Ligand-dependent switching of ubiquitin–proteasome pathways for estrogen receptor
AUTOR(ES)
Tateishi, Yukiyo
FONTE
Nature Publishing Group
RESUMO
Recent evidence indicates that the transactivation of estrogen receptor α (ERα) requires estrogen-dependent receptor ubiquitination and degradation. Here we show that estrogen-unbound (unliganded) ERα is also ubiquitinated and degraded through a ubiquitin–proteasome pathway. To investigate this ubiquitin–proteasome pathway, we purified the ubiquitin ligase complex for unliganded ERα and identified a protein complex containing the carboxyl terminus of Hsc70-interacting protein (CHIP). CHIP preferentially bound to misfolded ERα and ubiquitinated it to induce degradation. Ligand binding to the receptor induced the dissociation of CHIP from ERα. In CHIP−/− cells, the degradation of unliganded ERα was abrogated; however, estrogen-induced degradation was observed to the same extent as in CHIP+/+ cells. Our findings suggest that ERα is regulated by two independent ubiquitin–proteasome pathways, which are switched by ligand binding to ERα. One pathway is necessary for the transactivation of the receptor and the other is involved in the quality control of the receptor.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=535086Documentos Relacionados
- Regulation of nicotinic receptor expression by the ubiquitin–proteasome system
- Ligand-dependent repression of the erythroid transcription factor GATA-1 by the estrogen receptor.
- The Ubiquitin-Proteasome Pathway and Plant Development
- Degradation of the Met tyrosine kinase receptor by the ubiquitin-proteasome pathway.
- Inhibition of the ubiquitin-proteasome system in Alzheimer's disease