CDKN2A

(redirected from P16INK4a)
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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 ?
Evaluation of p16INK4a and pRb expression in cervical squamous and glandular neoplasia.
At the molecular level in primary GBMs, loss of heterozygosity (LOH) at 10q is the most frequent genetic alteration in primary GBMs observed in 69% patients, followed by EGFR amplification (34%), tumour protein 53 (TP53) mutations (31%), p16INK4a deletion (31%), and phosphatase and tensin homolog (PTEN) mutation (24%).
Evaluation of cervical cone biopsies for coexpression of p16INK4a and Ki-67 in epithelial cells.
Senescence is often associated with DNA Damage foci and it involves the cell cycle inhibitors p21WAF and P16INK4A together with other proteins, including senescence-associated b Galactosidases (SAbGal) and several cytokines.
K-ras and p16INK4A alterations in sputum of NSCLC patients and in heavy asymptomatic chronic smokers.
10) Although common etiological factors for both RCC and melanoma are not well-established, there are several possible links between these cancers, including: 1) exposure to shared environmental risk factors, such as obesity; (11) 2) shared genetic abnormalities, such as a common missense mutation in microphthalmia-associated transcription factor, (12) alterations in the CDKN2A gene encoding p16INK4a, (13) and increased association of familial RCC and melanoma; (14) 3) alterations in the MAPK pathway; (15) 4) alterations in cell-mediated immunity; (16) and 5) increased medical surveillance leading to increased incidental detection of RCC.
Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis during ageing.
Listado de genes susceptibles a hipermetilacion en su region promotora en cancer de pulmon Gen Locus CDKN2A/ 9p21 NSCLC60% p16INK4a SCLC 10 % FHIT 3p14.
Cyclin-dependent kinases (CDKs) contains kinase domain with little kinase activity but on binding with Cyclin, the Cyclin/CDK become an active complex and cause the hyperphosphorylation of pRB that ultimately involve in regulation of transcription and mRNA processing while Cyclin/CDK complex is itself regulated by cell cycle inhibitors of the INK4 (inhibitors of CDK4) and CIP/KIP (CDK interacting protein/kinase inhibitory protein) families, especially p16Ink4a and p21Cip1 (Dyer and Bremner, 2005; Sage, 2012).
Histone deacetylase inhibitor suppression of autoantibody-mediated arthritis in mice via regulation of p16INK4a and p21(WAF1/Cip1) expression.
A clinician seeking to identify a trial containing a CDK4/6 inhibitor for a patient with an alteration in CDKN2A, which is also known as P16, INK4, INK4A, ARF, and P16INK4A, would obtain variable results based on the gene name used in the search at ClinicalTrials.