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.
Wang
Sheng
S
Boston University School of Medicine, Cancer Research Center, 715 Albany Street, Boston, MA 02118, USA. sw184@bu.edu
Zhang
Baohua
B
Faller
Douglas V
DV
D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism; D000970:Antineoplastic Agents / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology*; D002460:Cell Line; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000378:metabolism; D029721:Drosophila Proteins; D050684:E2F Transcription Factors; D005786:Gene Expression Regulation; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D000091402:Prohibitins; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D000952:Antigens, Polyomavirus Transforming; D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D050684:E2F Transcription Factors; D009687:Nuclear Proteins; D000091402:Prohibitins; D011506:Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C086469:brm protein, Drosophila; C084108:SMARCA4 protein, human; D004265:DNA Helicases