C/EBPα通过直接抑制Cdk2和Cdk4来阻止细胞增殖。

C/EBPalpha arrests cell proliferation through direct inhibition of Cdk2 and Cdk4.

作者信息

Wang H, Iakova P, Wilde M, Welm A, Goode T, Roesler W J, Timchenko N A

机构信息

Department of Pathology and Huffington Center on Aging, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

出版信息

Mol Cell. 2001 Oct;8(4):817-28. doi: 10.1016/s1097-2765(01)00366-5.

DOI:10.1016/s1097-2765(01)00366-5

PMID:11684017

Abstract

The transcription factor CCAAT/enhancer binding protein alpha (C/EBPalpha) is a strong inhibitor of cell proliferation. We found that C/EBPalpha directly interacts with cdk2 and cdk4 and arrests cell proliferation by inhibiting these kinases. We mapped a short growth inhibitory region of C/EBPalpha between amino acids 175 and 187. This portion of C/EBPalpha is responsible for direct inhibition of cyclin-dependent kinases and causes growth arrest in cultured cells. C/EBPalpha inhibits cdk2 activity by blocking the association of cdk2 with cyclins. Importantly, the activities of cdk4 and cdk2 are increased in C/EBPalpha knockout livers, leading to increased proliferation. Our data demonstrate that the liver-specific transcription factor C/EBPalpha brings about growth arrest through direct inhibition of cdk2 and cdk4.

摘要

转录因子CCAAT/增强子结合蛋白α（C/EBPα）是细胞增殖的强效抑制剂。我们发现C/EBPα直接与细胞周期蛋白依赖性激酶2（cdk2）和细胞周期蛋白依赖性激酶4（cdk4）相互作用，并通过抑制这些激酶来阻止细胞增殖。我们确定了C/EBPα在氨基酸175至187之间的一个短的生长抑制区域。C/EBPα的这一部分负责直接抑制细胞周期蛋白依赖性激酶，并导致培养细胞生长停滞。C/EBPα通过阻止cdk2与细胞周期蛋白的结合来抑制cdk2活性。重要的是，在C/EBPα基因敲除的肝脏中，cdk4和cdk2的活性增加，导致细胞增殖增加。我们的数据表明，肝脏特异性转录因子C/EBPα通过直接抑制cdk2和cdk4导致生长停滞。