Pro-apoptotic effect of the c-Abl tyrosine kinase in the cellular response to 1-beta-D-arabinofuranosylcytosine

Oncogene. 1997 Oct 16;15(16):1947-52. doi: 10.1038/sj.onc.1201376.


Treatment of cells with the antimetabolite 1-beta-D-arabinofuranosylcytosine (ara-C) and other genotoxic agents is associated with activation of the c-Abl protein tyrosine kinase. The functional role of c-Abl in the response to DNA damage, however, remains unclear. The present studies demonstrate that cells expressing a dominant negative, kinase-inactive c-Abl (K-R) are resistant to killing by ara-C. The expression of c-Abl (K-R) blocked ara-C-induced apoptosis by a mechanism that is at least in part independent of the p53 tumor suppressor. Cells null for c-Abl also exhibited resistance to induction of apoptosis. These findings provide support for a pro-apoptotic function of c-Abl in the response to certain genotoxic drugs.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apoptosis / drug effects*
  • Cell Line
  • Cytarabine / pharmacology*
  • DNA Damage
  • DNA Replication / drug effects
  • Humans
  • Oncogene Proteins v-abl / metabolism*
  • Protein-Tyrosine Kinases / metabolism*


  • Oncogene Proteins v-abl
  • Cytarabine
  • Protein-Tyrosine Kinases