Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 282, Issue 3, Pages 1797-1804Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M609001200
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Funding
- NCI NIH HHS [R01 CA098821, R01 CA129627, R01 CA118561, R01 CA131439, R01 CA104843, R01 CA085533] Funding Source: Medline
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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 center dot Cullin1 center dot 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.
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