Title: Hzf Determines cell survival upon genotoxic stress by modulating p53 transactivation. | Journal: Cell. 2007 Aug;130(4):624-37 | Authors: Das S, Raj L, Zhao B, Kimura Y, Bernstein A, Aaronson SA, Lee SW. | Abstract: A critical unresolved issue about the genotoxic stress response is how the resulting activation of the p53 tumor suppressor can lead either to cell-cycle arrest and DNA repair or to apoptosis. We show here that hematopoietic zinc finger (Hzf), a zinc-finger-containing p53 target gene, modulates p53 transactivation functions in an autoregulatory feedback loop. Hzf is induced by p53 and binds to its DNA-binding domain, resulting in preferential transactivation of proarrest p53 target genes over its proapoptotic target genes. Thus, p53 activation results in cell-cycle arrest in Hzf wild-type MEFs, while in Hzf(-/-) MEFs, apoptosis is induced. Exposure of Hzf null mice to ionizing radiation resulted in enhanced apoptosis in several organs, as compared to in wild-type mice. These findings provide novel insights into the regulation of p53 transactivation function and suggest that Hzf functions as a key player in regulating cell fate decisions in response to genotoxic stress. | See full PubMed entry: http://www.ncbi.nlm.nih.gov/pubmed/17719541 |
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