Hzf Determines cell survival upon genotoxic stress by modulating p53 transactivation

Cell. 2007 Aug 24;130(4):624-37. doi: 10.1016/j.cell.2007.06.013.


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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


  • Proteins
  • RNA, Small Interfering
  • Recombinant Proteins
  • Tumor Suppressor Protein p53
  • Zfp385 protein, mouse
  • Glutathione Transferase