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Proapoptotic Function of the Retinoblastoma Tumor Suppressor Protein

Author(s)
Ianari, Alessandra; Natale, Tiziana; Calo, Eliezer; Ferretti, Elisabetta; Alesse, Edoardo; Screpanti, Isabella; Haigis, Kevin M.; Gulino, Alberto; Lees, Jacqueline; ... Show more Show less
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Abstract
The retinoblastoma protein (pRB) tumor suppressor blocks cell proliferation by repressing the E2F transcription factors. This inhibition is relieved through mitogen-induced phosphorylation of pRB, triggering E2F release and activation of cell-cycle genes. E2F1 can also activate proapoptotic genes in response to genotoxic or oncogenic stress. However, pRB's role in this context has not been established. Here we show that DNA damage and E1A-induced oncogenic stress promote formation of a pRB-E2F1 complex even in proliferating cells. Moreover, pRB is bound to proapoptotic promoters that are transcriptionally active, and pRB is required for maximal apoptotic response in vitro and in vivo. Together, these data reveal a direct role for pRB in the induction of apoptosis in response to genotoxic or oncogenic stress.
Date issued
2009-03
URI
http://hdl.handle.net/1721.1/84669
Department
Massachusetts Institute of Technology. Department of Biology; Koch Institute for Integrative Cancer Research at MIT
Journal
Cancer Cell
Publisher
Elsevier
Citation
Ianari, Alessandra, Tiziana Natale, Eliezer Calo, Elisabetta Ferretti, Edoardo Alesse, Isabella Screpanti, Kevin Haigis, Alberto Gulino, and Jacqueline A. Lees. “Proapoptotic Function of the Retinoblastoma Tumor Suppressor Protein.” Cancer Cell 15, no. 3 (March 2009): 184-194. Copyright © 2009 Elsevier Inc.
Version: Final published version
ISSN
15356108

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