P35 IS A NEURAL-SPECIFIC REGULATORY SUBUNIT OF CYCLIN-DEPENDENT KINASE-5

CYCLIN-dependent kinase 5 (Cdk5) was originally isolated through its s tructural homology to human Cdc2(1), a key regulator of cell-cycle pro gression(2-6). In tissue samples from adult mice, Cdk5 protein is foun d at the highest level in brain, at an intermediate level in testis, a nd at low or undetectable levels in all other tissues, but brain is th e only tissue that shows Cdk5 histone H1 kinase activity(7). No equiva lent kinase activity has been found in tissue culture cell lines despi te high levels of Cdk5 This raised the possibility that a Cdk5 regulat ory subunit was responsible for the activation of Cdk5 in brain. Here we describe the cloning and characterization of a regulatory subunit f or Cdk5 known as p35. p35 displays a neuronal cell-specific pattern of expression, it associates physically with Cdk5 in vivo and activates the Cdk5 kinase. p35 differs from the mammalian cyclins and thus repre sents a new type of regulatory subunit for cyclin-dependent kinase act ivity.