Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

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

Oncogene volume 21, pages 6017–6031 (2002)Cite this article

Abstract

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 (γ- 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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9

Similar content being viewed by others

References

  • Alexandrova A, Ivanov A, Chumakov P, Kopnin B, Vasiliev J . 2000 Oncogene 19: 5826–5830

  • An WG, Kanekal M, Simon MC, Maltepe E, Blagosklonny MV, Neckers LM . 1998 Nature 392: 405–408

  • Batchvarova N, Wang XZ, Ron D . 1995 EMBO J. 14: 4654–4661

  • Bischoff FZ, Strong LC, Yim SO, Pratt DR, Siciliano MJ, Giovanella BC, Tainsky MA . 1991 Oncogene 6: 183–186

  • Bruick RK . 2000 Proc. Natl. Acad. Sci. USA 97: 9082–9087

  • Bunn HF, Poyton RO . 1996 Physiol. Rev. 76: 839–885

  • Carmeliet P, Dor Y, Herbert JM, Fukumura D, Brusselmans K, Dewerchin M, Neeman M, Bono F, Abramovitch R, Maxwell P, Koch CJ, Ratcliffe P, Moons L, Jain RK, Collen D, Keshert E, Keshet E . 1998 Nature 394: 485–490

  • Chen C, Okayama H . 1987 Mol. Cell Biol. 7: 2745–2752

  • Dini MM, Jafari K, Faiferman I . 1980 Obstet. Gynecol. 55: 728–731

  • Dong Z, Venkatachalam MA, Wang J, Patel Y, Saikumar P, Semenza GL, Force T, Nishiyama J . 2001 J. Biol. Chem. 276: 18702–18709

  • Faerman A, Shani M . 1997 Methods Cell Biol. 52: 373–403

  • Feldser D, Agani F, Iyer NV, Pak B, Ferreira G, Semenza GL . 1999 Cancer Res. 59: 3915–3918

  • Fornace Jr AJ . 1992 Annu. Rev. Genet. 26: 507–526

  • Fornace Jr AJ, Jackman J, Hollander MC, Hoffman-Liebermann B, Liebermann DA . 1992 Ann NY Acad Sci. 663: 139–153

  • Fornace Jr AJ, Nebert DW, Hollander MC, Luethy JD, Papathanasiou M, Fargnoli J, Holbrook NJ . 1989 Mol. Cell Biol. 9: 4196–4203

  • Gossen M, Bujard H . 1992 Proc. Natl. Acad. Sci. USA 89: 5547–5551

  • Graeber TG, Osmanian C, Jacks T, Housman DE, Koch CJ, Lowe SW, Giaccia AJ . 1996 Nature 379: 88–91

  • Graeber TG, Peterson JF, Tsai M, Monica K, Fornace Jr AJ, Giaccia AJ . 1994 Mol. Cell Biol. 14: 6264–6277

  • Graham FL, Smiley J, Russell WC, Nairn R . 1977 J. Gen. Virol. 36: 59–74

  • Guillemin K, Krasnow MA . 1997 Cell 89: 9–12

  • Hikasa H, Taira M . 2001 Mech. Dev. 100: 309–312

  • Jones PA, Laug WE, Benedict WF . 1975 Cell 6: 245–252

  • Kataoka Y, Murley JS, Patel R, Grdina DJ . 2000 Int. J. Radiat. Biol. 76: 633–639

  • Komarova EA, Christov K, Faerman AI, Gudkov AV . 2000 Oncogene 19: 3791–3798

  • Leker RR, Teichner A, Ovadia H, Keshet E, Reinherz E, Ben-Hur T . 2001 Brain Res. 909: 1–7

  • Liu Y, Cox SR, Morita T, Kourembanas S . 1995 Circ. Res. 77: 638–643

  • Long X, Boluyt MO, Hipolito ML, Lundberg MS, Zheng JS, O'Neill L, Cirielli C, Lakatta EG, Crow MT . 1997 J. Clin. Oncol. Invest. 99: 2635–2643

  • McCullough KD, Martindale JL, Klotz LO, Aw TY, Holbrook NJ . 2001 Mol. Cell Biol. 21: 1249–1259

