TableEdit

Das, S, Raj, L, Zhao, B, Kimura, Y, Bernstein, A, Aaronson, SA and Lee, SW (2007) Hzf Determines cell survival upon genotoxic stress by modulating p53 transactivation. Cell 130:624-37

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.

PubMed PMC2779720 Online version:10.1016/j.cell.2007.06.013

Animals; Apoptosis/genetics; Apoptosis/radiation effects; Cell Culture Techniques; Cell Line, Tumor; Cell Survival; DNA Damage; Feedback, Physiological; Female; Gamma Rays; Glutathione Transferase/metabolism; HCT116 Cells; Humans; Immunohistochemistry; Male; Mice; Models, Biological; Osteosarcoma/pathology; Prostatic Neoplasms/pathology; Proteins/genetics; Proteins/metabolism; RNA, Small Interfering; Recombinant Proteins/metabolism; Transcriptional Activation; Tumor Suppressor Protein p53/genetics; Tumor Suppressor Protein p53/metabolism; Two-Hybrid System Techniques; Whole-Body Irradiation