| First Author | Das S | Year | 2007 |
| Journal | Cell | Volume | 130 |
| Issue | 4 | Pages | 624-37 |
| PubMed ID | 17719541 | Mgi Jnum | J:200408 |
| Mgi Id | MGI:5508602 | Doi | 10.1016/j.cell.2007.06.013 |
| Citation | Das S, et al. (2007) Hzf Determines cell survival upon genotoxic stress by modulating p53 transactivation. Cell 130(4):624-37 |
| abstractText | 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. |
