Ligand-dependent switching of ubiquitin-proteasome pathways for estrogen receptor

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 ubiq...

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Published in:The EMBO journal 2004-12, Vol.23 (24), p.4813-4823
Main Authors: Tateishi, Yukiyo, Kawabe, Yoh-ichi, Chiba, Tomoki, Murata, Shigeo, Ichikawa, Ken, Murayama, Akiko, Tanaka, Keiji, Baba, Tadashi, Kato, Shigeaki, Yanagisawa, Junn
Format: Article
Language:English
Subjects:
Animals
Carrier Proteins - metabolism
Cell Line, Tumor
Cells, Cultured
Degradation
DNA-Binding Proteins
EMBO09
EMBO31
estrogen receptor
Estrogen Receptor alpha - chemistry
Estrogen Receptor alpha - genetics
Estrogen Receptor alpha - metabolism
Estrogens
Estrogens - metabolism
Fibroblasts - cytology
Fibroblasts - physiology
HSC70 Heat-Shock Proteins
HSP70 Heat-Shock Proteins - metabolism
Humans
Ligands
Mice
Mice, Knockout
nuclear receptors
Proteasome Endopeptidase Complex - metabolism
Protein Binding
Protein Conformation
Protein Folding
Quality control
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - metabolism
RNA, Small Interfering - metabolism
Signal Transduction - physiology
transcription
Transcription Factors
Ubiquitin - metabolism
Ubiquitin-Protein Ligases - genetics
Ubiquitin-Protein Ligases - metabolism
ubiquitination
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cited_by cdi_FETCH-LOGICAL-c6472-49c767f6394c89d81abffcc7dcd2f6a7bf3b61980313954c61bd986bd4e956033
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container_issue 24
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creator Tateishi, Yukiyo
Kawabe, Yoh-ichi
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Murata, Shigeo
Ichikawa, Ken
Murayama, Akiko
Tanaka, Keiji
Baba, Tadashi
Kato, Shigeaki
Yanagisawa, Junn
description 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.
doi_str_mv 10.1038/sj.emboj.7600472
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subjects Animals
Carrier Proteins - metabolism
Cell Line, Tumor
Cells, Cultured
Degradation
DNA-Binding Proteins
EMBO09
EMBO31
estrogen receptor
Estrogen Receptor alpha - chemistry
Estrogen Receptor alpha - genetics
Estrogen Receptor alpha - metabolism
Estrogens
Estrogens - metabolism
Fibroblasts - cytology
Fibroblasts - physiology
HSC70 Heat-Shock Proteins
HSP70 Heat-Shock Proteins - metabolism
Humans
Ligands
Mice
Mice, Knockout
nuclear receptors
Proteasome Endopeptidase Complex - metabolism
Protein Binding
Protein Conformation
Protein Folding
Quality control
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - metabolism
RNA, Small Interfering - metabolism
Signal Transduction - physiology
transcription
Transcription Factors
Ubiquitin - metabolism
Ubiquitin-Protein Ligases - genetics
Ubiquitin-Protein Ligases - metabolism
ubiquitination
title Ligand-dependent switching of ubiquitin-proteasome pathways for estrogen receptor
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