  • Pinkerton H, Rana MW . 1976 Proc. Soc. Exp. Biol. Med. 151: 532–534

  • Price BD, Calderwood SK . 1992 Cancer Res. 52: 3814–3817

  • Sambrook J, Fritsch E, Maniatis T . 1989 Cold Spring Harbor Laboratory Press

  • Schena M, Shalon D, Heller R, Chai A, Brown PO, Davis RW . 1996 Proc. Natl. Acad. Sci. USA 93: 10614–10619

  • Semenza GL . 1999 Annu. Rev. Cell Dev. Biol. 15: 551–578

  • Semenza GL . 2000 Genes Dev. 14: 1983–1991

  • Sheikh MS, Hollander MC, Fornace Jr AJ . 2000 Biochem. Pharmacol. 59: 43–45

  • Shoshani T, Faerman A, Zelin E, Tena T, Gorodin S, Moshel Y, Puzis R, Fomin M, Budanov A, Chajut A, Kalinski H, Rozen A, Mor O, Keshet E, Leshkowitz D, Einat P, Skaliter R, Faerman E . 2002 Mol. Cell Biol. 22: 2283–2293

  • Smith ML, Fornace Jr AJ . 1996 Mutat. Res. 340: 109–124

  • Sowter HM, Ratcliffe PJ, Watson P, Greenberg AH, Harris AL . 2001 Cancer Res. 61: 6669–6673

  • Stratmann R, Krieg M, Haas R, Plate KH . 1997 J. Neuropathol. Exp. Neurol. 56: 1242–1252

  • Takekawa M, Saito H . 1998 Cell 95: 521–530

  • Vande Velde C, Cizeau J, Dubik D, Alimonti J, Brown T, Israels S, Hakem R, Greenberg AH . 2000 Mol. Cell Biol. 20: 5454–5468

  • Velasco-Miguel S, Buckbinder L, Jean P, Gelbert LRT, Laidlaw J, Seizinger B, Kley N . 1999 Oncogene 18: 127–137

  • Wallach D . 1984 J. Immunol. 132: 2464–2469

  • Westley B, Rochefort H . 1979 Biochem. Biophys. Res. Commun. 90: 410–416

  • Whitehead RH, Macrae FA, St John DJ, Ma J . 1985 J. Natl. Cancer Inst. 74: 759–765

  • Zhan Q, Fan S, Smith ML, Bae I, Yu K, Alamo Jr I, O'Connor PM, Fornace Jr AJ . 1996 DNA Cell Biol. 15: 805–815

  • Zhang W, Hoffman B, Liebermann DA . 2001 Int. J. Oncol. 18: 749–757

Download references

Acknowledgements

We are grateful to H Ovadia and R Lecker for performance of the MCAO model in rats, and to A Rosenbluh for the reading and correction of the manuscript. We also want to thank E Berent, L Novak, A Bar-On, Y Moshel and N Alima for excellent technical assistance and Mitsubishi-Tokyo Pharmaceuticals Inc. for support. This work was supported by grants of Quark Biotech Inc to PM Chumakov and AV Gudkov.

Author information

Author notes

  1. Andrei V Budanov and Tzipora Shoshani: These authors have contributed equally to this work

Authors and Affiliations

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

    Tzipora Shoshani, Alexander Faerman, Elena Zelin, Iris Kamer, Hagar Kalinski, Svetlana Gorodin, Alla Fishman, Ayelet Chajut, Paz Einat, Rami Skaliter & Elena Feinstein

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

    Andrei V Budanov, Andrei V Gudkov & Peter M Chrumakov

Authors
  1. Andrei V Budanov
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tzipora Shoshani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alexander Faerman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Elena Zelin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Iris Kamer
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hagar Kalinski
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Svetlana Gorodin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Alla Fishman
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ayelet Chajut
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Paz Einat
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Rami Skaliter
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Andrei V Gudkov
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Peter M Chrumakov
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Elena Feinstein
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Peter M Chrumakov or Elena Feinstein.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Budanov, A., Shoshani, T., Faerman, A. et al. Identification of a novel stress-responsive gene Hi95 involved in regulation of cell viability. Oncogene 21, 6017–6031 (2002). https://doi.org/10.1038/sj.onc.1205877

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1205877

Keywords

This article is cited by

Search

Advanced search

Quick links