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

Kiyotsugu Yoshida, Kiyoshi Komatsu, Hong Gang Wang, Donald Kufe

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

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-xL 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.

Original languageEnglish (US)
Pages (from-to)3292-3300
Number of pages9
JournalMolecular and cellular biology
Volume22
Issue number10
DOIs
StatePublished - May 9 2002

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Protein-Tyrosine Kinases
DNA Damage
Apoptosis
Cell Cycle Proteins
src Homology Domains
Schizosaccharomyces
Cell Cycle Checkpoints
Phosphorylation
rad9 protein
DNA
Proteins

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Yoshida, Kiyotsugu ; Komatsu, Kiyoshi ; Wang, Hong Gang ; Kufe, Donald. / c-Abl tyrosine kinase regulates the human Rad9 checkpoint protein in response to DNA damage. In: Molecular and cellular biology. 2002 ; Vol. 22, No. 10. pp. 3292-3300.
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c-Abl tyrosine kinase regulates the human Rad9 checkpoint protein in response to DNA damage. / Yoshida, Kiyotsugu; Komatsu, Kiyoshi; Wang, Hong Gang; Kufe, Donald.

In: Molecular and cellular biology, Vol. 22, No. 10, 09.05.2002, p. 3292-3300.

Research output: Contribution to journalArticle

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