Cyclin-dependent kinase-5 (Cdk5) is a serine/threonine kinase activated by its neuron-specific activator, p35, or its truncated form, p25. It has been proposed that the deregu-lation of Cdk5 activity by association with p25 in human brain tissue disrupts the neuronal cytoskeleton and may be involved in neurodegenerative diseases such as Alzheimer’s disease. In this study, we demonstrate that a short peptide (amino acid residues 154–279; Cdk5 inhibitory peptide; CIP), derived from p35, specifically inhibits Cdk5 activity in vitro and in HEK293 cells cotransfected with the peptide and Cdk5/p25, but had no effect on endogenous cdc2 kinase activity
