Biological functions of CDK5 and potential CDK5 targeted clinical treatments.

Alison Shupp,Mathew C Casimiro,Richard G Pestell

doi:10.18632/oncotarget.14538

Alison Shupp, Mathew C Casimiro + Show 1 more

Open Access

https://doi.org/10.18632/oncotarget.14538

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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.

Highlights

Cyclin dependent kinases are proline-directed serine/threonine protein kinases that are traditionally activated upon association with a regulatory subunit
CDKs are a part of a kinase family that has been conserved throughout evolution and can be found in species from Saccharomyces cerevisia to humans
One study reported that this splice variant lacks 32 amino acids encoded by exon 7 [8], while another study stated the missing 32 amino acids are encoded by exon 6 [9]

Summary

INTRODUCTION

Cyclin dependent kinases are proline-directed serine/threonine protein kinases that are traditionally activated upon association with a regulatory subunit. In humans there are 13 different CDKs (CDK1 - CDK13) that are highly expressed in mitotic cells [1]. One study reported that this splice variant lacks 32 amino acids encoded by exon 7 [8], while another study stated the missing 32 amino acids are encoded by exon 6 [9] These two groups reported conflicting data, it has been suggested that the identified isoforms are the same protein and the variances in their data are due to different methodologies [10]. CDK5 has recently been implicated in diseases, including the development and progression of cancer and neurodegenerative diseases For this reason, the regulation of CDK5 activity is emerging as a candidate therapeutic target

Growth cone collapse

Cell proliferation

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Findings

CYTOSKELETAL ORGANIZATION