Differential regulation of Rb family proteins and prohibitin during camptothecin-induced apoptosis.
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.
Fusaro
Gina
G
Department of Pathology, College of Physicians and Surgeons, Columbia University, 630 W 168th St, New York, NY 10032, USA.
Wang
Sheng
S
Chellappan
Srikumar
S
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002166:Camptothecin / Q000494:pharmacology*; D018797:Cell Cycle Proteins; D002460:Cell Line; D019927:Cyclin E / Q000378:metabolism; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D000091402:Prohibitins; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects; D014407:Tumor Cells, Cultured
D018797:Cell Cycle Proteins; D019927:Cyclin E; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D000091402:Prohibitins; D011506:Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D014157:Transcription Factors; D002166:Camptothecin