Involvement of Suppressor for Gal 1 in the Ubiquitin/Proteasome-mediated Degradation of Estrogen Receptors

Hisashi Masuyama, Yuji Hiramatsu

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

The proteasome-mediated pathway involves the degradation of several nuclear receptors. Previously we demonstrated that the interaction between the suppressor for Gal 1 (SUG1) and nuclear receptors, the vitamin D receptor, or the pregnane X receptor was involved in proteasome-mediated degradation. In our recent experiments, we examined the potential role of SUG1 in the proteasome-mediated degradation of estrogen receptors (ER)α and -β. Both ERs interacted with SUG1 in a ligand-dependent manner. Functionally, the overexpression of SUG1 inhibited both ERα- and ERβ-mediated transcription in the presence of ligands. Transient expression studies demonstrated that the overexpression of wild-type SUG1 generated proteolytic fragments of both ERs and that these products were blocked by a proteasome inhibitor. The overexpression of SUG1 also enhanced the formation of ubiquitinated proteins of both ERs in the presence of ligand. On the other hand, bisphenol A (BSA), which activated ER-mediated transcription, did not enhance the interaction between ERβ and SUG1. Furthermore, the degradation of ERβ was much slower in the presence of BSA than in the presence of estradiol or phthalate, which is another endocrine-disrupting chemical. Also, BSA had no effect on the formation of proteolytic fragments of ERβ, and neither did it have any effect on the ubiquitination of ERβ. These findings indicate that the ubiquitin/proteasome-mediated degradation of both ER proteins may involve the interaction of SUG1 with both ERs. Moreover, BSA strongly blocked the ubiquitination and degradation of ERβ compared with estradiol, suggesting that BSA may affect the ERβ-mediated transcription of target genes by inhibiting ERβ degradation.

Original languageEnglish
Pages (from-to)12020-12026
Number of pages7
JournalJournal of Biological Chemistry
Volume279
Issue number13
DOIs
Publication statusPublished - Mar 26 2004

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Proteasome Endopeptidase Complex
Ubiquitin
Estrogen Receptors
Degradation
Transcription
Ubiquitination
Cytoplasmic and Nuclear Receptors
Ligands
Estradiol
Ubiquitinated Proteins
Endocrine Disruptors
Calcitriol Receptors
Proteasome Inhibitors
Genes
bisphenol A

ASJC Scopus subject areas

  • Biochemistry

Cite this

Involvement of Suppressor for Gal 1 in the Ubiquitin/Proteasome-mediated Degradation of Estrogen Receptors. / Masuyama, Hisashi; Hiramatsu, Yuji.

In: Journal of Biological Chemistry, Vol. 279, No. 13, 26.03.2004, p. 12020-12026.

Research output: Contribution to journalArticle

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