CDKN2Ap16INK4a

CDKN2Ap16INK4a, commonly known as p16INK4a, is a protein encoded by the CDKN2A gene located on chromosome 9p21. The CDKN2A gene produces two distinct tumor suppressor proteins, p16INK4a and p14ARF, from alternative reading frames, reflecting a complex locus involved in cell cycle control and tumor suppression.

p16INK4a inhibits the cyclin-dependent kinases 4 and 6 (CDK4/CDK6), preventing phosphorylation of the retinoblastoma (Rb) protein. By keeping Rb in a hypophosphorylated, active state, p16INK4a enforces G1 cell-cycle arrest in response to oncogenic stress or cellular signals, thereby limiting cell proliferation and helping maintain genomic integrity.

Expression of p16INK4a is associated with cellular aging and senescence. Loss or silencing of p16INK4a function—through mutations, deletions, or promoter methylation—is common in a range of cancers and can contribute to uncontrolled cell growth. In some tumors, p16INK4a status assists in diagnostic classification, and promoter methylation is a frequent mechanism of its silencing.

Clinical relevance includes the broader role of the p16INK4a pathway in cancer biology and aging. Therapeutic strategies that mimic p16INK4a function, such as CDK4/CDK6 inhibitors, are used in certain cancers. Assessment of CDKN2A/p16INK4a status can have prognostic value in some tumor types, and ongoing research seeks to clarify its regulation and interactions within the cellular stress response network.