SWI/SNF complex interacts with tumor suppressor p53 and is necessary for the activation of p53-mediated transcription

Daeyoup Lee, Jin Woo Kim, Taegun Seo, Sun Gwan Hwang, Eui Ju Choi, Joonho Choe

Research output: Contribution to journalArticle

171 Citations (Scopus)

Abstract

The SWI/SNF complex is required for the transcription of several genes and has been shown to alter nucleosome structure in an ATP-dependent manner. The tumor suppressor protein p53 displays growth and transformation suppression functions that are frequently lost in mutant p53 proteins detected in various cancers. Using genetic and biochemical approaches, we show that several subunits of the human SWI/SNF complex bind to the tumor suppressor protein p53 in vivo and in vitro. The transactivation function of p53 is stimulated by overexpression of hSNF5 and BRG-1 and dominant forms of hSNF5 and BRG-1 repress p53-dependent transcription. Chromatin immunoprecipitation assay shows that hSNF5 and BRG-1 are recruited to a p53-dependent promoter in vivo. Overexpression of dominant negative forms of either hSNF5 or BRG-1 inhibited p53-mediated cell growth suppression and apoptosis. Molecular connection between p53 and the SWI/SNF complex implicates that (i) the SWI/SNF complex is necessary for p53-driven transcriptional activation, and (ii) the SWI/SNF complex plays an important role in p53-mediated cell cycle control.

Original languageEnglish
Pages (from-to)22330-22337
Number of pages8
JournalJournal of Biological Chemistry
Volume277
Issue number25
DOIs
Publication statusPublished - 2002 Jun 21
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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