CDKN2A

(redirected from cyclin-dependent kinase inhibitor 2A)

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).
Segen's Medical Dictionary. © 2012 Farlex, Inc. All rights reserved.
References in periodicals archive ?
Recent molecular studies have demonstrated that mesotheliomas commonly show mutation or deletion of cyclin-dependent kinase inhibitor 2A (CDKN2A, p16) and BRCA-associated protein-1 (BAP1), and this information has been exploited through the use of p16 fluorescence in situ hybridization (FISH) analysis and BAP1 immunohistochemistry, where loss of either marker is a reliable indicator that a mesothelial proliferation is malignant.
For example, CDK4/6 inhibitors have promise as therapeutic interventions in the presence of alterations in various members of the CDK4/6 pathway, including cyclin D1 (CCND1), cyclin-dependent kinase inhibitor 2A (CDKN2A), cyclin-dependent kinase 4 (CDK4), and cyclin-dependent kinase 6 (CDK6) (16, 17).
Melanoma and breast cancer are fairly common bedfellows in familial cancer syndromes, and both types of cancer have been linked with mutations in cyclin-dependent kinase inhibitor 2A, a tumor suppressor gene, in some studies of familial cancer cohorts.
These candidate genes include DAPK (death-associated protein kinase 1), CDH1 [cadherin 1, type 1, E-cadherin (epithelial)], RASSF1 [Ras association (RalGDS/AF-6) domain family member 1], CDKN2A (cyclin-dependent kinase inhibitor 2A), FHIT (fragile histidine triad), MGMT (O6-methylguanine-DNA methyltransferase), and RARB (retinoic acid receptor, beta).
[2] Genes: Cdkn2a, cyclin-dependent kinase inhibitor 2A [Mus musculus gene]; Cdkn2b, cyclin-dependent kinase inhibitor 2B [Mus musculus gene]; CDKN2A, cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) [human gene]; CDKN2BB, cyclin-dependent kinase inhibitor 2B (melanoma, p16, inhibits CDK4) [human gene].

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