Repression of estrogen receptor alpha by CDK11^p58 through promoting its ubiquitin-proteasome degradation

Estrogen receptor α (ERα) is a ligand-dependent transcription factor that mediates physiological responses to 17β-estradiol (E ₂). These responses of cells to estrogen are regulated in part by degradation of ERα. In this report, we found that CDK11^p58 repressed ERα transcriptional activity. And we further demonstrated that ERα 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 ERα was promoted by CDK11^p58. Furthermore, the interaction between ERα and CDK11^p58 was detected. This interaction was necessary for the polyubiquitination and degradation of ERα. On the contrary, the other isoform of CDK11, CDK11^p110 and the kinase dead mutant of CDK11 ^p58, 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 CDK11^p58 negatively regulated cells.