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Interaction of c-Abl and p73alpha and their collaboration to induce apoptosis

R Agami1, G Blandino, M Oren

  • 1Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel.

Nature
|July 3, 1999
PubMed

Insights

The study reveals that the tumor suppressor p73alpha requires the kinase c-Abl for its apoptotic function. DNA damage activates this p73 and c-Abl pro-apoptotic signaling pathway.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • c-Abl (a non-receptor tyrosine kinase) is activated by DNA damage, leading to cell cycle arrest or apoptosis.
  • p73, a p53 family tumor suppressor, also induces apoptosis.

Purpose of the Study:

  • To investigate the relationship between p73 and c-Abl in apoptosis.
  • To elucidate the mechanism of p73-mediated apoptosis.

Main Methods:

  • Investigated the interaction between p73 and c-Abl.
  • Assessed the kinase activity of c-Abl on p73.
  • Utilized gamma-irradiation to induce DNA damage and observe phosphorylation changes.

Main Results:

  • p73alpha's apoptotic activity is dependent on functional, kinase-competent c-Abl.
  • p73 and c-Abl associate via a PxxP motif in p73 and the SH3 domain of c-Abl.
  • c-Abl phosphorylates p73, with increased phosphorylation observed after gamma-irradiation and in vivo.

Conclusions:

  • A novel pro-apoptotic signaling pathway involving p73 and c-Abl is defined.
  • c-Abl kinase activity is crucial for p73-mediated apoptosis.
  • Ionizing radiation enhances p73 phosphorylation by c-Abl.

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