¹Quark Biotech Inc., 10265 Carnegi Ave, Cleveland, Ohio, OH 44106, USA

²Department of Molecular Biology, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Ave, Ohio, OH 44195, USA

Correspondence to: E Feinstein, Quark Biotech Inc./QBI Enterprises, Ltd., Weizmann Science Park, POB 4071, Ness Ziona, 70400 Israel; E-mail: elenaf@qbi.co.il or PM Chrumakov, Department of Molecular Biology, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Ave, OH 44195, USA; E-mail: chumakp@ccf.org

^aThese authors have contributed equally to this work

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 (- 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 H₂O₂. Thus, Hi95 gene seems to be involved in complex regulation of cell viability in response to different stress conditions.

Oncogene (2002) 21, 6017-6031. doi:10.1038/sj.onc.1205877

hypoxia; p53-responsive gene; cell viability; stress response