哺乳动物Cks1的一种不依赖细胞周期蛋白依赖性激酶（CDK）的功能：将SCF（Skp2）靶向细胞周期蛋白依赖性激酶抑制剂p27Kip1 。

A CDK-independent function of mammalian Cks1: targeting of SCF(Skp2) to the CDK inhibitor p27Kip1.

作者信息

Spruck C, Strohmaier H, Watson M, Smith A P, Ryan A, Krek T W, Reed S I

机构信息

The Scripps Research Institute, La Jolla, California 92037, USA.

出版信息

Mol Cell. 2001 Mar;7(3):639-50. doi: 10.1016/s1097-2765(01)00210-6.

DOI:10.1016/s1097-2765(01)00210-6

PMID:11463388

Abstract

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 p27Kip1 by the protein ubiquitin ligase (E3) SCF(Skp2). Cks1 associates with the F box protein Skp2 and is essential for recognition of the p27Kip1 substrate for ubiquitination in vivo and in vitro. Using purified recombinant proteins, we reconstituted p27Kip1 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 p27Kip1.

摘要

Cks/Suc1蛋白与细胞周期蛋白依赖性激酶（CDK）/细胞周期蛋白复合物相关联，但其确切功能尚未明确界定。在此我们证明，Cks1通过蛋白质泛素连接酶（E3）SCF（Skp2）引导泛素介导的CDK结合底物p27Kip1的蛋白水解。Cks1与F盒蛋白Skp2相关联，对于体内和体外识别用于泛素化的p27Kip1底物至关重要。我们使用纯化的重组蛋白重建了p27Kip1泛素化活性，并表明其依赖于Cks1。CKS1基因敲除小鼠异常小，源自它们的细胞增殖不良，特别是在有限的促分裂原条件下，这可能是由于p27Kip1水平升高所致。