Title:Overview of PCTK3/CDK18: A Cyclin-Dependent Kinase Involved in Specific Functions in Post-Mitotic Cells
Volume: 28
Issue: 33
Author(s): Rebeka de Oliveira Pepino, Fernanda Coelho, Tatiane Aparecida Buzanello Janku, Diandra Pinheiro Alencar, Walter Figueira de Azevedo*Fernanda Canduri*
Affiliation:
- Pontifical Catholic University of Rio Grande do Sul (PUCRS), School of Health and Life Sciences, Av. Ipiranga, 6681 Porto Alegre/RS 90619-900,Brazil
- Department of Chemistry and Molecular Physics, Sao Carlos Institute of Chemistry, University of Sao Paulo (USP), P.O. Box 780, Sao Carlos, 13560-970,Brazil
Keywords:
CDK18, PCTAIRE 3, DNA replication stress, transcription, cancer, Alzheimer's disease, PCTK3.
Abstract: Cyclin-dependent kinases (CDKs) comprise a family of about 20 serine/threonine
kinases whose catalytic activity requires a regulatory subunit known as cyclin; these
enzymes play several roles in the cell cycle and transcription. PCTAIRE kinases (PCTKs)
are a CDK subfamily, characterized by serine to cysteine mutation in the consensus PSTAIRE
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 thousands
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.