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

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.
Mesh Terms:
Apoptosis, Arginine, Cell Cycle Proteins, Cullin Proteins, F-Box Proteins, Hela Cells, Histone Acetyltransferases, Humans, Lysine, Protein Binding, Protein Structure, Tertiary, Protein-Arginine N-Methyltransferases, SKP Cullin F-Box Protein Ligases, Transcription Factors, Transcription, Genetic, Tumor Suppressor Protein p53, Ubiquitin, Ubiquitins, p300-CBP Transcription Factors
J. Biol. Chem.
Date: Jan. 19, 2007
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