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 death and found that the expression of cyclin-dependent kinase 5 (Cdk5) is associated with apoptotic cell death in both adult and embryonic tissues. 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 to Cdk5 as this association is not found with the other Cdks (Cdk 1-8) and cell death. The differential increase in Cdk5 expression is at the level of protein only, and no differences can be detected at the level of mRNA Using both limbs of mutant mice detective in the pattern of interdigital cell death 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 found p35 to be expressed in the dying cells as well. Similar to Cdk5, there is also no specific differential expression of the p35 mRNA in dying cells. Our results suggest a role for Cdk5 and p35 proteins in cell death. This protein complex may function in the rearrangement of the cytoskeleton during apoptosis.