title: c-Abl is required for staurosporine-induced caspase activity.
abstract: Caspases are the intracellular molecular machinery responsible for apoptotic cell death. The regulation of these critical proteolytic enzymes is known to occur on multiple levels. While their expression as inactive precursors exhibits a primary level of control, other types of regulation such as post-translational modifications also play a role. Nuclear c-Abl, a nonreceptor tyrosine kinase, plays a role in the regulation of apoptosis in response to DNA damage. The function of cytoplasmic c-Abl in cell death is not fully understood. Here, we report c-Abl dependent caspase-3 and caspase-8 activity in response to staurosporine. Despite the presence and apparent activation of the mitochondrial-dependent apoptotic pathway and cellular demise, we find no caspase-3 activity in cells lacking the Abl gene (Abl(-/-)). These findings demonstrate a novel tyrosine kinase dependent regulation of caspase-mediated cell death.
authors.affiliation: Department of Pharmacology, MS 318, University of Nevada School of Medicine, Reno 89557, USA.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Oxhorn
authors.forename: Amy R
authors.initials: AR
authors.lastname: Sanguinetti
authors.forename: Cynthia Corley
authors.initials: CC
authors.lastname: Mastick
authors.forename: Iain L O
authors.initials: IL
authors.lastname: Buxton
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D053148:Caspase 3; D053181:Caspase 8; D020169:Caspases / Q000378:metabolism*; D002460:Cell Line; D003124:Colorimetry; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D018345:Mice, Knockout; D016315:Proto-Oncogene Proteins c-abl / Q000502:physiology*; D019311:Staurosporine / Q000494:pharmacology*
chemical_list: D045304:Cytochromes c; D016315:Proto-Oncogene Proteins c-abl; C505409:Casp3 protein, mouse; C505526:Casp8 protein, mouse; D053148:Caspase 3; D053181:Caspase 8; D020169:Caspases; D019311:Staurosporine