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 ?
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).
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.
Evaluation of genetic association of the INK4 locus with primary open angle glaucoma in East Indian population.
This might affect cell senescence because P15-INK4b, a CDK inhibitor in the INK4 family of proteins, is a tumor suppressor (Thillainadesan et al.
By contrast, mice expressing a Cdk4 mutation that prevents binding to INK4 inhibitors, show pancreatic hyperplasia due to abnormal [beta]-cell proliferation (9).
Structural basis of inhibition of CDK-cyclin complexes by INK4 inhibitors.
Homozygous inactivation of p16 INK4 gene has been reported in childhood ALL by several researchers (Okuda et al.
Many of which directly interact with critical regulators such as PTEN, Myc, Ras or ABL as well as members of the Rb pathway, Cyclin-CDK complexes or cell cycle inhibitors of INK4 or Cip/Kip families to modulate cell proliferation pathways (39).
The p16 tumor suppressor gene, a member of the INK4 class of cell-cycle inhibitors, is a critical component of the Rb pathway.
Mechanisms ofcyclin-dependent kinase regulation: structures of Cdks, their cyclin activators, and Cip and INK4 inhibitors.
The region consists of CDKN2B-AS [3] [CDKN2B antisense RNA (non-protein coding), also known as ANRIL (antisense RNA in the INK4 locus)], which encodes an antisense noncoding RNA spanning 126 000 bp (41).