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Differential regulation of Rb family proteins and prohibitin during camptothecin-induced apoptosis

Oncogene volume 21, pages 4539–4548 (2002)Cite this article

Abstract

Prohibitin, a potential tumor suppressor, is known to induce growth suppression and repress E2F-mediated transcription. These growth regulatory functions of prohibitin require a physical interaction with the Rb protein. We now find that prohibitin protects cells from apoptosis mediated by camptothecin, a topoisomerase I inhibitor. Camptothecin treatment of Ramos B cells leads to the degradation of Rb protein and phosphorylation of its family members, p107 and p130. This correlates with an increase in the levels of cyclin E as well as the kinase activity associated with it. Inactivation of Rb leads to the dissociation and release of free E2F. We find also that E2F activity is induced upon camptothecin treatment, but this increase is absent in prohibitin overexpressing cells. It thus appears that prohibitin may be inhibiting apoptosis by downregulating E2F activity when Rb family members are inactive.

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Acknowledgements

This study was supported by the grant CA77301 from the NCI. GF is a recipient of a DOD student fellowship for breast cancer research (DAMD 17-01-1-0215).

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  1. Sheng Wang

    Present address: Boston University School of Medicine, Cancer Research Center, R-906, Boston, 02118, Massachusetts, MA, USA

Authors and Affiliations

  1. Department of Interdisciplinary Oncology, H Lee Moffit Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, 33612, Florida, FL, USA

    Srikumar Chellappan

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

    Gina Fusaro

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  1. Gina Fusaro
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Correspondence to Srikumar Chellappan.

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Fusaro, G., Wang, S. & Chellappan, S. Differential regulation of Rb family proteins and prohibitin during camptothecin-induced apoptosis. Oncogene 21, 4539–4548 (2002). https://doi.org/10.1038/sj.onc.1205551

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