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 ?
For non-FIPV-related cancers, which account for the majority of head and neck tumors, they looked for mutations in cancer-related genes that included TP53, PIK3CA, CDKN2A, FBXW7, HRAS, and NRAS.
The most common clinically relevant GAs were KRAS (16%), CDKN2A (14%), CCND1 (9.
2012) using a lookup approach in our data set for DAPK1, CDKN2A (P16), GMDS, C10orf32/AS3MT, RASSF1, PPARG, TP53, and MLH1 (see Supplemental Material, Table S3).
The germline mutation on VHL is a cause of von Hippel-Lindau syndrome); CCND1, cyclin D1 (cyclin D1 controls cell cycle by regulating CDK4 and CDK6 activity which is required for G1/S transition); CDKN2A, cyclin dependent kinase inhibitor 2A (cyclin dependent kinase inhibitor 2A regulates cell cycle G1 progression by inhibiting CDK4 kinase.
INK4a] is a cyclin-dependent kinase inhibitor that inhibits cyclin dependent kinase 4 and 6, a product of the CDKN2A (INK4a) gene, involved in the phosphorylation of the retinoblastoma protein (Rb).
For example, we know a faulty CDKN2A and CDK4 gene indicates that you're at greater risk for melanoma.
Deletions of the 9p21 chromosomal region are frequent in childhood ALL and encompass CDKN2A (MTS1), a gene encoding both pl6INK4a and p14ARF p16INK4a, an inhibitor of cyclin-dependent kinase, inhibits Rb phosphorylation, whereas p14ARF activates TP53 via interaction with the MDM2 protein 1.
Dual-color FISH analysis was performed with a Spectrum Green-labeled chromosome 9 centromeric probe and a Spectrum Orange-labeled, locus-specific CDKN2A (p16) probe (Vysis, Downers Grove, Illinois).
Genes exhibiting hypermethylation included RASSF1, APC, and CDKN2A, all of which have important functions in the liver (Tischoff and Tannapfel 2008).
For example, the TP53 gene was altered in 90 percent of the tumours and the CDKN2A gene was inactivated in 72 percent of tumours.
Inactivation of the CDKN2A gene by deletion of chromosome 9p21.
Although the tumor suppressor genes CDKN2A and CDKN2B are located in this region, the specific gene(s) and/or biological mechanism underlying this risk association is still unknown.