FBXO11 promotes the neddylation of p53 and inhibits its transcriptional activity Academic Article uri icon

Overview

MeSH Major

  • F-Box Proteins
  • Protein-Arginine N-Methyltransferases
  • Transcription, Genetic
  • Tumor Suppressor Protein p53
  • Ubiquitins

abstract

  • 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.

publication date

  • January 19, 2007

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3690493

Digital Object Identifier (DOI)

  • 10.1074/jbc.M609001200

PubMed ID

  • 17098746

Additional Document Info

start page

  • 1797

end page

  • 804

volume

  • 282

number

  • 3