Phosphorylation of glucocorticoid receptor tau1c transactivation domain enhances binding to CREB binding protein (CBP) TAZ2
| Autor: | Jan-Åke Gustafsson, Ji Ho Suh, Carl W. Carruthers, Paul Webb |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Transcriptional Activation
Molecular Sequence Data Biophysics environment and public health Biochemistry Cell Line Transactivation Phosphoserine Structure-Activity Relationship Glucocorticoid receptor Receptors Glucocorticoid Gene expression Coactivator Humans Amino Acid Sequence CREB-binding protein Phosphorylation Molecular Biology Transcription factor chemistry.chemical_classification biology Cell Biology CREB-Binding Protein Amino acid Cell biology Protein Structure Tertiary chemistry biology.protein Peptides Protein Binding |
| Zdroj: | Biochemical and biophysical research communications. 457(1) |
| ISSN: | 1090-2104 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect