Pro-apoptotic effect of the c-Abl tyrosine kinase in the cellular response to 1-beta-D-arabinofuranosylcytosine.
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.
Huang
Y
Y
Division of Cancer Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Yuan
Z M
ZM
Ishiko
T
T
Nakada
S
S
Utsugisawa
T
T
Kato
T
T
Kharbanda
S
S
Kufe
D W
DW
D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D003561:Cytarabine / Q000494:pharmacology*; D004249:DNA Damage; D004261:DNA Replication / Q000187:drug effects; D006801:Humans; D016374:Oncogene Proteins v-abl / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*
D016374:Oncogene Proteins v-abl; D003561:Cytarabine; D011505:Protein-Tyrosine Kinases