Author/Authors :
Fei، نويسنده , , Peiwen and Wang، نويسنده , , Wenge and Kim، نويسنده , , Seok-hyun and Wang، نويسنده , , Shulin and Burns، نويسنده , , Timothy F. and Sax، نويسنده , , Joanna K. and Buzzai، نويسنده , , Monica and Dicker، نويسنده , , David T. and McKenna، نويسنده , , W.Gillies and Bernhard، نويسنده , , Eric J. and El-Deiry، نويسنده , , Wafik S. El-Deiry and Yigong Shi، نويسنده ,
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.
