Kinase-independent function of cyclin E
Kinase-independent function of cyclin E
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DOI：
10.1016/j.molcel.2006.11.029
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发表时间：
2007-01-12
期刊：
影响因子：
16
通讯作者：
Sicinski, Piotr
中科院分区：
文献类型：
--
作者：
Geng, Yan;Lee, Young-Mi;Sicinski, Piotr
e型细胞周期蛋白被认为通过激活细胞周期蛋白依赖性激酶（主要是CDK2）来驱动细胞周期进程。我们之前发现，在G(0) -> S期过程中，cyclin E-null细胞无法将MCM解旋酶整合到DNA预复制复合体中。我们现在报道，一个激酶缺陷的周期蛋白E突变体可以部分恢复MCM装载和周期蛋白E缺失细胞的S期进入。我们发现细胞周期蛋白E在G(0) -> S过程中被装载到染色质上。在缺乏细胞周期蛋白E的情况下，CDT1通常装载到染色质上，而MCM则不是，这表明细胞周期蛋白E在CDT1和MCM装载之间起作用。我们观察到细胞周期蛋白E与CDT1和mcm的物理关联。我们提出周期蛋白E通过与CDT1和MCM的物理相互作用，以激酶无关的方式促进MCM的加载。我们的工作表明，除了它们作为CDK激活剂的功能外，e细胞周期蛋白在细胞周期进程中发挥激酶无关的功能。
E-type cyclins are thought to drive cell-cycle progression by activating cyclin-dependent kinases, primarily CDK2. We previously found that cyclin E-null cells failed to incorporate MCM helicase into DNA prereplication complex during G(0) -> S phase progression. We now report that a kinase-deficient cyclin E mutant can partially restore MCM loading and S phase entry in cyclin E-null cells. We found that cyclin E is loaded onto chromatin during G(0) -> S progression. In the absence of cyclin E, CDT1 is normally loaded onto chromatin, whereas MCM is not, indicating that cyclin E acts between CDT1 and MCM loading. We observed a physical association of cyclin E with CDT1 and with MCMs. We propose that cyclin E facilitates MCM loading in a kinase-independent fashion, through physical interaction with CDT1 and MCM. Our work indicates that-in addition to their function as CDK activators-E cyclins play kinase-independent functions in cell-cycle progression.