Prohibitin interacts with RNF2 and regulates E2F1 function via dual pathways

D. Choi, S. J. Lee, S. Hong, I. H. Kim, S. Kang

Research output: Contribution to journalArticlepeer-review

44 Citations (Scopus)


Prohibitin, a tumor suppresser protein, plays an important role in the transcriptional regulation of various genes involved in cell-cycle control and proliferation. Recent studies have reported that the growth-suppressive property of the prohibitin protein is exhibited in its physical interaction with E2F family proteins and its subsequent repression of their transcriptional activity. Herein, we report that prohibitin interacts with RING finger protein 2 (RNF2), a member of the PcG (polycomb-group) family of proteins, and that the two proteins regulate the activity of E2F1 via dual pathways: the direct, prohibitin-mediated pathway and the indirect, p16-mediated pathway of E2F1 transcriptional regulation. Co-immunoprecipitation experiments showed that endogenous prohibitin interacts with endogenous RNF2. Interestingly, the expressed amounts of RNF2 and prohibitin were interdependently affected at the post-translational level. Furthermore, the depletion of either endogenous RNF2 or prohibitin using the RNA interference technique increased the level of p16 protein expression, resulting in a decrease in the transcriptional activity of E2F1 via the p16-CDK4-Rb pathway. In addition, chromatin immunoprecipitation assays showed that RNF2 was recruited to E2F1-response promoters along with prohibitin to inhibit the transcriptional activity of E2F1. Cell proliferation was also regulated by the prohibitin-RNF2 interaction. These results suggest that the RNF2-prohibitin complex regulates the activity of E2F1 via dual pathways.

Original languageEnglish
Pages (from-to)1716-1725
Number of pages10
Issue number12
Publication statusPublished - 2008 Mar 13

Bibliographical note

Funding Information:
This work was supported by the Korea Research Foundation grant funded by the Korean Government (MOEHRD) (KRF-2005-C00350) and Korea University (K0401401).


  • Cell cycle
  • E2F1
  • Prohibitin
  • RNF2
  • p16

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research


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