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EMBO J. 2002 Jun 17;21(12):3019-28.

Prohibitin requires Brg-1 and Brm for the repression of E2F and cell growth.

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  • 1Boston University School of Medicine, Cancer Research Center, 715 Albany Street, Boston, MA 02118, USA. sw184@bu.edu

Abstract

E2F transcription factors play a major role in controlling mammalian cell cycle progression. We recently reported that a potential tumor suppressor, prohibitin, which interacts with retinoblastoma protein (Rb), regulates E2F function and this activity correlates with its growth-suppressive activity. We show here that prohibitin recruits Brg-1/Brm to E2F-responsive promoters, and that this recruitment is required for the repression of E2F-mediated transcription by prohibitin. Expression of a dominant-negative Brg-1 or Brm releases prohibitin-mediated repression of E2F and relieves prohibitin-mediated growth suppression. Although prohibitin associates with, and recruits, Brg-1 and Brm independently of Rb, prohibitin/Brg-1/Brm-mediated transcriptional repression requires Rb. A viral oncoprotein, SV40 large T antigen, can reverse prohibitin-mediated suppression of E2F-mediated gene transcription, and targets prohibitin through interruption of the association between prohibitin and Brg-1/Brm without affecting the prohibitin-E2F interaction.

PMID:
12065415
[PubMed - indexed for MEDLINE]
PMCID:
PMC126057
Free PMC Article
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