P14arf

P14arf is a tumor suppressor protein that in humans is encoded by the CDKN2A gene. This protein is an important regulator of the cell cycle and functions as a sensor of oncogenic signals, leading to cell cycle arrest.

Function

P14arf is a product of the CDKN2A locus, which generates two major transcripts through alternative splicing and use of different reading frames. The other product is p16INK4a, a cyclin-dependent kinase inhibitor. P14arf 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. With MDM2 sequestered, p53 can accumulate and act as a transcription factor to induce cell cycle arrest and apoptosis in response to DNA damage and oncogenic signals.

Clinical significance

Mutations in the CDKN2A gene, and therefore in the p14arf protein, are associated with a variety of cancers, including melanoma, pancreatic cancer, and lung cancer. These mutations often result in a loss of function of the p14arf protein, leading to uncontrolled cell proliferation.

See also

• CDKN2A
• p53
• MDM2
• Cell cycle
• Oncogene

References

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External links

• GeneCards - CDKN2A

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