Role of Intrinsic Protein Disorder in the Function and Interactions of the Transcriptional Coactivators CREB-binding Protein (CBP) and p300

J Biol Chem. 2016 Mar 25;291(13):6714-22. doi: 10.1074/jbc.R115.692020. Epub 2016 Feb 5.

Abstract

The transcriptional coactivators CREB-binding protein (CBP) and p300 undergo a particularly rich set of interactions with disordered and partly ordered partners, as a part of their ubiquitous role in facilitating transcription of genes. CBP and p300 contain a number of small structured domains that provide scaffolds for the interaction of disordered transactivation domains from a wide variety of partners, including p53, hypoxia-inducible factor 1α (HIF-1α), NF-κB, and STAT proteins, and are the targets for the interactions of disordered viral proteins that compete with cellular factors to disrupt signaling and subvert the cell cycle. The functional diversity of the CBP/p300 interactome provides an excellent example of the power of intrinsic disorder to facilitate the complexity of living systems.

Keywords: IDP; IDR; STAT transcription factor; cAMP response element-binding protein (CREB); coupled folding and binding; hypoxia-inducible factor (HIF); intrinsically disordered protein; intrinsically disordered region; protein-protein interaction; structure-function; transcriptional activation; transcriptional coactivator; viral oncoprotein.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • CREB-Binding Protein / chemistry*
  • CREB-Binding Protein / genetics
  • CREB-Binding Protein / metabolism
  • E1A-Associated p300 Protein / chemistry*
  • E1A-Associated p300 Protein / genetics
  • E1A-Associated p300 Protein / metabolism
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / chemistry
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Intrinsically Disordered Proteins / chemistry*
  • Intrinsically Disordered Proteins / genetics
  • Intrinsically Disordered Proteins / metabolism
  • Models, Molecular
  • NF-kappa B / chemistry
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Protein Binding
  • Protein Folding
  • Protein Interaction Domains and Motifs
  • Protein Structure, Secondary
  • STAT Transcription Factors / chemistry
  • STAT Transcription Factors / genetics
  • STAT Transcription Factors / metabolism
  • Transcription, Genetic
  • Tumor Suppressor Protein p53 / chemistry
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Viral Proteins / chemistry*
  • Viral Proteins / genetics
  • Viral Proteins / metabolism

Substances

  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Intrinsically Disordered Proteins
  • NF-kappa B
  • STAT Transcription Factors
  • Tumor Suppressor Protein p53
  • Viral Proteins
  • CREB-Binding Protein
  • CREBBP protein, human
  • E1A-Associated p300 Protein
  • EP300 protein, human

Associated data

  • PDB/1L8C
  • PDB/2KA6