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,
(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]