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).
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