title: The suppression of drug-induced apoptosis by activation of v-ABL protein tyrosine kinase.
abstract: Cells with a temperature-sensitive mutant of the v-abl oncoprotein (IC.DP) were treated with the anticancer drugs melphalan or hydroxyurea. At the restrictive temperature for v-ABL protein tyrosine kinase activity, drug-treated IC.DP cells died by apoptosis. In contrast, apoptotic cell death induced by either drug was suppressed when v-ABL was active. However, melphalan-induced accumulation of cells in the S and G2-M phases of the cell cycle was unaffected by v-ABL activation. Moreover, the continuous presence of v-ABL activity was necessary to suppress apoptosis. This suggested that melphalan had interacted with DNA and that v-ABL activity prevented the coupling of drug-induced damage to the apoptotic pathway. IC.DP cells exhibited similar levels and subcellular localization of the BCL-2 protein irrespective of v-ABL activation status, thus v-ABL-mediated cell survival appeared to be independent of BCL-2.
authors.affiliation: Department of Biochemistry, University of Manchester Institute of Science and Technology, United Kingdom.
authors.forename: R S
authors.initials: RS
authors.lastname: Chapman
authors.forename: A D
authors.initials: AD
authors.lastname: Whetton
authors.forename: C
authors.initials: C
authors.lastname: Dive
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D004789:Enzyme Activation; D006918:Hydroxyurea / Q000494:pharmacology; D008558:Melphalan / Q000494:pharmacology; D051379:Mice; D016374:Oncogene Proteins v-abl / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000502:physiology*
chemical_list: D016374:Oncogene Proteins v-abl; D011505:Protein-Tyrosine Kinases; D008558:Melphalan; D006918:Hydroxyurea