The structural perspective on CDK5.
Cyclin-dependent kinase 5 (CDK5) plays an essential role in the development of the central nervous system during mammalian embryogenesis. In the adult, CDK5 is required for the maintenance of neuronal architecture. Its deregulation has profound cytotoxic effects and has been implicated in the development of neurodegenerative diseases such as Alzheimer's disease and amyotrophic lateral sclerosis. In this review, we concentrate on the regulation of CDK5 activity, privileging a structural perspective based on a decade of structural analyses of different members of the CDK family, including CDK2 and CDK5. We review the activation mechanism of CDK5 and discuss its differences and similarities with that of CDK2 and of the other members of the CDK family.
Mapelli
Marina
M
Structural Biology Unit, Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.
Musacchio
Andrea
A
D000818:Animals; D042846:CDC2-CDC28 Kinases / Q000737:chemistry / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000737:chemistry* / Q000378:metabolism; D004789:Enzyme Activation; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011485:Protein Binding; D013329:Structure-Activity Relationship
C108298:Cdk5 activator p39; D009419:Nerve Tissue Proteins; C089495:neuronal Cdk5 activator (p25-p35); D051360:Cyclin-Dependent Kinase 5; D042846:CDC2-CDC28 Kinases; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases