Okadaic acid-stimulated degradation of p35, an activator of CDK5, by proteasome in cultured neurons

Degradation of p35, a neuron-specific activator of CDK5, was studied in rat cortical neurons in primary culture. Treatment of cultured neurons with cy clohexamide induced the rapid disappearance of p35 accompanied by parallel inactivation of the kinase activity of CDK5, The disappearance of p35 was b locked 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 extra cts. The degradation of p35 by proteasome in cultured neurons was stimulate d by okadaic acid in the absence of cyclohexamide. These results indicate t hat p35 is degraded by proteasome in a phosphorylation-dependent manner in neurons. (C) 1998 Academic Press.