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Nat Struct Mol Biol. 2010 Aug;17(8):982-9. doi: 10.1038/nsmb.1872. Epub 2010 Jul 18.

The C terminus of p53 binds the N-terminal domain of MDM2.

Author information

1
Department of Biological Sciences, Columbia University, New York, New York, USA.

Erratum in

  • Nat Struct Mol Biol. 2011 Apr;18(4):516.

Abstract

The p53 tumor suppressor interacts with its negative regulator Mdm2 via the former's N-terminal region and core domain, yet the extreme p53 C-terminal region contains lysine residues ubiquitinated by Mdm2 and can bear post-translational modifications that inhibit Mdm2-p53 association. We show that the Mdm2-p53 interaction is decreased upon deletion, mutation or acetylation of the p53 C terminus. Mdm2 decreases the association of full-length but not C-terminally deleted p53 with a DNA target sequence in vitro and in cells. Further, using multiple approaches, we show that a peptide from the p53 C terminus directly binds the Mdm2 N terminus in vitro. We also show that p300-acetylated p53 inefficiently binds Mdm2 in vitro, and Nutlin-3 treatment induces C-terminal modification(s) of p53 in cells, explaining the low efficiency of Nutlin-3 in dissociating p53-MDM2 in vitro.

PMID:
20639885
PMCID:
PMC2922928
DOI:
10.1038/nsmb.1872
[Indexed for MEDLINE]
Free PMC Article

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