ASSOCIATION OF CYCLIN-DEPENDENT KINASE-5 AND ITS ACTIVATOR P35 WITH APOPTOTIC CELL-DEATH

We have investigated the role of cyclin-dependent; kinases in cell dea th and found that the expression of cyclin-dependent kinase 5 (Cdk5) i s associated with apoptotic cell death in both adult and embryonic tis sues. By double labeling immunohistochemistry and confocal microscopy, we specifically associated the expression of Cdk5 to dying cells. The association of Cdks with cell death is unique io Cdk5 as this associa tion is not found with the other Cdks (Cdk 1-8) and cell death. The di fferential increase in Cdk5 expression is ai the level of protein only , and no differences can be detected al the level of mRNA. Using both limbs of mutant mice defective in the pattern of interdigital cell dea th? and limbs with increased interdigital cell death by retinoic acid treatment, we confirmed the specificity of Cdk5 protein expression in dying cells. To investigate the regulation of Cdk5 during cell death, we examined the expression of a regulatory protein of Cdk5, p35, and f ound p35 to be expressed in the dying cells as well. Similar io Cdk5, there is also no specific differential expression of the p35 mRNA in d ying cells. Our results suggest a role for Cdk5 and p35 proteins in ce ll death. This protein complex may function in the rearrangement of th e cytoskeleton during apoptosis. (C) 1997 Wiley-Liss, Inc.