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			PubMed Journals: J Biol Chem

  Source:		PMID: 17098746


    		J Biol Chem. 2007 Jan 19;282(3):1797-804.
     		Epub 2006 Nov 9.

			FBXO11 promotes the Neddylation of p53 and
			inhibits its transcriptional activity.

			Abida WM(1), Nikolaev A, Zhao W, Zhang W,
			Gu W.

			Author Information
			(1) Institute for Cancer Genetics and the
			Department of Pathology, College of Physicians
			& Surgeons, Columbia University, New York,
			New York 10032, USA.

			The p53 tumor suppressor is regulated by
			post-translational modification, including
			ubiquitination, phosphorylation and acetylation.
			It has previously been shown that the ubiquitin
			ligase Mdm2 also promotes the conjugation
			of Nedd8, a ubiquitin-like protein, to p53,
			inhibiting its transcriptional activity.
			We report the identification of FBXO11, a
			member of the F-box protein family and a
			component of the Skp1.Cullin1.F-box (SCF)
			complex, as a new p53-interacting protein.
			We show that FBXO11 promotes the neddylation
			of p53 both in vitro and in vivo. In addition
			to the C-terminal lysine residues, FBXO11 can
			also promote Nedd8 conjugation to Lys-320
			and Lys-321, and neddylation of p53 leads
			to suppression of p53 function. This is
			consistent with recent studies showing that
			a lysine to arginine mutation at Lys-320
			significantly enhances p53 function, although
			Lys-320 was originally identified as an
			acetylation site involving PCAF-mediated
			activation of p53. Our study provides an
			example of an F-box protein acting as an
			adaptor protein that can mediate the neddylation
			of a non-cullin substrate.

			DOI: 10.1074/jbc.M609001200 PMCID: PMC3690493
			PMID: 17098746 [Indexed for MEDLINE]

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