Cdk5 May Be an Atypical Kinase, but Not in the Way You Think

  • Li Wang
  • Jie Zhang
  • Karl Herrup


Cyclin-dependent kinase 5 (Cdk5) is a non-traditional CDK. It relies on two specific activators––p35 and p39––that are structurally similar to cyclins but genetically distinct. Analysis of the Cdk5 knockout (or the double p35/p39 knockout) has led to the view that the primary function of Cdk5 is in the migration and maturation of embryonic post-mitotic neurons. The literature has no reference to a role of Cdk5 in normal cell cycle regulation. Recent data from our lab, however, suggest that while it may not function as a traditional CDK and facilitate cell cycle progression, it does play a crucial role as a cell cycle suppressor in normal post-mitotic neurons. In this chapter, we review the evidence that this unique function is important for neuronal cell survival and differentiation. The action of Cdk5 in neurons appears to have sub-cellular specificity as well. We present early evidence that it is the nuclear form of Cdk5 that is crucial for holding the cell cycle in check. Cdk5 is found to exit the nucleus in stressed neurons at risk for death. 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


Cell Cycle Amyotrophic Lateral Sclerosis Focal Adhesion Kinase Cdk5 Activity Cell Cycle Protein 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



All three authors wish to acknowledge support during the writing of this review by grants from the NIH (NS20591 and AG24494).


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© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  1. 1.Department of Cell Biology and NeuroscienceNelson Biological Laboratories, Rutgers UniversityPiscatawayUSA

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