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 ?
36) mesane tumorlu hastalarin idrar orneklerinde APC, RASSF1A ve p14ARF genleri ile yaptigi calismada da hipermetilasyonunun tumoru tespitinde sitolojiye ustun oldugu vurgulanmistir (%91-%50).
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].
Predictive significance of the alterations of p16INK4A, p14ARF, p53, and proliferating cell nuclear antigen expression in the progression of cervical cancer.
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.
APC-1A, p14ARF, p16INK4a, hMLH1, O6 MGMT, and RASSF1A) compared with people with high folate intake/ low alcohol intake (Van Engeland et al.
Hypermethylation of tumor suppressor genes (p16INK4A, p14ARF and APC) in adenocarcinomas of the upper gastrointestinal tract.
p14ARF and p16INK4a, two products of the same gene, are differently expressed in cervical intraepithelial neoplasia.
Loss of CDKN2A and p14ARF expression occurs frequently in human nonmelanoma skin cancers.
Por el contrario, se concluyo que era la activacion de p14ARF en las celulas prelinfoma, que ocurria en respuesta a mutaciones oncogenicas inducidas por la radiacion, la que en realidad conferia proteccion contra el desarrollo tumoral (37).