Identification of a novel stress-responsive gene Hi95 involved in regulation of cell viability

Oncogene. 2002 Sep 5;21(39):6017-31. doi: 10.1038/sj.onc.1205877.


cDNA microarray hybridization was used in an attempt to identify novel genes participating in cellular responses to prolonged hypoxia. One of the identified novel genes, designated Hi95 shared significant homology to a p53-regulated GADD family member PA26. In addition to its induction in response to prolonged hypoxia, the increased Hi95 transcription was observed following DNA damage or oxidative stress, but not following hyperthermia or serum starvation. Whereas induction of Hi95 by prolonged hypoxia or by oxidative stress is most likely p53-independent, its induction in response to DNA damaging treatments (gamma- or UV-irradiation, or doxorubicin) occurs in a p53-dependent manner. Overexpression of Hi95 full-length cDNA was found toxic for many types of cultured cells directly leading either to their apoptotic death or to sensitization to serum starvation and DNA damaging treatments. Unexpectedly, conditional overexpression of the Hi95 cDNA in MCF7-tet-off cells resulted in their protection against cell death induced by hypoxia/glucose deprivation or H(2)O(2). Thus, Hi95 gene seems to be involved in complex regulation of cell viability in response to different stress conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antineoplastic Agents / pharmacology
  • Base Sequence
  • Blotting, Northern
  • Blotting, Western
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Division
  • Cell Survival
  • Cloning, Molecular
  • DNA Primers / chemistry
  • Doxorubicin / pharmacology
  • Glioma / genetics*
  • Glioma / metabolism
  • Glioma / pathology
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Hypoxia / metabolism
  • In Situ Nick-End Labeling
  • Mice
  • Mice, Nude
  • Molecular Sequence Data
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger / metabolism
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism


  • Antineoplastic Agents
  • DNA Primers
  • Hi95 protein, mouse
  • Nuclear Proteins
  • RNA, Messenger
  • SESN2 protein, human
  • Tumor Suppressor Protein p53
  • Doxorubicin
  • Hydrogen Peroxide