p53 directly transactivates Delta 133p53 alpha, regulating cell fate outcome in response to DNA damage

We have previously reported that the human p53 gene encodes at least nine different p53 isoforms, including Delta 133p53 alpha, which can modulate p53 transcriptional activity and apoptosis. In this study, we aimed to investigate the regulation of Delta 133p53 alpha isoform expression and its physiological role in modulating cell cycle arrest and apoptosis. We report here that in response to a low dose of doxorubicin (which induces cell cycle arrest without promoting apoptosis), p53 directly transactivates the human p53 internal promoter, inducing Delta 133p53 alpha protein expression. The induced Delta 133p53 alpha then inhibits p53-dependent apoptosis and G1 arrest without inhibiting p53-dependent G2 arrest. Therefore, endogenous Delta 133p53 alpha does not exclusively function in a dominant-negative manner toward p53, but differentially regulates cell cycle arrest and apoptosis. Cell Death and Differentiation (2011) 18, 248-258; doi: 10.1038/cdd.2010.91; published online 6 August 2010