Structure of the Tfb1/p53 complex: Insights into the interaction between the p62/Tfb1 subunit of TFIIH and the activation domain of p53

Mol Cell. 2006 Jun 23;22(6):731-40. doi: 10.1016/j.molcel.2006.05.007.

Abstract

The interaction between the amino-terminal transactivation domain (TAD) of p53 and TFIIH is directly correlated with the ability of p53 to activate both transcription initiation and elongation. We have identified a region within the p53 TAD that specifically interacts with the pleckstrin homology (PH) domain of the p62 and Tfb1 subunits of human and yeast TFIIH. We have solved the 3D structure of a complex between the p53 TAD and the PH domain of Tfb1 by NMR spectroscopy. Our structure reveals that p53 forms a nine residue amphipathic alpha helix (residues 47-55) upon binding to Tfb1. In addition, we demonstrate that diphosphorylation of p53 at Ser46 and Thr55 leads to a significant enhancement in p53 binding to p62 and Tfb1. These results indicate that a phosphorylation cascade involving Ser46 and Thr55 of p53 could play an important role in the regulation of select p53 target genes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Expression Regulation / physiology
  • Humans
  • Models, Molecular*
  • Multiprotein Complexes / chemistry*
  • Multiprotein Complexes / metabolism
  • Nuclear Magnetic Resonance, Biomolecular
  • Phosphorylation
  • Protein Structure, Quaternary
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Saccharomyces cerevisiae / chemistry
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Structural Homology, Protein
  • Transcription Factor TFIIH / chemistry*
  • Transcription Factor TFIIH / metabolism
  • Transcription Factors, TFII / chemistry*
  • Transcription Factors, TFII / metabolism
  • Transcription, Genetic / physiology
  • Tumor Suppressor Protein p53 / chemistry*
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Multiprotein Complexes
  • Saccharomyces cerevisiae Proteins
  • TFB1 protein, S cerevisiae
  • Transcription Factors, TFII
  • Tumor Suppressor Protein p53
  • Transcription Factor TFIIH

Associated data

  • PDB/2GS0