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

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.
Mesh Terms:
Antigens, Polyomavirus Transforming, Antineoplastic Agents, Cell Cycle Proteins, Cell Division, Cell Line, DNA Helicases, DNA-Binding Proteins, Drosophila Proteins, E2F Transcription Factors, Gene Expression Regulation, Humans, Nuclear Proteins, Promoter Regions, Genetic, Proteins, Repressor Proteins, Trans-Activators, Transcription Factors, Transcription, Genetic
EMBO J.
Date: Jun. 17, 2002
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