title: Biological functions of CDK5 and potential CDK5 targeted clinical treatments.
abstract: Cyclin dependent kinases are proline-directed serine/threonine protein kinases that are traditionally activated upon association with a regulatory subunit. For most CDKs, activation by a cyclin occurs through association and phosphorylation of the CDK's T-loop. CDK5 is unusual because it is not typically activated upon binding with a cyclin and does not require T-loop phosphorylation for activation, even though it has high amino acid sequence homology with other CDKs. While it was previously thought that CDK5 only interacted with p35 or p39 and their cleaved counterparts, Recent evidence suggests that CDK5 can interact with certain cylins, amongst other proteins, which modulate CDK5 activity levels. This review discusses recent findings of molecular interactions that regulate CDK5 activity and CDK5 associated pathways that are implicated in various diseases. Also covered herein is the growing body of evidence for CDK5 in contributing to the onset and progression of tumorigenesis.
authors.affiliation: Departments of Cancer Biology, Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Alison
authors.initials: A
authors.lastname: Shupp
authors.affiliation: Pennsylvania Cancer and Regenerative Medicine Research Center, Baruch S Blumberg Institute, Doylestown, PA, USA.
authors.forename: Mathew C
authors.initials: MC
authors.lastname: Casimiro
authors.affiliation: Pennsylvania Cancer and Regenerative Medicine Research Center, Baruch S Blumberg Institute, Doylestown, PA, USA.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Pestell
mesh_terms: D000818:Animals; D055162:Biocatalysis / Q000187:drug effects; D051360:Cyclin-Dependent Kinase 5 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016213:Cyclins; D047428:Protein Kinase Inhibitors; D051360:Cyclin-Dependent Kinase 5; C495905:CDK5 protein, human
keywords: CDK5; cancer