CDKN2A

(redirected from P19ARF)

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 ?
shRNA kullanilarak olusturulan bir model p19ARF olup, bu modellerde akciger adenokarsinoma gozlemlenmis ve terapotik olarak kullanilmistir (70).
In addition, several tumor-suppressor-related and cell-death-related proteins, including DAPK, DRP1, ZIP, p19ARF, and GBA, triggered autophagic cell death (2,45-48).
Morrison, "Hmga2 promotes neural stem cell self-renewal in young but not old mice by reducing [p16.sup.INK4a] and p19Arf Expression," Cell, vol.
Morrison, "Hmga2 promotes neural stem cell self-renewal in young but not old mice by reducing p16Ink4a and p19Arf expression," Cell, vol.
Deletion of cDkN2A disrupts two encoded proteins (p16INK4A and p19ARF) and their associated regulatory cascades.
Mikulits, "Liver sinusoidal endothelial cells escape senescence by loss of p19ARF," PLoS ONE, vol.
Perez-Romero et al., "Direct promoter induction of p19Arf by Pit-1 explains the dependence receptor RET/Pit-1/p53-induced apoptosis in the pituitary somatotroph cells," Oncogene, vol.
Opposing roles for p16Ink4a and p19Arf in senescence and ageing caused by BubR1 insufficiency.
Debido a que el supresor tumoral p53 regula negativamente el supresor ARF (p14ARF en humanos y p19ARF en ratones), ha sido sugerido que el silenciamiento o inhibicion de p53 induce autofagia por un incremento en la expresion de ARF, regulador positivo de autofagia cuando se une a Bcl-xL y limita la union de este a Beclina1 induciendo la formacion del autofagosoma (84-86).
The human p19ARF protein encoded by the beta transcript of the p16INK4a gene is frequently lost in small cell lung cancer.
Other models are also under evaluation at the NIEHS/NTP (p16Ink4a and p19Arf deficient mice) or elsewhere (XPA-Trp53 deficient mice).
Vinue et al., "p19ARF deficiency reduces macrophage and vascular smooth muscle cell apoptosis and aggravates atherosclerosis," Journal of the American College of Cardiology, vol.