Cdk11 Protein Through The Ubiquitin - Proteasome Pathway Inhibition On Estrogen Receptor Function

Estrogen receptorα(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 CDK11^p58 repressed ERαtranscriptional activity.And we further demonstrated that ERαprotein 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 ERαwas promoted by CDK11^p58.Furthermore,the interaction between ERαand 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 ERαand failed to reduce the ERαprotein level. These data identified a new negative regulatory protein of ERαand provided a new pathway by which CDK11^p58 negatively regulated cells.