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 ?
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.
Promotor hypermethylation of p14ARF is a key alteration for progression of oral squamous cell carcinoma.
102) Hypermethylation of p14ARF was detected in 50% of UC-associated adenocarcinomas, 33% of dysplasia lesions, and 60% of noncancerous but inflamed samples.
Adenovirus-mediated p14ARF gene transfer in human mesothelioma cells.
p14ARF modulates the cytolytic effect of ONYX-015 in mesothelioma cells with wild-type p53.
The relationship between tumor suppressor genes p14ARF and p53 expression and biological behavior of pancreatic carcinoma [in Chinese].
from Immunohistochemical Analysis of p18INK4C and p14ARF Protein Expression in 117 Oligodendrogliomas--Korshunov & Golanov) Answer to this month's questions: 1, e.
8,9) As recently discovered, the CDKN2A locus encodes for 2 gene products, p16INK4A and p14ARF.
The p14ARF gene product is a protein with a molecular weight of approximately 14 kd, and it is encoded by exon 1b of the CDKN2A gene.
Recent reports strongly suggest an important role of p14ARF gene mutations in the biology of various human malignancies, including astrocytic neoplasms.
In the present study, biopsy samples of 117 oligodendrogliomas were examined immunohistochemically to evaluate a possible association between expression of p18INK4C and p14ARF proteins and patient survival.