Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form

P53 latency - c-terminal domain prevents binding of p53 core to target but not to nonspecific DNA sequences

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Yakovleva, T.
  • Pramanik, A.
  • Kawasaki, T.
  • Tan-No, K.
  • Gileva, I.
  • Lindgren, H.
  • Langel, Ülo
  • Ekstrom, T. J.
  • Rigler, R.
  • Terenius, Lars
  • Bakalkin, G.

publication date

  • May 2001

journal

  • Journal of Biological Chemistry  Journal

abstract

  • The p53 transcription factor is either latent or activated through multi-site phosphorylation and acetylation of the negative regulatory region in its C-terminal domain (CTD). How CTD modifications activate p53 binding to target DNA sequences via its core domain is still unknown. It has been proposed that nonmodified CTD interacts either with the core domain or with DNA preventing binding of the core domain to DNA and that the fragments of the CTD regulatory region activate p53 by interfering with these interactions. We here characterized the sequence and target specificity of p53 activation by CTD fragments, interaction of activating peptides with p53 and target DNA, and interactions of "latent" p53 with DNA by a band shift assay and by fluorescence correlation spectroscopy. In addition to CTD fragments, several long basic peptides activated p53 and also transcription factor YY1. These peptides and CTD aggregated target DNA but apparently did not interact with p53. The potency to aggregate DNA correlated with the ability to activate p53, suggesting that p53 binds to target sequences upon interactions with tightly packed DNA in aggregates. Latent full-length p53 dissociated DNA aggregates via its core and CTD, and this effect was potentiated by GTP. Latent p53 also formed complexes via both its core and CTD with long nontarget DNA molecules. Such p53-DNA interactions may occur if latent p53 binding to DNA via CTD prevents the interaction of the core domain with target DNA sites but not with nonspecific DNA sequences.

subject areas

  • Amino Acid Sequence
  • Binding Sites
  • Consensus Sequence
  • DNA
  • Dynorphins
  • Guanosine Triphosphate
  • Humans
  • Kinetics
  • Molecular Sequence Data
  • Peptide Fragments
  • Recombinant Fusion Proteins
  • Recombinant Proteins
  • Spectrometry, Fluorescence
  • Substrate Specificity
  • Tumor Suppressor Protein p53
scroll to property group menus

Identity

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.M100482200

PubMed ID

  • 11279079
scroll to property group menus

Additional Document Info

start page

  • 15650

end page

  • 15658

volume

  • 276

issue

  • 19

©2021 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support