Bnip3L is induced by p53 under hypoxia, and its knockdown promotes tumor growth

University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Cancer Cell (Impact Factor: 23.89). 01/2005; 6(6):597-609. DOI: 10.1016/j.ccr.2004.10.012
Source: PubMed

ABSTRACT p53-dependent apoptosis is a major determinant of its tumor suppressor activity and can be triggered by hypoxia. No p53 target is known to be induced by p53 or to mediate p53-dependent apoptosis during hypoxia. We report that p53 can directly upregulate expression of Bnip3L, a cell death inducer. During hypoxia, Bnip3L is highly induced in wild-type p53-expressing cells, in part due to increased recruitment of p53 and CBP to Bnip3L. Apoptosis is reduced in hypoxia-exposed cells with functional p53 following Bnip3L knockdown. In vivo, Bnip3L knockdown promotes tumorigenicity of wild-type versus mutant p53-expressing tumors. Thus, Bnip3L, capable of attenuating tumorigenicity, mediates p53-dependent apoptosis under hypoxia, which provides a novel understanding of p53 in tumor suppression.


Available from: Eric J Bernhard, Jun 03, 2015
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