A CDK-independent function of mammalian Cks1:: Targeting of SCFSkp2 to the CDK inhibitor p27Kip1
A CDK-independent function of mammalian Cks1:: Targeting of SCFSkp2 to the CDK inhibitor p27Kip1
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DOI：
10.1016/s1097-2765(01)00210-6
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发表时间：
2001-03-01
期刊：
影响因子：
16
通讯作者：
Reed, SI
中科院分区：
文献类型：
--
作者：
Spruck, C;Strohmaier, H;Reed, SI
Cks/ su1蛋白与CDK/细胞周期蛋白复合物相关，但其确切功能尚不清楚。在这里，我们证明Cks1指导泛素介导的蛋白泛素连接酶（E3） SCFSkp2对cdk结合的底物p27（Kip1）的蛋白水解。Cks1与F box蛋白Skp2结合，是识别p27（Kip1）底物进行体内和体外泛素化的必要条件。利用纯化的重组蛋白，我们重建了p27（Kip1）的泛素化活性，并证明它依赖于Cks1。CKS1（-/-）小鼠异常小，来源于它们的细胞增殖能力差，特别是在有丝分裂原受限的条件下，可能是由于p27（Kip1）水平升高。
The Cks/Suc1 proteins associate with CDK/cyclin complexes, but their precise function(s) is not well defined. Here we demonstrate that Cks1 directs the ubiquitin-mediated proteolysis of the CDK-bound substrate p27(Kip1) by the protein ubiquitin ligase (E3) SCFSkp2. Cks1 associates with the F box protein Skp2 and is essential for recognition of the p27(Kip1) substrate for ubiquitination in vivo and in vitro. Using purified recombinant proteins, we reconstituted p27(Kip1) Ubiquitination activity and show that it is dependent on Cks1. CKS1(-/-) mice are abnormally small, and cells derived from them proliferate poorly, particularly under limiting mitogen conditions, possibly due to elevated levels of p27(Kip1).