Proapoptotic Function of the Retinoblastoma Tumor Suppressor Protein
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Lees_Proapoptotic function.pdf
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Author(s)
Ianari, Alessandra
Natale, Tiziana
Calo, Eliezer
Ferretti, Elisabetta
Alesse, Edoardo
Screpanti, Isabella
Haigis, Kevin M.
Gulino, Alberto
Lees, Jacqueline
Date Issued
March 2009
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
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1016/j.ccr.2009.01.026
