C/EBPα arrests cell proliferation through direct inhibition of cdk2 and cdk4

被引：281

作者：

Wang, HM

Iakova, P

Wilde, M

Welm, A

Goode, T

Roesler, WJ

Timchenko, NA

机构：

[1] Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA

[2] Baylor Coll Med, Huffington Ctr Aging, Houston, TX 77030 USA

[3] Univ Saskatchewan, Dept Biochem, Saskatoon, SK S7N 5E5, Canada

来源：

MOLECULAR CELL | 2001年 / 8卷 / 04期

关键词：

D O I：

10.1016/S1097-2765(01)00366-5

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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

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收藏

页码：817 / 828

页数：12

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