p53 directly transactivates Delta133p53alpha, regulating cell fate outcome in response to DNA damage.
Summary of "p53 directly transactivates Delta133p53alpha, 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 Delta133p53alpha, which can modulate p53 transcriptional activity and apoptosis. In this study, we aimed to investigate the regulation of Delta133p53alpha 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 Delta133p53alpha protein expression. The induced Delta133p53alpha then inhibits p53-dependent apoptosis and G1 arrest without inhibiting p53-dependent G2 arrest. Therefore, endogenous Delta133p53alpha does not exclusively function in a dominant-negative manner toward p53, but differentially regulates cell cycle arrest and apoptosis.Cell Death and Differentiation advance online publication, 6 August 2010; doi:10.1038/cdd.2010.91.
Centre for Oncology and Molecular Medicine, Inserm-European Associated Laboratory U858, University of Dundee, College of Medicine, Dundee, DD1 9SY, UK.
This article was published in the following journal.
Name: Cell death and differentiation
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20689555
- DOI: http://dx.doi.org/10.1038/cdd.2010.91
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