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Latent and active p53 are identical in conformation

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  • A Ayed, University of Toronto, Unknown
  • F A Mulder
  • G S Yi, University of Toronto, Canada
  • Ying Lu, University of Toronto, Canada
  • L E Kay, University of Toronto, Canada
  • C H Arrowsmith, University of Toronto, Canada

p53 is a nuclear phosphoprotein that regulates cellular fate after genotoxic stress through its role as a transcriptional regulator of genes involved in cell cycle control and apoptosis. The C-terminal region of p53 is known to negatively regulate sequence specific DNA-binding of p53; modifications to the C-terminus relieve this inhibition. Two models have been proposed to explain this latency: (i) an allosteric model in which the C-terminal domain interacts with another domain of p53 or (ii) a competitive model in which the C-terminal and the core domains compete for DNA binding. We have characterized latent and active forms of dimeric p53 using gel mobility shift assays and NMR spectroscopy. We show on the basis of chemical shifts that dimeric p53 both containing and lacking the C-terminal domain are identical in conformation and that the C-terminus does not interact with other p53 domains. Similarly, NMR spectra of isolated core and tetramerization domains confirm a modular p53 architecture. The data presented here rule out an allosteric model for the regulation of p53.

Original languageEnglish
JournalNature Structural and Molecular Biology
Volume8
Issue9
Pages (from-to)756-760
Number of pages5
ISSN1072-8368
DOIs
Publication statusPublished - Sept 2001
Externally publishedYes

    Research areas

  • Allosteric Regulation, Binding Sites, DNA, Dimerization, Humans, Models, Biological, Nuclear Magnetic Resonance, Biomolecular, Peptide Fragments, Protein Binding, Protein Structure, Secondary, Protein Structure, Tertiary, Sequence Deletion, Tumor Suppressor Protein p53

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