P16

Cyclin-dependent kinase inhibitor 2a p19Arf N-terminus
solution structure of the n-terminal 37 amino acids of the mouse arf tumor suppressor protein
Identifiers
Symbol	P19Arf_N
Pfam	PF07392
InterPro	IPR010868
SCOP	1hn3
SUPERFAMILY	1hn3
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

p16 (also known as cyclin-dependent kinase inhibitor 2A, multiple tumor suppressor 1 and as several other synonyms), is a tumor suppressor protein, that in humans is encoded by the CDKN2A gene. p16 plays an important role in cell cycle regulation by decelerating cells progression from G1 phase to S phase, and therefore acts as a tumor suppressor that is implicated in the prevention of cancers, notably melanoma, oropharyngeal squamous cell carcinoma, cervical cancer, and esophageal cancer. p16 can be used to improve the histological diagnostic accuracy of CIN3. The CDKN2A gene is frequently mutated or deleted in a wide variety of tumors.

p16 is an inhibitor of cyclin dependent kinases such as CDK4 and CDK6. These latter kinases phosphorylate retinoblastoma protein (pRB) which eventually results in progression from G1 phase to S phase.

p16 was originally found in an “open reading frame of 148 amino acids encoding a protein of molecular weight 15,845 comprising four ankyrin repeats.” p16Ink4A is named after its molecular weight and its role in inhibiting CDK4.

p16 is also known as:

In humans, p16 is encoded by the CDKN2A gene, located on chromosome 9 (9p21.3). This gene generates several transcript variants that differ in their first exons. At least three alternatively spliced variants encoding distinct proteins have been reported, two of which encode structurally related isoforms known to function as inhibitors of CDK4. The remaining transcript includes an alternate exon 1 located 20 kb upstream of the remainder of the gene; this transcript contains an alternate open reading frame (ARF) that specifies a protein that is structurally unrelated to the products of the other variants. The ARF product functions as a stabilizer of the tumor suppressor protein p53, as it can interact with and sequester MDM2, a protein responsible for the degradation of p53. In spite of their structural and functional differences, the CDK inhibitor isoforms and the ARF product encoded by this gene, through the regulatory roles of CDK4 and p53 in cell cycle G1 progression, share a common functionality in control of the G1 phase of the cell cycle. This gene is frequently mutated or deleted in a wide variety of tumors and is known to be an important tumor suppressor gene.