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c-Abl tyrosine kinase regulates the human Rad9 checkpoint protein in response to DNA damage.

The ubiquitously expressed c-Abl tyrosine kinase is activated in the apoptotic response of cells to DNA damage. The mechanisms by which c-Abl signals the induction of apoptosis are not understood. Here we show that c-Abl binds constitutively to the mammalian homolog of the Schizosaccharomyces pombe Rad9 cell cycle checkpoint protein. The SH3 domain of c-Abl interacts directly with the C-terminal region of Rad9. c-Abl phosphorylates the Rad9 Bcl-2 homology 3 domain (Tyr-28) in vitro and in cells exposed to DNA-damaging agents. The results also demonstrate that c-Abl-mediated phosphorylation of Rad9 induces binding of Rad9 to the antiapototic Bcl-x(L) protein. The regulation of Rad9 by c-Abl in the DNA damage response is further supported by the demonstration that the interaction between c-Abl and Rad9 contributes to DNA damage-induced apoptosis. These findings indicate that Rad9 is regulated by a c-Abl-dependent mechanism in the apoptotic response to genotoxic stress.

Pubmed ID: 11971963


  • Yoshida K
  • Komatsu K
  • Wang HG
  • Kufe D


Molecular and cellular biology

Publication Data

May 24, 2002

Associated Grants

  • Agency: NCI NIH HHS, Id: CA29431
  • Agency: NCI NIH HHS, Id: CA55241

Mesh Terms

  • Apoptosis
  • Cell Cycle Proteins
  • Cell Line
  • DNA Damage
  • Flow Cytometry
  • Humans
  • Phosphorylation
  • Protein Binding
  • Proto-Oncogene Proteins c-abl
  • Proto-Oncogene Proteins c-bcl-2
  • Recombinant Fusion Proteins
  • Transfection
  • Tyrosine
  • bcl-X Protein