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  • Original Paper
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Prohibitin, a potential tumor suppressor, interacts with RB and regulates E2F function

Oncogene volume 18, pages 3501–3510 (1999)Cite this article

Abstract

The retinoblastoma tumor suppressor protein and its family members, p107 and p130, are major regulators of the mammalian cell cycle. They exert their growth suppressive effects at least in part by binding the E2F family of transcription factors and inhibiting their transcriptional activity. Agents that disrupt the interaction between Rb family proteins and E2F promote cell proliferation. Here we describe the characterization of a novel interaction between Rb family proteins and a potential tumor suppressor protein, prohibitin. Prohibitin physically interacts with all three Rb family proteins in vitro and in vivo, and was very effective in repressing E2F-mediated transcription. Prohibitin could inhibit the activity of E2Fs 1, 2, 3, 4 and 5, but could not affect the activity of promoters lacking an E2F site. Surprisingly, prohibitin-mediated repression of E2F could not be reversed by adenovirus E1A protein. A prohibitin mutant that could not bind to Rb was impaired in its ability to repress E2F activity and inhibit cell proliferation. We believe that prohibitin is a novel regulator of E2F activity that responds to specific signaling cascades.

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Acknowledgements

We thank Dr J Keith McClung for providing the prohibitin cDNA and antibodies, as well as for helpful suggestions. This study was supported by a grant from the NCI (CA63136). SPC is a recipient of the Irma-Hirschl Trust Research Award.

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Authors and Affiliations

  1. Department of Pathology, College of Physicians and Surgeons, Columbia University, 630W 168th Street, New York, 10032, NY, USA

    Sheng Wang, Niharika Nath & Srikumar Chellappan

  2. Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, 630W 168th Street, New York, 10032, NY, USA

    Matthew Adlam

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Wang, S., Nath, N., Adlam, M. et al. Prohibitin, a potential tumor suppressor, interacts with RB and regulates E2F function. Oncogene 18, 3501–3510 (1999). https://doi.org/10.1038/sj.onc.1202684

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