P53-DEPENDENT REPRESSION OF CDK4 TRANSLATION IN TGF-BETA-INDUCED G(1) CELL-CYCLE ARREST

被引：161

作者：

EWEN, ME ^{[1
]}

OLIVER, CJ ^{[1
]}

SLUSS, HK ^{[1
]}

MILLER, SJ ^{[1
]}

PEEPER, DS ^{[1
]}

机构：

[1] HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA

来源：

GENES & DEVELOPMENT | 1995年 / 9卷 / 02期

关键词：

P53; CDK4; TGF-BETA; TRANSLATION; CELL CYCLE CONTROL;

D O I：

10.1101/gad.9.2.204

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Transforming growth factor beta 1 (TGF-beta 1) can cause a cell-cycle arrest in G(1). Inhibition of cyclin-dependent kinase 4 (cdk4) synthesis plays a significant role in the mechanism by which this cytokine causes G(1) growth arrest. Deregulated expression of cdk4 confers resistance to TGF-beta 1. Here, we show that TGF-beta 1 down regulates cdk4 expression by inhibiting its translation. Moreover, mutant p53 confers resistance to TGF-beta 1 by interfering with the down-regulation of cdk4 in response to the cytokine. In contrast, we demonstrate that wild-type p53 represses the translation of CDK4. Regulation of cdk4 synthesis by both p53 and TGF-beta 1 is mediated by the 5'-untranslated region of the CDK4 message. Thus, regulation of CDK4 translation may be involved in control of G(1) progression by p53.

引用

页码：204 / 217

页数：14

共 99 条

[1]

AJCHENBAUM F, 1992, J CELL BIOL, V268, P4113

[2] REGULATION OF G(1)/S TRANSITION BY CYCLIN-D2 AND CYCLIN-D3 IN HEMATOPOIETIC-CELLS [J].