TY - JOUR T1 - Inhibition of c-Abl with STI571 Attenuates Stress-Activated Protein Kinase Activation and Apoptosis in the Cellular Response to 1-β-<span class="sc">d</span>-Arabinofuranosylcytosine JF - Molecular Pharmacology JO - Mol Pharmacol SP - 1489 LP - 1495 DO - 10.1124/mol.61.6.1489 VL - 61 IS - 6 AU - Deepak Raina AU - Neerad Mishra AU - Shailendra Kumar AU - Surender Kharbanda AU - Satya Saxena AU - Donald Kufe Y1 - 2002/06/01 UR - http://molpharm.aspetjournals.org/content/61/6/1489.abstract N2 - The response of myeloid leukemia cells to treatment with 1-β-d-arabinofuranosylcytosine (ara-C) includes activation of the c-Abl protein tyrosine kinase and the stress-activated protein kinase (SAPK). The present studies demonstrate that treatment of human U-937 leukemia cells with ara-C is associated with translocation of SAPK to mitochondria. STI571 (imatinib mesylate), an inhibitor of c-Abl, blocked both activation and mitochondrial targeting of SAPK in the ara-C response. In concert with these effects of STI571, similar findings were obtained in c-Abl–deficient cells. The results further show that STI571 inhibits ara-C–induced loss of mitochondrial transmembrane potential, caspase-3 activation, and apoptosis. These findings demonstrate that STI571 down-regulates c-Abl–mediated signals that target the mitochondria in the apoptotic response to ara-C. ER -