Cdk5 and the non-catalytic arrest of the neuronal cell cycle.
Cyclin-dependent kinase 5 (Cdk5) is a nontraditional Cdk that is primarily active in postmitotic neurons. An important core function of Cdk5 involves regulating the migration and maturation of embryonic post-mitotic neurons. These developmental roles are dependent on its kinase activity. Initially, there was little evidence indicating a role for Cdk5 in normal cell cycle regulation. Recent data from our lab, however, suggest that Cdk5 plays a crucial role as a cell cycle suppressor in normal post-mitotic neurons and neuronal cell lines. It performs this foundation in a kinase independent manner. Cdk5 normally found in both nucleus and cytoplasm, but it exits the nucleus in neurons risk to death in an AD patient's brain. The shift in sub-cellular location is accompanied by cell cycle re-entry and neuronal death. This "new" function of Cdk5 raises cautions in the design of Cdk5-directed drugs for the therapy of neurodegenerative diseases.
Zhang
Jie
J
Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, New Jersey 08854-8082, USA.
Herrup
Karl
K
D000818:Animals; D002453:Cell Cycle; D051360:Cyclin-Dependent Kinase 5 / Q000502:physiology*; D006801:Humans; D019636:Neurodegenerative Diseases / Q000209:etiology; D009474:Neurons / Q000166:cytology* / Q000473:pathology
D051360:Cyclin-Dependent Kinase 5