Phosphorylation of glucocorticoid receptor tau1c transactivation domain enhances binding to CREB binding protein (CBP) TAZ2

Carl W. Carruthers, Ji Ho Suh, Jan Ake Gustafsson, Paul Webb

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

The glucocorticoid receptor (GR) N-terminal domain (NTD) contains a transactivation domain (activation function 1; AF-1). GR AF-1 is phosphorylated, but effects of this modification upon AF-1 activity and cofactor recruitment are not completely clear. GR AF-1 activity is mostly confined to a short unstructured domain called tau1c (amino acids 187-244) that contains three phosphorylation sites and binds a short cysteine rich fragment (CH3) of the coactivator CREB binding protein (CBP). Since the CH3 domain overlaps the CBP transcriptional adaptor zinc binding (TAZ) 2 domain, implicated in phosphorylation dependent binding to other unstructured transcription factor domains, we set out to investigate whether GR interacts with TAZ2 and whether this binding event is modulated by phosphorylation. We find that GR tau1c is absolutely required for enhancement of GR function and GR/CBP association in cultured cells. Tau1c interacts with TAZ2 in vitro and peptide mapping reveals CBP binding determinants throughout tau1c. Phosphorylation at GR Ser203, not involved in transactivation, does not affect tau1c/TAZ2 interactions. However, phosphorylation at Ser211 and Ser226, markers of GR transcriptional activity, greatly enhances TAZ2 binding in a synergistic fashion. We propose that GR tau1c phosphorylation could promote CBP recruitment and enhance AF-1 activity.

Original languageEnglish (US)
Pages (from-to)119-123
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume457
Issue number1
DOIs
StatePublished - Jan 30 2015

Keywords

  • CREB binding protein
  • Coactivator
  • Gene expression
  • Glucocorticoid receptor
  • Phosphorylation
  • Protein biochemistry

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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