A point mutation of the AF2 transactivation domain of the glucocorticoid receptor disrupts its interaction with steroid receptor coactivator 1

Tomas Kucera; Mary Waltner-Law; Donald K Scott; Ratna Prasad; Daryl K Granner

doi:10.1074/jbc.M204013200

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A point mutation of the AF2 transactivation domain of the glucocorticoid receptor disrupts its interaction with steroid receptor coactivator 1

Journal article

Open access

Peer reviewed

A point mutation of the AF2 transactivation domain of the glucocorticoid receptor disrupts its interaction with steroid receptor coactivator 1

Tomas Kucera, Mary Waltner-Law, Donald K Scott, Ratna Prasad and Daryl K Granner

The Journal of biological chemistry, Vol.277(29), pp.26098-26102

07/19/2002

DOI: 10.1074/jbc.M204013200

PMID: 12118039

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Abstract

Glucocorticoids cause a 10-fold increase in hepatic phosphoenolpyruvate carboxykinase (PEPCK) gene transcription through two low affinity glucocorticoid receptor (GR) binding sites and a complex array of accessory factor DNA elements and associated proteins. To analyze how co-activators interact with the GR in this context, we took advantage of the C656G GR mutant that binds ligand with very high affinity. This GR activates PEPCK gene transcription at a 500-fold lower dexamethasone concentration than does wild type GR. Transfected C656G GR containing additional mutations or deletions was tested on PEPCK gene expression in H4IIE hepatoma cells. We found that the AF2 domain is the only one of the three defined transactivation domains in GR that is required for PEPCK gene expression and that mutation of this domain disrupts the direct interaction of GR with steroid receptor coactivator 1 (SRC-1). These data help define the functional interaction between GR and SRC-1 and further define the role of the GR in glucocorticoid-mediated expression of the PEPCK gene.

Yeasts

Transcriptional Activation - genetics

Histone Acetyltransferases

Humans

Protein-Serine-Threonine Kinases - genetics

Structure-Activity Relationship

Blotting, Western

Gene Expression Regulation, Enzymologic

Transcription Factors - metabolism

Point Mutation

Animals

Transfection

Receptors, Glucocorticoid - genetics

Nuclear Receptor Coactivator 1

Binding Sites

COS Cells

Details

Title: Subtitle: A point mutation of the AF2 transactivation domain of the glucocorticoid receptor disrupts its interaction with steroid receptor coactivator 1
Creators: Tomas Kucera - Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee 37232-0615, USA
Mary Waltner-Law
Donald K Scott
Ratna Prasad
Daryl K Granner
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.277(29), pp.26098-26102
DOI: 10.1074/jbc.M204013200
PMID: 12118039
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: United States
Language: English
Date published: 07/19/2002
Academic Unit: Molecular Physiology and Biophysics
Record Identifier: 9984020619102771

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