Rb and prohibitin target distinct regions of E2F1 for repression and respond to different upstream signals.

E2F transcription factor is subject to stringent regulation by a variety of molecules. We recently observed that prohibitin, a potential tumor suppressor protein, binds to the retinoblastoma (Rb) protein and represses E2F transcriptional activity. Here we demonstrate that prohibitin requires the marked box region of E2F for repression; further, prohibitin ...
can effectively inhibit colony formation induced by overexpression of E2F1 in T47D cells. Prohibitin was also found to interact with the signaling kinase c-Raf-1, and Raf-1 could effectively reverse prohibitin-mediated repression of E2F activity. Agents such as E1A, p38 kinase, and cyclins D and E had no effect on prohibitin-mediated repression of E2F1, but all of these molecules could reverse Rb function. Similarly, stimulation of the immunoglobulin M signaling pathway in Ramos cells could inactivate prohibitin, but this had no effect on Rb function. Serum stimulation of quiescent Ramos cells inactivated Rb and prohibitin with different kinetics; further, while the serum-dependent inactivation of Rb was dependent on cyclin-dependent kinase activity, the inactivation of prohibitin was not. We believe that prohibitin is a novel regulator of E2F function which channels specific signaling cascades to the cell cycle regulatory machinery.
Mesh Terms:
Binding Sites, Carrier Proteins, Cell Cycle Proteins, Colony-Forming Units Assay, Cyclin-Dependent Kinases, DNA-Binding Proteins, E2F Transcription Factors, E2F1 Transcription Factor, Gene Expression Regulation, Protein Binding, Proteins, Proto-Oncogene Proteins c-raf, Receptor Cross-Talk, Receptors, Fc, Recombinant Fusion Proteins, Repressor Proteins, Retinoblastoma Protein, Retinoblastoma-Binding Protein 1, Signal Transduction, Transcription Factors, Transcription, Genetic
Mol. Cell. Biol.
Date: Nov. 01, 1999
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