Degradation of p35, a neuron-specific activator of CDK5, was studied in rat cortical neurons in primary culture. Treatment of cultured neurons with cyclohexamide induced the rapid disappearance of p35 accompanied by parallel inactivation of the kinase activity of CDK5. The disappearance of p35 was blocked with proteasome inhibitors benzyloxycarbonyl-leucyl-leucyl-leucinal and lactacystin, indicating the involvement of proteasome. The degradation of p35 was induced with okadaic acid in the presence of ATP in neuron extracts. The degradation of p35 by proteasome in cultured neurons was stimulated by okadaic acid in the absence of cyclohexamide. These results indicate that p35 is degraded by proteasome in a phosphorylation-dependent manner in neurons.
Copyright 1998 Academic Press.