Differential regulation of Rb family proteins and prohibitin during camptothecin-induced apoptosis
- 27 June 2002
- journal article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 21 (29), 4539-4548
- https://doi.org/10.1038/sj.onc.1205551
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.Keywords
This publication has 35 references indexed in Scilit:
- E2Fs regulate the expression of genes involved in differentiation, development, proliferation, and apoptosisGenes & Development, 2001
- Prohibitin, a potential tumor suppressor, interacts with RB and regulates E2F functionOncogene, 1999
- E2F1-induced apoptosis requires DNA binding but not transactivation and is inhibited by the retinoblastoma protein through direct interaction.Genes & Development, 1997
- Apoptosis is associated with cleavage of a 5 kDa fragment from RB which mimics dephosphorylation and modulates E2F bindingOncogene, 1997
- Tumor Induction and Tissue Atrophy in Mice Lacking E2F-1Cell, 1996
- E2F-1 Functions in Mice to Promote Apoptosis and Suppress ProliferationCell, 1996
- Differential Regulation of Retinoblastoma Protein Function by Specific Cdk Phosphorylation SitesPublished by Elsevier BV ,1996
- Cyclin A-kinase regulation of E2F-1 DNA binding function underlies suppression of an S phase checkpointCell, 1995
- Prohibitin Antiproliferative Activity and Lack of Heterozygosity in Immortalized Cell LinesExperimental Cell Research, 1995
- Stimulation of E2F1/DP1 transcriptional activity by MDM2 oncoproteinNature, 1995