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p73 is regulated by tyrosine kinase c-Abl in the apoptotic response to DNA damage

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Listed:
  • Zhi-Min Yuan

    (Harvard School of Public Health
    Dana-Farber Cancer Institute, Harvard Medical School)

  • Hisashi Shioya

    (Dana-Farber Cancer Institute, Harvard Medical School)

  • Takatoshi Ishiko

    (Dana-Farber Cancer Institute, Harvard Medical School)

  • Xiangao Sun

    (Dana-Farber Cancer Institute, Harvard Medical School)

  • Jijie Gu

    (Harvard School of Public Health
    Dana-Farber Cancer Institute, Harvard Medical School)

  • YinYin Huang

    (Dana-Farber Cancer Institute, Harvard Medical School)

  • Hua Lu

    (Oregon Health Science University)

  • Surender Kharbanda

    (Dana-Farber Cancer Institute, Harvard Medical School)

  • Ralph Weichselbaum

    (University of Chicago)

  • Donald Kufe

    (Harvard School of Public Health
    Dana-Farber Cancer Institute, Harvard Medical School)

Abstract

The protein p73 is a structural and functional homologue of the p53 tumour-suppressor protein but, unlike p53, it is not induced in response to DNA damage1,2. The tyrosine kinase c-Abl is activated by certain DNA-damaging agents3 and contributes tothe induction of programmed cell death (apoptosis) by p53-dependent and p53-independent mechanisms4. Here we show that c-Abl binds to p73 in cells, interacting through its SH3 domain with the carboxy-terminal homo-oligomerization domain of p73. c-Abl phosphorylates p73 on a tyrosine residue at position 99 both in vitro and in cells that have been exposed to ionizing radiation. Our results show that c-Abl stimulates p73-mediated transactivation and apoptosis. This regulation of p73 by c-Abl in response to DNA damage is also demonstrated by a failure of ionizing-radiation-induced apoptosis after disruption of the c-Abl–p73 interaction. These findings show that p73 is regulated by a c-Abl-dependent mechanism and that p73 participates in the apoptotic response to DNA damage.

Suggested Citation

  • Zhi-Min Yuan & Hisashi Shioya & Takatoshi Ishiko & Xiangao Sun & Jijie Gu & YinYin Huang & Hua Lu & Surender Kharbanda & Ralph Weichselbaum & Donald Kufe, 1999. "p73 is regulated by tyrosine kinase c-Abl in the apoptotic response to DNA damage," Nature, Nature, vol. 399(6738), pages 814-817, June.
    • Handle: RePEc:nat:nature:v:399:y:1999:i:6738:d:10.1038_21704
    DOI: 10.1038/21704
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