p35 is a neural-specific regulatory subunit of cyclin-dependent kinase 5.
Cyclin-dependent kinase 5 (Cdk5) was originally isolated through its structural homology to human Cdc2, a key regulator of cell-cycle progression. In tissue samples from adult mice, Cdk5 protein is found at the highest level in brain, at an intermediate level in testis, and at low or undetectable levels in all other tissues, but brain is the only tissue that shows Cdk5 histone H1 kinase activity. No equivalent kinase activity has been found in tissue culture cell lines despite high levels of Cdk5. This raised the possibility that a Cdk5 regulatory subunit was responsible for the activation of Cdk5 in brain. Here we describe the cloning and characterization of a regulatory subunit for 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 represents a new type of regulatory subunit for cyclin-dependent kinase activity.
Tsai
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Massachusetts General Hospital Cancer Center, Charlestown 02129.
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002478:Cells, Cultured; D002490:Central Nervous System / Q000196:embryology / Q000201:enzymology; D002540:Cerebral Cortex / Q000166:cytology / Q000201:enzymology; D003001:Cloning, Molecular; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases; D004247:DNA; D004622:Embryo, Mammalian; D004789:Enzyme Activation; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000201:enzymology*; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured
D009419:Nerve Tissue Proteins; C089495:neuronal Cdk5 activator (p25-p35); D004247:DNA; D051360:Cyclin-Dependent Kinase 5; D017346:Protein Serine-Threonine Kinases; C495905:CDK5 protein, human; C495906:Cdk5 protein, mouse; D018844:Cyclin-Dependent Kinases