Ligand-induced estrogen receptor alpha degradation by the proteasome: new actors?

In this perspective we consider new aspects of ligand-induced estrogen receptor alpha (ERalpha) degradation. What are the possible roles of CSN5/Jab1 and the CSN complex in this process? We compare hormone (estrogen) or pure antagonist (fulvestrant) induced degradation of ERalpha and review the effects of kinase-inhibitors and CRM1-dependent nuclear export on ERalpha degradation and transcription activation. A model for ERalpha action integrating these new actors is proposed and the relation between hormone-induced ERalpha degradation and transcription-activation is discussed.