P16 (gene)

Cyclin-dependent kinase inhibitor 2A, (CDKN2A, p16Ink4A) also known as multiple tumor suppressor 1 (MTS-1), is a tumor suppressor is_associated_with::protein, that in humans is encoded by the CDKN2A is_associated_with::gene. P16 plays an important role in regulating the is_associated_with::cell cycle, and is_associated_with::mutations in p16 increase the risk of developing a variety of is_associated_with::cancers, notably is_associated_with::melanoma.

Function
This is_associated_with::gene generates several transcript variants that differ in their first is_associated_with::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 is_associated_with::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.

Increased expression of the p16 gene as organisms age reduces the proliferation of stem cells. This reduction in the division and production of stem cells protects against is_associated_with::cancer while increasing the risks associated with cellular senescence.

Clinical significance
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 is_associated_with::cell lines. Examples include:

Pancreatic adenocarcinoma is often associated with mutations in the CDKN2A gene.

Homozygous deletion of p16 are frequently found in is_associated_with::esophageal cancer and is_associated_with::gastric cancer cell lines.

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

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