© 2001 by Society
© 2001 by the Society forNeuro-Oncology
Expression and localization of cyclin-dependent kinase 5 in apoptotichuman glioma cells
Cross Cancer Institute, Edmonton, Alberta T6G 1Z2(A.C., S.U., E.Y., G.B., J.A.-T.); and the Departmentsof Laboratory Medicine and Pathology (C.H.) and Oncology (A.C., E.Y., J.A.-T.), University of Alberta,Edmonton, Alberta, Canada T6G 2E1
3 Address correspondence and reprint requests to Joan Allalunis-Turner,Experimental Oncology, Cross Cancer Institute, 11560 University Ave.,Edmonton, AB, Canada T6G 1Z2.
Cyclin-dependent kinase 5 (Cdk5), a member of the cyclin-dependent kinasefamily, is expressed predominately in mature neurons and is implicated inneurite extension, neuronal migration, and neuronal differentiation. Cdk5protein expression also has been associated with apoptosis in a number ofnonneuronal model systems. In normal brain, substrates for Cdk5 includeneurofilament and tau proteins. Because human tumors of glial origin canexpress neuronal proteins, we examined whether Cdk5 and its activator protein,P35, are present in early passage human glioblastoma multiforme (GBM) cellslines and primary tumor specimens. Here we report the expression of Cdk5 andan "active" proteolytic form of P35 in human GBM cells anddemonstrate kinase activity of the holoenzyme. We also show that Cdk5 kinaseactivity and expression of its activator protein, P35, is increased in thehuman GBM cell line M059J after exposure to ionizing radiation and that P35 islocalized within M059J cells undergoing apoptosis. These results suggest apossible role for Cdk5 in mediating apoptosis in human GBM cells.
Received June 20, 2000; Accepted November 15, 2000
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