CDKN2A

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CDKN2A

A gene on chromosome 9p21 that encodes an alternate open reading frame (ARF) product, which acts as a tumour suppressor by binding to MDM2 and blocking its nucleocytoplasmic shuttling by sequestering it in the nucleolus. This inhibits MDM2’s oncogenic activity, which would normally degrade p53, a tumour suppressor protein. CDKN2A also induces G2 arrest and apoptosis, independent of p53, by preventing the activation of cyclin B1/CDC2 complexes.

CDKN2A also binds to:
• BCL6, downregulating BCL6-induced transcriptional repression;
• E2F1 and MYC, blocking their transcriptional activator activity;
• HUWE1, repressing its ubiquitin ligase activity;
• TOP1/TOPOI, stimulating its activity. This complex binds to rRNA gene promoters and may play a role in rRNA transcription and/or maturation.

CDKN2A interacts with:
• COMMD1 and promotes its “Lys63”-linked polyubiquitination;
• NPM1/B23, promoting its polyubiquitination and degradation and inhibiting rRNA processing;
• UBE2I/UBC9, enhacing sumoylation of some of its binding partners (e.g., MDM2 and E2F1).
References in periodicals archive ?
Spandidos, "Deregulation of the tumour suppressor genes p14ARF, p15 INK4b, p16INK4a and p53 in basal cell carcinoma," British Journal of Dermatology, vol.
A novel proapoptotic gene PANO encodes a post-translational modulator of the tumor suppressor p14ARF. Exp Cell Res 2012; 318: 187-195.
P14ARF has been found to bind to the MDM2/p53 complex and inhibit the MDM2-degradation of p53.
Epigenetic regulation of p14ARF and p16INK4A expression in cutaneous and uveal melanoma.
Yu et al., "Promoter hypermethylation of p14ARF, RB, and INK4 gene family in hepatocellular carcinoma with hepatitis B virus infection," Tumor Biology, vol.
Belge et al., "HMGA2 and p14Arf: Major roles in cellular senescence of fibroids and therapeutic implications," Anticancer Research, vol.
Immunohistochemical analysis of p16INK4a, p14ARF, p18INK4c, p21CIP1, p27KIP1 and p73 expression in 271 meningiomas correlation with tumor grade and clinical outcome.
Gen CDKN2A koduje 2 bialka - p16INK4A hamujace fosforylacje bialka pRb i p14ARF o alternatywnej ramce odczytu (alternative reading frame), ktore zwieksza aktywnosc bialka p53.
Germline mutations in cyclin-dependent kinase inhibitor 2A (CDKN2A), a kinase that plays a role in UV-induced melanin production by encoding two different tumor suppressor genes, p16INK4a and p14ARF, are associated with familial melanoma [35].
Kaneko, "Analysis of the p16INK4, p14ARF, p15, TP53, and MDM2 genes and their prognostic implications in osteosarcoma and Ewing sarcoma," Cancer Genetics and Cytogenetics, vol.
Epigenetic changes in the CDKN2A locus are associated with differential expression of P16INK4A and P14ARF in HPV positive oropharyngeal squamous cell carcinoma [published online ahead of print January 26, 2015].