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Use of phage display to identify novel mineralocorticoid receptor-interacting proteins.

Publication ,  Journal Article
Yang, J; Fuller, PJ; Morgan, J; Shibata, H; McDonnell, DP; Clyne, CD; Young, MJ
Published in: Mol Endocrinol
September 2014

The mineralocorticoid receptor (MR) plays a central role in salt and water homeostasis via the kidney; however, inappropriate activation of the MR in the heart can lead to heart failure. A selective MR modulator that antagonizes MR signaling in the heart but not the kidney would provide the cardiovascular protection of current MR antagonists but allow for normal electrolyte balance. The development of such a pharmaceutical requires an understanding of coregulators and their tissue-selective interactions with the MR, which is currently limited by the small repertoire of MR coregulators described in the literature. To identify potential novel MR coregulators, we used T7 phage display to screen tissue-selective cDNA libraries for MR-interacting proteins. Thirty MR binding peptides were identified, from which three were chosen for further characterization based on their nuclear localization and their interaction with other MR-interacting proteins or, in the case of x-ray repair cross-complementing protein 6, its known status as an androgen receptor coregulator. Eukaryotic elongation factor 1A1, structure-specific recognition protein 1, and x-ray repair cross-complementing protein 6 modulated MR-mediated transcription in a ligand-, cell- and/or promoter-specific manner and colocalized with the MR upon agonist treatment when imaged using immunofluorescence microscopy. These results highlight the utility of phage display for rapid and sensitive screening of MR binding proteins and suggest that eukaryotic elongation factor 1A1, structure-specific recognition protein 1, and x-ray repair cross-complementing protein 6 may be potential MR coactivators whose activity is dependent on the ligand, cellular context, and target gene promoter.

Duke Scholars

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Published In

Mol Endocrinol

DOI

EISSN

1944-9917

Publication Date

September 2014

Volume

28

Issue

9

Start / End Page

1571 / 1584

Location

United States

Related Subject Headings

  • Transcriptional Elongation Factors
  • Transcriptional Activation
  • Transcription, Genetic
  • Receptors, Mineralocorticoid
  • Receptors, Androgen
  • Peptide Library
  • Peptide Elongation Factor 1
  • Microscopy, Fluorescence
  • Ligands
  • Ku Autoantigen
 

Citation

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Yang, J., Fuller, P. J., Morgan, J., Shibata, H., McDonnell, D. P., Clyne, C. D., & Young, M. J. (2014). Use of phage display to identify novel mineralocorticoid receptor-interacting proteins. Mol Endocrinol, 28(9), 1571–1584. https://doi.org/10.1210/me.2014-1101
Yang, Jun, Peter J. Fuller, James Morgan, Hirotaka Shibata, Donald P. McDonnell, Colin D. Clyne, and Morag J. Young. “Use of phage display to identify novel mineralocorticoid receptor-interacting proteins.Mol Endocrinol 28, no. 9 (September 2014): 1571–84. https://doi.org/10.1210/me.2014-1101.
Yang J, Fuller PJ, Morgan J, Shibata H, McDonnell DP, Clyne CD, et al. Use of phage display to identify novel mineralocorticoid receptor-interacting proteins. Mol Endocrinol. 2014 Sep;28(9):1571–84.
Yang, Jun, et al. “Use of phage display to identify novel mineralocorticoid receptor-interacting proteins.Mol Endocrinol, vol. 28, no. 9, Sept. 2014, pp. 1571–84. Pubmed, doi:10.1210/me.2014-1101.
Yang J, Fuller PJ, Morgan J, Shibata H, McDonnell DP, Clyne CD, Young MJ. Use of phage display to identify novel mineralocorticoid receptor-interacting proteins. Mol Endocrinol. 2014 Sep;28(9):1571–1584.

Published In

Mol Endocrinol

DOI

EISSN

1944-9917

Publication Date

September 2014

Volume

28

Issue

9

Start / End Page

1571 / 1584

Location

United States

Related Subject Headings

  • Transcriptional Elongation Factors
  • Transcriptional Activation
  • Transcription, Genetic
  • Receptors, Mineralocorticoid
  • Receptors, Androgen
  • Peptide Library
  • Peptide Elongation Factor 1
  • Microscopy, Fluorescence
  • Ligands
  • Ku Autoantigen