Transcriptional activation by the oestrogen receptor α is modulated through inhibition of cyclin-dependent kinases

被引：23

作者：

Redeuilh, G ^{[1
]}

Attia, A ^{[1
]}

Mester, J ^{[1
]}

Sabbah, M ^{[1
]}

机构：

[1] Hop St Antoine, INSERM, U482, F-75571 Paris 12, France

来源：

ONCOGENE | 2002年 / 21卷 / 37期

关键词：

oestrogen receptor; p21(waf1); cell cycle; coactivators; cyclin-dependent kinases;

D O I：

10.1038/sj.onc.1205753

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：

We have investigated the interaction between the expression of p21(WAF1/CIP1/SDI1), a stoichiometric inhibitor of Cdk, and the transcriptional activity of the oestrogen receptor alpha (ERalpha). Transient transfection experiments demonstrated that the expression of p21(WAF1/CIP1/SDI1) amplified the transcriptional activation by ERalpha. A dominant negative mutant of Cdk2 also enhanced the ERa transcriptional activity, indicating that the underlying mechanism relies on the inhibition of Cdk2 activity and cell cycle arrest. In agreement with this conclusion, experiments with p21(WAF1/CIP1/SDI1) mutants demonstrated that the domain involved in the binding of p21(WAF1/CIP1/SDI1) to Cdks was indispensable for the modulation of ERa activity. In addition, we show that expression of p21(WAF1/CIP1/SDI1) alleviates the block on CBP function mediated by Cdk2 and in turn stimulates transcriptional activation by ERalpha in a CBP-histone acetyltransferase (HAT)-dependent manner. These results suggest a novel mechanism by which p21(WAF1/CIP1/SDI1) functions as an enhancer of ERalpha activity through the modulation of CBP function.

引用

页码：5773 / 5782

页数：10

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