Expression and localization of cyclin-dependent kinase 5 in apoptotic human glioma cells

Cyclin-dependent kinase 5 (Cdk5), a member of the cyclin-dependent kinase f amily, is expressed predominately in mature neurons and is implicated in ne urite extension, neuronal migration, and neuronal differentiation. Cdk5 pro tein expression also has been associated with apoptosis in a number of nonn euronal model systems. In normal brain, substrates for Cdk5 include neurofi lament and tau proteins. Because human tumors of glial origin can express n euronal proteins, we examined whether Cdk5 and its activator protein, P35, are present in early passage human glioblastoma multiforme (GBM) cells line s and primary tumor specimens. Here we report the expression of Cdk5 and an "active" proteolytic form of P35 in human GEM cells and demonstrate kinase activity of the holoenzyme. We also show that Cdk5 kinase activity and exp ression of its activator protein, P35, is increased in the human GEM cell l ine M053J after exposure to ionizing radiation and that P35 is localized wi thin M053J cells undergoing apoptosis. These results suggest a possible rol e for Cdk5 in mediating apoptosis in human GEM cells.