Activation of Estrogen Receptor Alpha by S118 Phosphorylation Involves a Ligand-Dependent Interaction With TFIIH and Participation of CDK7

Mol Cell. 2000 Jul;6(1):127-37.

Abstract

Phosphorylation of the estrogen receptor alpha (ERalpha) N-terminal transcription activation function AF1 at serine 118 (S118) modulates its activity. We show here that human ERalpha is phosphorylated by the TFIIH cyclin-dependent kinase in a ligand-dependent manner. Furthermore, the efficient phosphorylation of S118 requires a ligand-regulated interaction of TFIIH with AF2, the activation function located in the ligand binding domain (LBD) of ERalpha. This interaction involves (1) the integrity of helix 12 of the LBD/AF2 and (2) p62 and XPD, two subunits of the core TFIIH. These findings are suggestive of a novel mechanism by which nuclear receptor activity can be regulated by ligand-dependent recruitment of modifying activities, such as kinases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • COS Cells
  • Cyclin-Dependent Kinases*
  • Estrogen Receptor alpha
  • Humans
  • In Vitro Techniques
  • Ligands
  • Molecular Sequence Data
  • Phosphorylation
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • Protein-Serine-Threonine Kinases / metabolism*
  • Receptors, Estrogen / chemistry
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Serine / metabolism
  • Transcription Factor TFIIH
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription Factors, TFII*
  • Transcriptional Activation

Substances

  • Estrogen Receptor alpha
  • Ligands
  • Receptors, Estrogen
  • Recombinant Proteins
  • Transcription Factors
  • Transcription Factors, TFII
  • Transcription Factor TFIIH
  • Serine
  • Protein-Serine-Threonine Kinases
  • Cyclin-Dependent Kinases
  • cyclin-dependent kinase-activating kinase