The catalytic subunit of the proteasome is engaged in the entire process of estrogen receptor-regulated transcription

Hua Zhang, Luyang Sun, Jing Liang, Wenhua Yu, Ying Zhang, Yan Wang, Yupeng Chen, Ruifang Li, Xiaojing Sun, Yongfeng Shang

Research output: Contribution to journalArticle

67 Scopus citations

Abstract

The ubiquitin-proteasome system plays an important role in a variety of cellular functions by means of its proteolytic activity. Interestingly, recent studies have indicated that the proteasome components are also integral parts of transcription complexes. In genome-wide screening for steroid receptor coactivator (SRC)-interacting proteins using yeast two-hybrid system, we found that the 20S proteasome β subunit LMP2 (Low Molecular mass Polypeptide 2) interacts directly with the SRC coactivators. We showed that LMP2 is required for estrogen receptor (ER)-mediated gene transcription and for estrogen-stimulated cell cycle progression. We found that LMP2-associated proteasome is recruited to the entire sequence of ER target genes, implicating a role for the proteasome in both transcription initiation and elongation. We demonstrated that the recruitment of LMP2 by SRC coactivators is necessary for cyclic association of ER-regulated transcription complexes on ER targets. These results revealed a mechanism by which the proteasome machinery is recruited in ER-mediated gene transcription. Our experiments also provided evidence implicating SRC coactivators in gene transcription elongation.

Original languageEnglish (US)
Pages (from-to)4223-4233
Number of pages11
JournalEMBO Journal
Volume25
Issue number18
DOIs
Publication statusPublished - Sep 20 2006

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Keywords

  • Coactivator
  • Estrogen receptor
  • Gene transcription
  • LMP2
  • Proteasome

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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