后期抑制蛋白和有丝分裂周期蛋白的泛素依赖性蛋白水解。我们分析了有丝分裂APC激活是否需要蛋白磷酸酶。在非洲爪蟾卵提取物中,APC激活在存在蛋白磷酸酶1抑制剂的情况下正常发生,这表明在几种生物体中由蛋白磷酸酶1突变引起的后期缺陷并非由于未能激活APC。与此相反,蛋白磷酸酶2A的抑制剂如冈田酸可阻止有丝分裂周期蛋白B蛋白水解的启动。冈田酸诱导一种抑制周期蛋白B泛素化的活性。我们将这种活性称为有丝分裂蛋白水解抑制剂,因为它也能阻止其他APC底物的降解。在被蛋白激酶mos的细胞静止因子活性阻滞在第二次减数分裂中期的非洲爪蟾卵提取物中存在类似的活性。因此,在非洲爪蟾卵中,后期II的启动可能会被一种APC依赖性泛素化抑制剂所阻止。

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