Repression of estrogen receptor alpha by CDK11p58 through promoting its ubiquitin-proteasome degradation.
Estrogen receptor alpha (ERalpha) is a ligand-dependent transcription factor that mediates physiological responses to 17beta-estradiol (E(2)). These responses of cells to estrogen are regulated in part by degradation of ERalpha. In this report, we found that CDK11(p58) repressed ERalpha transcriptional activity. And we further demonstrated that ERalpha protein level was down-regulated by CDK11(p58) in mammalian cells in a ligand independent manner. This effect could be abrogated by treatment with proteasome inhibitor MG132. Our results indicated that the ubiquitin/proteasome-mediated degradation of ERalpha was promoted by CDK11(p58). Furthermore, the interaction between ERalpha and CDK11(p58) was detected. This interaction was necessary for the polyubiquitination and degradation of ERalpha. On the contrary, the other isoform of CDK11, CDK11(p110) and the kinase dead mutant of CDK11(p58), D224N, did not associate with ERalpha and failed to reduce the ERalpha protein level. These data identified a new negative regulatory protein of ERalpha and provided a new pathway by which CDK11(p58) negatively regulated cells.
Wang
Yanlin
Y
Gene Research Center, Shanghai Medical College and Institutes of Biomedical, Shanghai 200032, People's Republic of China.
Zong
Hongliang
H
Chi
Yayun
Y
Hong
Yi
Y
Yang
Yanzhong
Y
Zou
Weiying
W
Yun
Xiaojing
X
Gu
Jianxin
J
D000818:Animals; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D056743:Cyclin D3; D016213:Cyclins / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D012097:Repressor Proteins / Q000378:metabolism*; D014158:Transcription, Genetic; D025801:Ubiquitin / Q000378:metabolism*
C534696:CCND3 protein, human; D056743:Cyclin D3; D016213:Cyclins; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D012097:Repressor Proteins; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex