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Publication : Differential contribution of Puma and Noxa in dual regulation of p53-mediated apoptotic pathways.

First Author  Shibue T Year  2006
Journal  EMBO J Volume  25
Issue  20 Pages  4952-62
PubMed ID  17024184 Mgi Jnum  J:119683
Mgi Id  MGI:3703129 Doi  10.1038/sj.emboj.7601359
Citation  Shibue T, et al. (2006) Differential contribution of Puma and Noxa in dual regulation of p53-mediated apoptotic pathways. EMBO J 25(20):4952-62
abstractText  The activation of tumor suppressor p53 induces apoptosis or cell cycle arrest depending on the state and type of cell, but it is not fully understood how these different responses are regulated. Here, we show that Puma and Noxa, the well-known p53-inducible proapoptotic members of the Bcl-2 family, differentially participate in dual pathways of the induction of apoptosis. In normal cells, Puma but not Noxa induces mitochondrial outer membrane permeabilization (MOMP), and this function is mediated in part by a pathway that involves calcium release from the endoplasmic reticulum (ER) and the subsequent caspase activation. However, upon E1A oncoprotein expression, cells also become susceptible to MOMP induction by Noxa, owing to their sensitization to the ER-independent pathway. These findings offer a new insight into differential cellular responses induced by p53, and may have therapeutic implications in cancer.
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