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

ABSTRACT: Recent evidence indicates that the transactivation of estrogen receptor alpha (ERalpha) requires estrogen-dependent receptor ubiquitination and degradation. Here we show that estrogen-unbound (unliganded) ERalpha is also ubiquitinated and degraded through a ubiquitin-proteasome pathway. To investigate this ubiquitin-proteasome pathway, we purified the ubiquitin ligase complex for unliganded ERalpha and identified a protein complex containing the carboxyl terminus of Hsc70-interacting protein (CHIP). CHIP preferentially bound to misfolded ERalpha and ubiquitinated it to induce degradation. Ligand binding to the receptor induced the dissociation of CHIP from ERalpha. In CHIP-/- cells, the degradation of unliganded ERalpha was abrogated; however, estrogen-induced degradation was observed to the same extent as in CHIP+/+ cells. Our findings suggest that ERalpha is regulated by two independent ubiquitin-proteasome pathways, which are switched by ligand binding to ERalpha. One pathway is necessary for the transactivation of the receptor and the other is involved in the quality control of the receptor.

SUBMITTER: Tateishi Y

PROVIDER: S-EPMC535086 | biostudies-other | 2004 Dec

REPOSITORIES: biostudies-other

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

Tateishi Yukiyo Y Kawabe Yoh-ichi Y Chiba Tomoki T Murata Shigeo S Ichikawa Ken K Murayama Akiko A Tanaka Keiji K Baba Tadashi T Kato Shigeaki S Yanagisawa Junn J

The EMBO journal 20041111 24

Recent evidence indicates that the transactivation of estrogen receptor alpha (ERalpha) requires estrogen-dependent receptor ubiquitination and degradation. Here we show that estrogen-unbound (unliganded) ERalpha is also ubiquitinated and degraded through a ubiquitin-proteasome pathway. To investigate this ubiquitin-proteasome pathway, we purified the ubiquitin ligase complex for unliganded ERalpha and identified a protein complex containing the carboxyl terminus of Hsc70-interacting protein (CH ...[more]

PMID: 15538384

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

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

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