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Int J Biochem Cell Biol. 2006;38(10):1637-41. Epub 2006 Feb 28.

The ARF tumour suppressor.

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Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, Westmead Hospital, Westmead, NSW 2145, Australia.


The ARF tumour suppressor is a product of the INK4a/ARF locus; a sequence that is frequently altered in human cancer. ARF is upregulated by oncogenic stimuli and is a critical regulator of p53 stability through interactions with the mdm2 and ARF-BP1/Mule ubiquitin ligases. Cellular stress signals liberate ARF from the nucleolus where it is bound to B23/nucleophosmin. This nucleolar location of ARF may serve as a reservoir for the rapid induction of p53, but may also serve to co-ordinate effects on cell cycle, survival and growth. The biological functions of ARF interactions with other binding partners remain uncertain, but ARF-mediated sumoylation may represent a unifying effector pathway.

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