Overview of PCTK3/CDK18: A Cyclin-Dependent Kinase Involved in Specific Functions in Post-Mitotic Cells

Cyclin-dependent kinases (CDKs) comprise a family of about 20 serine/threo-nine kinases whose catalytic activity requires a regulatory subunit known as cyclin; these enzymes play several roles in the cell cycle and transcription. PCTAIRE kinases (PCTK-s) are a CDK subfamily, characterized by serine to cysteine mutation in the consensus PS-TAIRE motif, involved in binding to the cyclin. One member of this class is PCTK3, which has two isoforms (a and b) and is also known as CDK18. After being activated by cyclin A2 or phosphorylation at Ser12 by PKA, PCTK3 can perform several functions. Among these functions, we may highlight the following: modulation of cargo transport in membrane traffic, p53-responsive gene, regulation of genome integrity. According to different studies, PCTK3 dysfunction is related to a wide range of diseases, such as metabolic diseases, cerebral ischemia, depression, cancer, neurological disorders, and Alzheimer's disease. Although this protein participates in different biological events, we may say that PCTK3 has received far less attention than other CDKs. There are thou-sands of published articles about other CDKs and less than two hundred articles related to PCTK3. The main objective of this review is to present the selected published studies about this protein. Our focus is on PCTK3 particularities compared to other CDKs. Here we give an overview of the biological functions of PCTK3 and explore its potential as a target for drug design.

Automated summary

Cyclin-dependent kinases (CDKs) are a family of serine/threonine kinases, with PCTAIRE kinases being a subfamily. PCTK3, a member of this subfamily, plays various roles in the cell cycle and transcription. Its functions include modulation of cargo transport, regulation of p53-responsive genes, and maintenance of genome integrity. Dysregulation of PCTK3 is associated with metabolic diseases, cerebral ischemia, depression, cancer, neurological disorders, and Alzheimer's disease, yet it has received less research attention compared to other CDKs.