The N-terminal interferon-binding domain (IBiD) homology domain of p300 binds to peptides with homology to the p53 transactivation domain.

The Journal of Biological Chemistry
Lee Finlan, Ted R Hupp

Abstract

Two high affinity Ser-20-phospho-LXXLL p53-binding domains of p300 map to the C-terminal interferon-binding domain (IBiD) and N-terminal IBiD homology domain (IHD) regions. Purified fractions of a recombinant IHD miniprotein are active in a set of in vitro assays highlighting its affinity to the N-terminal LXXLL domain of p53 including (i) dose-dependent binding to Ser-20-phosphorylated p53 tetramers; (ii) DNA-stimulated binding to p53 tetramers; and (iii) inhibition of MDM2-mediated p53 ubiquitination. The active component of the IHD miniprotein was localized to a 75-amino-acid fragment corresponding to amino acids 401-475 on human p300. This minimal IHD miniprotein can function in vivo as a p53-binding polypeptide in assays including: (i) complex formation with VP16-LXXLL peptide motifs in the two-hybrid assay; (ii) action as a dominant negative inhibitor of p53 from p21 luciferase templates; and (iii) attenuation of endogenous p21 protein levels. Further, we show here that the IRF-1-dependent stabilization and reactivation of p53DeltaPRO protein (LXXLL+/PXXP-) can be neutralized by the minimal IHD miniprotein, suggesting that IHD can bind to the p53 LXXLL domain in vivo. Phage-peptide display to the IHD miniprotein gave rise...Continue Reading

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Citations

May 8, 2010·The Journal of Biological Chemistry·Emily B AskewElizabeth M Wilson
May 12, 2010·Cold Spring Harbor Perspectives in Biology·David W Meek, Carl W Anderson
Oct 20, 2005·Journal of Bioscience and Bioengineering·Fumiaki UchiyamaNoritaka Tokui
Apr 18, 2007·Proceedings of the National Academy of Sciences of the United States of America·Daniel P TeufelAlan R Fersht
Dec 25, 2007·Journal of Molecular Biology·Smarajit PolleySiddhartha Roy
Nov 24, 2004·Molecular Microbiology·S E Perry, D H Edwards
Jan 16, 2008·The Journal of Biological Chemistry·Ben HarrisonTed R Hupp
Jan 23, 2020·Ethics & Human Research·Adrian Kwek

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