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Definition of the molecular basis for estrogen receptor-related receptor-alpha-cofactor interactions.

Publication ,  Journal Article
Gaillard, S; Dwyer, MA; McDonnell, DP
Published in: Mol Endocrinol
January 2007

Estrogen receptor-related receptor-alpha (ERRalpha) is an orphan nuclear receptor that does not appear to require a classical small molecule ligand to facilitate its interaction with coactivators and/or hormone response elements within target genes. Instead, the apo-receptor is capable of interacting in a constitutive manner with coactivators that stimulate transcription by acting as protein ligands. We have screened combinatorial phage libraries for peptides that selectively interact with ERRalpha to probe the architecture of the ERRalpha-coactivator pocket. In this manner, we have uncovered a fundamental difference in the mechanism by which this receptor interacts with peroxisome proliferator-activated receptor-gamma coactivator-1alpha, as compared with members of the steroid receptor coactivator subfamily of coactivators. Our findings suggest that it may be possible to develop ERRalpha ligands that exhibit different pharmacological activities as a consequence of their ability to differentially regulate coactivator recruitment. In addition, these findings have implications beyond ERRalpha because they suggest that subtle alterations in the structure of the activation function-2 pocket within any nuclear receptor may enable differential recruitment of coactivators, an observation of notable pharmaceutical importance.

Duke Scholars

Published In

Mol Endocrinol

DOI

ISSN

0888-8809

Publication Date

January 2007

Volume

21

Issue

1

Start / End Page

62 / 76

Location

United States

Related Subject Headings

  • Two-Hybrid System Techniques
  • Transcription, Genetic
  • Transcription Factors
  • Receptors, Estrogen
  • Protein Structure, Tertiary
  • Protein Binding
  • Promoter Regions, Genetic
  • Peptide Library
  • Molecular Sequence Data
  • Models, Molecular
 

Citation

APA
Chicago
ICMJE
MLA
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Gaillard, S., Dwyer, M. A., & McDonnell, D. P. (2007). Definition of the molecular basis for estrogen receptor-related receptor-alpha-cofactor interactions. Mol Endocrinol, 21(1), 62–76. https://doi.org/10.1210/me.2006-0179
Gaillard, Stéphanie, Mary A. Dwyer, and Donald P. McDonnell. “Definition of the molecular basis for estrogen receptor-related receptor-alpha-cofactor interactions.Mol Endocrinol 21, no. 1 (January 2007): 62–76. https://doi.org/10.1210/me.2006-0179.
Gaillard S, Dwyer MA, McDonnell DP. Definition of the molecular basis for estrogen receptor-related receptor-alpha-cofactor interactions. Mol Endocrinol. 2007 Jan;21(1):62–76.
Gaillard, Stéphanie, et al. “Definition of the molecular basis for estrogen receptor-related receptor-alpha-cofactor interactions.Mol Endocrinol, vol. 21, no. 1, Jan. 2007, pp. 62–76. Pubmed, doi:10.1210/me.2006-0179.
Gaillard S, Dwyer MA, McDonnell DP. Definition of the molecular basis for estrogen receptor-related receptor-alpha-cofactor interactions. Mol Endocrinol. 2007 Jan;21(1):62–76.

Published In

Mol Endocrinol

DOI

ISSN

0888-8809

Publication Date

January 2007

Volume

21

Issue

1

Start / End Page

62 / 76

Location

United States

Related Subject Headings

  • Two-Hybrid System Techniques
  • Transcription, Genetic
  • Transcription Factors
  • Receptors, Estrogen
  • Protein Structure, Tertiary
  • Protein Binding
  • Promoter Regions, Genetic
  • Peptide Library
  • Molecular Sequence Data
  • Models, Molecular