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Inhibition of Ribosome Biogenesis by p14(ARF)

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CDKN2A (Cyclin Dependent Kinase Inhibitor-2A) belongs to the CDKN family which show specificity for G1 phase CDKs (Cyclin-Dependent Kinases) and such binding results in block exit from G1 into S phase. CDKN2A, CDK4, CcnD (Cyclin-D) and Rb (Retinoblastoma) are components of the same growth-regulatory pathway that functions to control progression through G1 into S phase. CDKN2A is sometimes referred to as p16(INK4A) (Ref.1). Like p16(INK4A), ARFs (Alternative Reading Frames), or transcript variants of p16(INK4A) encodes p14(ARF), a tumor suppressor but its action is distinct from that of p16(INK4A). p16(INK4A) acts on the Rb pathway by inhibiting CDK4, whereas, p14(ARF) acts on the p53 pathway by interacting with MDM2 (Mouse Double Minute-2 Homolog), thereby blocking degradation of p53 and resulting in p53 stabilization and activation. Further more, binding of p14(ARF) to MDM2 results in sequestration of MDM2 in the [...]


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.Protecting p53 from degradation.
Lain S.
Biochem. Soc. Trans. 2003 Apr;31(2):482-5.
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