Cyclic, proteasome-mediated turnover of unliganded and liganded ERα on responsive promoters is an integral feature of estrogen signaling

被引：598

作者：

Reid, G ^{[1
]}

Hübner, MR ^{[1
]}

Métivier, R ^{[1
]}

Brand, H ^{[1
]}

Denger, S ^{[1
]}

Manu, D ^{[1
]}

Beaudouin, J ^{[1
]}

Ellenberg, J ^{[1
]}

Gannon, F ^{[1
]}

机构：

[1] European Mol Biol Lab, D-69117 Heidelberg, Germany

来源：

MOLECULAR CELL | 2003年 / 11卷 / 03期

关键词：

D O I：

10.1016/S1097-2765(03)00090-X

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 present an integrated model of hERalpha-mediated transcription where both unliganded and liganded receptors cycle on estrogen-responsive promoters. Using ChIP, FRAP, and biochemical analysis we evaluate hERalpha at several points in these cycles, establishing the ubiquitination status and subnuclear distribution of hERalpha, its mobility, the kinetics of transcriptional activation, and the cyclic recruitment of E3 ligases and the 19S regulatory component of the proteasome. These experiments, together with an evaluation of the inhibition of transcription and proteasome action, demonstrate that proteasome-mediated degradation and hERalpha-mediated transactivation are inherently linked and act to continuously turn over hERalpha on responsive promoters. Cyclic turnover of hERalpha permits continuous responses to changes in the concentration of estradiol.

引用

页码：695 / 707

页数：13

共 47 条

[1] Proteasome-mediated proteolysis of estrogen receptor: A novel component in autologous down-regulation [J].