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

• Published in: The EMBO journal 2002-06, Vol.21 (12), p.3019-3028
• Main Authors: Wang, Sheng, Zhang, Baohua, Faller, Douglas V.
• Format: Article
• Language: English
• Subjects: Antigens, Polyomavirus Transforming - metabolism; Antineoplastic Agents - metabolism; Brg-1; Brm; Cell Cycle Proteins - metabolism; Cell Division - physiology; Cell Line; DNA Helicases; DNA-Binding Proteins - metabolism; Drosophila Proteins; E2F; E2F Transcription Factors; EMBO06; EMBO09; Gene Expression Regulation; Humans; Nuclear Proteins - metabolism; prohibitin; Promoter Regions, Genetic; Proteins - metabolism; Repressor Proteins - metabolism; SV40 T antigen; Trans-Activators - metabolism; Transcription Factors - metabolism; Transcription, Genetic
• ISSN: 0261-4189; 1460-2075; 1460-2075
• DOI: 10.1093/emboj/cdf302

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.