Identification of a novel stress-responsive gene Hi95 involved in regulation of cell viability.
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.
Department of Molecular Biology, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Ave, Ohio, OH 44195, USA.
Andrei V
AV
Budanov
Tzipora
T
Shoshani
Alexander
A
Faerman
Elena
E
Zelin
Iris
I
Kamer
Hagar
H
Kalinski
Svetlana
S
Gorodin
Alla
A
Fishman
Ayelet
A
Chajut
Paz
P
Einat
Rami
R
Skaliter
Andrei V
AV
Gudkov
Peter M
PM
Chumakov
Elena
E
Feinstein
D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002455:Cell Division; D002470:Cell Survival; D003001:Cloning, Molecular; D017931:DNA Primers / Q000737:chemistry; D004317:Doxorubicin / Q000494:pharmacology; D005910:Glioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D000860:Hypoxia / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D000084622:Sestrins
D000970:Antineoplastic Agents; D017931:DNA Primers; D004317:Doxorubicin; D006861:Hydrogen Peroxide; D009687:Nuclear Proteins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; C465397:Hi95 protein, mouse; C465398:SESN2 protein, human; D000084622:Sestrins