期刊
CELL
卷 130, 期 4, 页码 624-637出版社
CELL PRESS
DOI: 10.1016/j.cell.2007.06.013
关键词
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资金
- NCI NIH HHS [R01 CA078356, 1R01 CA097216, P01 CA80058, R01 CA078356-10, 2R01 CA078356, R01 CA085214, 2R01 CA085681, 2R01 CA085214, R01 CA085681, R01 CA097216, R01 CA097216-06, P01 CA080058, R01 CA085681-08] Funding Source: Medline
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.
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