Repression of Estrogen Receptor alpha by CDK11p58 Through Promoting its Ubiquitin–Proteasome Degradation

• Published in: Journal of biochemistry (Tokyo) 2009-03, Vol.145 (3), p.331-343
• Main Authors: Wang, Yanlin, Zong, Hongliang, Chi, Yayun, Hong, Yi, Yang, Yanzhong, Zou, Weiying, Yun, Xiaojing, Gu, Jianxin
• Format: Article
• Language: English
• Subjects: Animals; CDK11p58; Cell Line, Tumor; Cercopithecus aethiops; COS Cells; Cyclin D3; Cyclins - metabolism; degradation; Estrogen Receptor alpha - metabolism; estrogen receptor α; Humans; Proteasome Endopeptidase Complex - metabolism; Protein Binding; Protein Processing, Post-Translational; Repressor Proteins - metabolism; steroid; Transcription, Genetic; Ubiquitin - metabolism; ubiquitin–proteasome
• ISSN: 0021-924X; 1756-2651
• DOI: 10.1093/jb/mvn177

Estrogen receptor α (ERα) is a ligand-dependent transcription factor that mediates physiological responses to 17β-estradiol (E2). These responses of cells to estrogen are regulated in part by degradation of ERα. In this report, we found that CDK11p58 repressed ERα transcriptional activity. And we further demonstrated that ERα protein level was down-regulated by CDK11p58 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 ERα was promoted by CDK11p58. Furthermore, the interaction between ERα and CDK11p58 was detected. This interaction was necessary for the polyubiquitination and degradation of ERα. On the contrary, the other isoform of CDK11, CDK11p110 and the kinase dead mutant of CDK11p58, D224N, did not associate with ERα and failed to reduce the ERα protein level. These data identified a new negative regulatory protein of ERα and provided a new pathway by which CDK11p58 negatively regulated cells.