Cyclin dependent kinase inhibitor 2A - Tumor Suppressor (Synonyms: H2N-Met-Val-Arg-Arg-Phe-Leu-Val-Thr-Leu-Arg-Ile-Arg-Arg-Ala-Cys-Gly-Pro-Pro-Arg-Val-OH )

Cyclin dependent kinase inhibitor 2A (CDKN2A, p16^Ink4A) (H2N-Met-Val-Arg-Arg-Phe-Leu-Val-Thr-Leu-Arg-Ile-Arg-Arg-Ala-Cys-Gly-Pro-Pro-Arg-Val-OH), also known as multiple tumor suppressor 1 (MTS-1), is a tumor suppressor protein, which in humans is encoded by the CDKN2A gene. [1][2] P16 plays an important role in regulating the cell cycle, and mutations in p16 increase the risk of developing a variety of cancers, notably melanoma. This gene is frequently mutated or deleted in a wide variety of tumors and is known to be an important tumor suppressor gene.

Mutations in the CDKN2A gene are associated with increased risk of a wide range of cancers, and alterations of the gene are frequently seen in cancer cell lines. [3] Examples include:

Pancreatic adenocarcinoma is often associated with mutations in the CDKN2A gene. [4] Homozygous deletion of p16 is frequently found in esophageal cancer and gastric cancer cell lines. [5]

Concentrations of p16INK4a increase dramatically as tissue ages. Consequently, p16INK4a could potentially be used as a blood test that measures how fast the body's tissues are aging at a molecular level. [6]

P16 (gene) also has been shown to interact with SERTAD1, CCNG1, Death associated protein 6, P53, E4F1, Cyclin-dependent kinase 4, Cyclin-dependent kinase 6, Mdm2, RPL11 and PPP1R9B. 

Fig 1. Structure of the CDKN2A protein.

Ref:

1. "Entrez Gene: CDKN2A cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4)"

2. Nobori T, Miura K, Wu DJ, Lois A, Takabayashi K, Carson DA (April 1994). "Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers". Nature 368 (6473): 753–6.

3. Liggett WH, Sidransky D (March 1998). "Role of the p16 tumor suppressor gene in cancer". J. Clin. Oncol. 16 (3): 1197–206.

4. Caldas C, Hahn SA, da Costa LT, Redston MS, Schutte M, Seymour AB, Weinstein CL, Hruban RH et al. (September 1994). "Frequent somatic mutations and homozygous deletions of the p16 (MTS1) gene in pancreatic adenocarcinoma". Nat. Genet. 8 (1): 27–32.

5. Igaki H, Sasaki H, Kishi T, Sakamoto H, Tachimori Y, Kato H, Watanabe H, Sugimura T et al. (September 1994). "Highly frequent homozygous deletion of the p16 gene in esophageal cancer cell lines". Biochem. Biophys. Res. Commun. 203 (2): 1090–5.

6. Liu Y, Sanoff HK, Cho H, Burd CE, Torrice C, Ibrahim JG, Thomas NE, Sharpless NE (May 2009). "Expression of p16INK4a in peripheral blood T-cells is a biomarker of human aging". Aging Cell 8 (4): 439–48.