Turnover of cyclin E by the ubiquitin-proteasome pathway is regulated by cdk2 binding and cyclin phosphorylation
Turnover of cyclin E by the ubiquitin-proteasome pathway is regulated by cdk2 binding and cyclin phosphorylation
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DOI：
10.1101/gad.10.16.1979
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发表时间：
1996-08-15
影响因子：
10.5
通讯作者：
Roberts, JM
中科院分区：
文献类型：
--
作者：
Clurman, BE;Sheaff, RJ;Roberts, JM
细胞周期蛋白E是哺乳动物G（1）细胞周期蛋白，它是进入S期所必需的，也是进入S期的速率限制因子。细胞周期蛋白E的表达是周期性的，在G（1）-S转变时达到峰值，然后随着S期的进展而衰减。为了了解细胞周期蛋白E周期性的机制，我们研究了细胞周期蛋白E降解的调节。我们发现，细胞周期蛋白E降解的泛素-蛋白酶体系统，这种降解是由两个cdk 2结合和cdk 2催化活性。游离细胞周期蛋白E容易被蛋白酶体泛素化和降解。与cdk 2结合可保护细胞周期蛋白E不被泛素化，这种保护作用在涉及细胞周期蛋白E自身磷酸化的过程中被cdk 2活性逆转。这些数据与一个模型最为一致，在该模型中，cdk 2活性通过促进细胞周期蛋白E-cdk 2复合物的分解来启动细胞周期蛋白E的降解，随后是游离细胞周期蛋白E的泛素化和降解。
Cyclin E is a mammalian G(1) cyclin that is both required and rate limiting for entry into S phase. The expression of cyclin E is periodic, peaking at the G(1)-S transition and then decaying as S phase progresses. To understand the mechanisms underlying cyclin E periodicity, we have investigated the regulation of cyclin E degradation. We find that cyclin E is degraded by the ubiquitin-proteasome system, and that this degradation is regulated by both cdk2 binding and cdk2 catalytic activity. Free cyclin E is readily ubiquitinated and degraded by the proteasome. Binding to cdk2 protects cyclin E from ubiquitination, and this protection is reversed by cdk2 activity in a process that involves phosphorylation of cyclin E itself. The data are most consistent with a model in which cdk2 activity initiates cyclin E degradation by promoting the disassembly of cyclin E-cdk2 complexes, followed by the ubiquitination and degradation of free cyclin E.