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

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.