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Inhibition of Ribosome Biogenesis by p19(ARF)

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Description

CDKN2A (Cyclin Dependent Kinase Inhibitor-2A), which is also referred to as p16(INK4A) encodes ARFs (Alternative Reading Frames), or transcript variants. In mice the p16(INK4A) encodes a transcript variant known as p19(ARF), whereas in humans it encodes p14(ARF). The p19(ARF) acts a tumor suppressor but its action is distinct from the murine p16(INK4A). p19(ARF) acts on the p53 pathway by interacting with MDM2 (Mouse Double Minute-2), thereby blocking degradation of p53 and resulting in p53 stabilization and activation. This prevents shuttling of MDM2 between nucleus and cytoplasm (to where it must export p53 for degradation), thereby leaving p53 free within the nucleus to transactivate transcription of responsive genes. Interestingly, p19(ARF) is required for p53 activation by proliferative signals such as Myc (Myelocytomatosis Oncogene) but not for activation in response to ultraviolet or ionizing radiation. In addition p19(ARF) is also [...]

References:

1.A germline deletion of p14(ARF) but not CDKN2A in a melanoma-neural system tumour syndrome family.
Randerson-Moor JA, Harland M, Williams S, Cuthbert-Heavens D, Sheridan E, Aveyard J, Sibley K, Whitaker L, Knowles M, Bishop JN, Bishop DT.
Hum. Mol. Genet. 2001 Jan 1;10(1):55-62.
2.p53 is covalently linked to 5.8S rRNA.
Fontoura BM, Sorokina EA, David E, Carroll RB.
Mol. Cell Biol. 1992 Nov;12(11):5145-51.
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