Geminin的非蛋白水解失活需要CDK依赖的泛素化。
Non-proteolytic inactivation of geminin requires CDK-dependent ubiquitination.
作者信息
Li Anatoliy, Blow J Julian
机构信息
Wellcome Trust Biocentre, University of Dundee, Dow Street, Dundee DD1 5EH, UK.
出版信息
Nat Cell Biol. 2004 Mar;6(3):260-7. doi: 10.1038/ncb1100. Epub 2004 Feb 8.
Abstract
In late mitosis and G1, a complex of the essential initiation proteins Mcm2-7 are assembled onto replication origins to 'license' them for initiation. At other times licensing is inhibited by cyclin-dependent kinases (CDKs) and geminin, thus ensuring that origins fire only once per cell cycle. Here we show that, paradoxically, CDKs are also required to inactivate geminin and activate the licensing system. On exit from metaphase in Xenopus laevis egg extracts, CDK-dependent activation of the anaphase-promoting complex (APC/C) results in the transient polyubiquitination of geminin. This ubiquitination triggers geminin inactivation without requiring ubiquitin-dependent proteolysis, and is essential for replication origins to become licensed. This reveals an unexpected role for CDKs and ubiquitination in activating chromosomal DNA replication.
摘要
在有丝分裂后期和G1期，必需的起始蛋白Mcm2 - 7复合物组装到复制起点上，使其获得起始“许可”。在其他时期，复制许可受到细胞周期蛋白依赖性激酶（CDK）和geminin的抑制，从而确保每个细胞周期中复制起点只启动一次。令人惊讶的是，我们在此表明，CDK对于使geminin失活并激活许可系统也是必需的。在非洲爪蟾卵提取物中从中期退出时，CDK依赖的后期促进复合物（APC/C）激活导致geminin的瞬时多聚泛素化。这种泛素化触发geminin失活，而无需泛素依赖性蛋白水解，并且对于复制起点获得许可至关重要。这揭示了CDK和泛素化在激活染色体DNA复制中意想不到的作用。
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