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Publication : Proapoptotic function of the retinoblastoma tumor suppressor protein.

First Author  Ianari A Year  2009
Journal  Cancer Cell Volume  15
Issue  3 Pages  184-94
PubMed ID  19249677 Mgi Jnum  J:145939
Mgi Id  MGI:3836347 Doi  10.1016/j.ccr.2009.01.026
Citation  Ianari A, et al. (2009) Proapoptotic function of the retinoblastoma tumor suppressor protein. Cancer Cell 15(3):184-94
abstractText  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.
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