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Diversity in CDK structural mechanisms of regulation and drug discovery opportunities

Lookup NU author(s): Rhianna RowlandORCiD, Professor Martin NobleORCiD, Professor Jane EndicottORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

© 2025 The Author(s)Cyclin-dependent kinases (CDKs) are required for progression through the eukaryotic cell cycle and for gene transcription. The recent determination of structures of CDK-containing complexes by cryogenic electron microscopy has significantly enriched our understanding of the diverse mechanisms by which CDKs can be activated and regulated. Recent studies have also highlighted the importance of short linear motifs within CDK substrates and regulators to CDK activity. Aberrant CDK activity is a hallmark of a number of diseases, including cancers, and selective ATP-competitive inhibitors are in clinical use. Herein, we review recent structural insights into CDK activation and regulation and how these insights suggest alternative ways to modulate CDK activity that may lead to molecules with improved selectivity and/or specificity.

Publication metadata

Author(s): Rowland RJ, Noble MEM, Endicott JA

Publication type: Review

Publication status: Published

Journal: Trends in Biochemical Sciences

Year: 2026

Volume: 51

Issue: 3

Pages: 234-248

Print publication date: 01/03/2026

Online publication date: 19/02/2026

Acceptance date: 02/04/2018

ISSN (print): 0968-0004

ISSN (electronic): 1362-4326

Publisher: Elsevier Ltd

URL: https://doi.org/10.1016/j.tibs.2025.12.007

DOI: 10.1016/j.tibs.2025.12.007

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