Kinase Regulation in Cell Cycle and Cancer

Protein kinases orchestrate progression through the cell cycle by reversible phosphorylation of substrates that control DNA replication, mitotic entry, spindle assembly, and cytokinesis. Cyclin‐dependent kinases (CDKs), Polo‐like kinases (PLKs), Aurora kinases and NIMA‐related (NEK) kinases coordinate key transitions and checkpoints. Dysregulation of these enzymes can disrupt genomic integrity, promoting chromosomal instability and oncogenesis. Cross‐talk between kinase pathways, such as CDK–PLK coupling or NEK‐induced modulation of the Wnt/β‐catenin pathway, integrates cell‐cycle control with cellular growth signals. Aberrant kinase activation underlies many cancers, where overexpression, mutation or loss of regulatory mechanisms foster unchecked proliferation, impaired DNA damage responses and therapeutic resistance. Targeting kinase activity has therefore become central to anticancer drug development, offering routes to restore checkpoint fidelity, induce apoptosis or sensitise tumours to genotoxic treatments. Advances in structural biology, inhibitor design and pathway mapping continue to refine our understanding of kinase networks in both normal and malignant contexts.

Research from Nature Portfolio

Recent studies have elucidated the structural basis for activation and inhibition of NEK family kinases. A computational investigation of small molecules against NEK7 employed density functional theory, molecular docking and dynamics simulations to identify novel compounds that bind the NEK7 active site with high affinity and drug‐like properties, paving the way for targeted anti‐cancer agents. In parallel, crystallographic and biochemical analysis of the NEK9–NEK7 complex revealed an autoinhibitory tyrosine motif in NEK7 that is released through induced dimerisation upon NEK9 binding. This work uncovered a conserved back‐to‐back dimer interface that promotes kinase activation, offering insights into allosteric regulation applicable across diverse kinase families.

Kinase Regulation in Cell Cycle and Cancer publication trend

The graph below shows the total number of articles in kinase regulation in cell cycle and cancer across all publications each year (not limited to Nature Index journals).

Technical terms

Kinase: An enzyme that transfers phosphate groups to specific substrates, regulating protein activity.

Cyclin‐dependent kinase (CDK): A kinase whose activity is controlled by cyclin binding, driving cell‐cycle transitions.

NIMA‐related kinase (NEK): A family of serine/threonine kinases involved in mitotic regulation and checkpoint control.

Mitotic spindle: A microtubule‐based structure that segregates chromosomes during cell division.

Autoinhibition: A regulatory mechanism whereby a kinase’s own segment blocks its active site until relieved by binding or modification.

Wnt/β‐catenin signalling: A pathway in which Wnt ligands stabilise β‐catenin to regulate gene transcription, influencing proliferation and development.

References

1. NEK2 contributes to radioresistance in esophageal squamous cell carcinoma by inducing protective autophagy via regulating TRIM21. Cancer Cell International (2024).
2. NEK2 plays an essential role in porcine embryonic development by maintaining mitotic division and DNA damage response via the Wnt/β‐catenin signalling pathway. Cell Proliferation (2024).
3. NEK6 Regulates Redox Balance and DNA Damage Response in DU-145 Prostate Cancer Cells. Cells (2023).
4. Identification of potent inhibitors of NEK7 protein using a comprehensive computational approach. Scientific Reports (2022).
5. Mechanistic basis of Nek7 activation through Nek9 binding and induced dimerization. Nature Communications (2015).