p16

p16 most commonly refers to p16INK4a, a cyclin-dependent kinase inhibitor encoded by the CDKN2A gene on chromosome 9p21.3. p16INK4a inhibits CDK4 and CDK6, preventing phosphorylation of the retinoblastoma (RB) protein and blocking progression from G1 to S phase. The CDKN2A locus also encodes p14ARF through an alternative reading frame; p14ARF stabilizes p53 by inhibiting MDM2, linking RB and p53 tumor suppressor pathways.

Function and regulation: p16INK4a is a key regulator of cellular senescence and aging. Its expression increases in response to cellular stress and contributes to the growth arrest that limits cell proliferation. In the absence of functional p16INK4a, cells are more prone to unchecked division.

Clinical significance: In cancer, CDKN2A/p16INK4a is frequently inactivated by deletions, mutations, or promoter methylation, contributing to uncontrolled cell growth. p16INK4a is also used as a diagnostic biomarker: high levels of p16INK4a detected by immunohistochemistry serve as a surrogate marker for oncogenic high-risk HPV infection in cervical and oropharyngeal cancers, reflecting HPV-driven carcinogenesis.

Genetics: The CDKN2A gene is a tumor suppressor locus at 9p21.3. Germline mutations in CDKN2A confer increased risk of familial melanoma and, to a lesser extent, pancreatic cancer; somatic alterations are common in sporadic cancers.

See also: p14ARF, RB pathway, HPV-related cancers.