New Insights into CDK Regulators: Novel Opportunities for Cancer Therapy.

ABSTRACT

Cyclins and their catalytic partners, the cyclin-dependent kinases (CDKs), control the transition between different phases of the cell cycle. CDK/cyclin activity is regulated by CDK inhibitors (CKIs), currently comprising the CDK-interacting protein/kinase inhibitory protein (CIP/KIP) family and the inhibitor of kinase (INK) family. Recent studies have identified a third group of CKIs, called ribosomal protein-inhibiting CDKs (RPICs). RPICs were discovered in the context of cellular senescence, a stable cell cycle arrest with tumor-suppressing abilities. RPICs accumulate in the nonribosomal fraction of senescent cells due to a decrease in rRNA biogenesis. Accordingly, RPICs are often downregulated in human cancers together with other ribosomal proteins, the tumor-suppressor functions of which are still under study. In this review, we discuss unique therapies that have been developed to target CDK activity in the context of cancer treatment or senescence-associated pathologies, providing novel tools for precision medicine.