Cyclin-dependent kinase inhibitor 2A (p16INK4a) (p16INK4a)

Cyclin-dependent kinase inhibitor 2A (p16INK4a) is a fundamental tumor suppressor protein that regulates the G1 to S phase transition of the cell cycle (Wikipedia, 2024). It acts by binding to and inhibiting the catalytic activity of cyclin-dependent kinases 4 and 6 (CDK4/6), which prevents the phosphorylation of the retinoblastoma (Rb) protein and subsequent E2F-mediated transcription of S-phase genes (UniProt, 2024). The p16INK4a pathway is one of the most frequently altered signaling cascades in human cancer, often inactivated through genetic deletion, mutation, or epigenetic silencing, which leads to unchecked cellular proliferation (NIH, 2014). Beyond oncology, p16INK4a is a primary marker of cellular senescence and biological aging, with its accumulation contributing to age-related tissue dysfunction (NIH, 2011). Therapeutic strategies involving this pathway include the use of CDK4/6 inhibitors to restore cell cycle control in p16-deficient tumors and the development of senolytic agents to selectively eliminate p16-positive senescent cells in aging-related pathologies (StatPearls, 2023).

Other names

p16CDKN2AMTS1CDK4IMultiple tumor suppressor 1p16INK4p16-INK4a

The p16INK4a protein inhibits CDK4 and CDK6, preventing the phosphorylation of the retinoblastoma (Rb) protein and arresting the cell cycle in G1. Drugs targeting this pathway include CDK4/6 inhibitors, which mimic p16 function to treat cancer, and senolytics, which selectively eliminate p16-expressing senescent cells by inducing apoptosis.