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

Hisashi Masuyama, Yuji Hiramatsu


33 被引用数 (Scopus)


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.

ジャーナルJournal of Biological Chemistry
出版ステータスPublished - 3月 26 2004

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 細胞生物学


「Involvement of Suppressor for Gal 1 in the Ubiquitin/Proteasome-mediated Degradation of Estrogen Receptors」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。