Separable features of the ligand-binding domain determine the differential subcellular localization and ligand-binding specificity of glucocorticoid receptor and progesterone receptor

Yihong Wan, Kimberly K. Coxe, Varykina G. Thackray, Paul R. Housley, Steven K. Nordeen

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Glucocorticoid receptor (GR) and progesterone receptor (PR) are closely related members of the steroid receptor family of transcription factors. The two receptors share a similar domain structure, substantial sequence identity, DNA binding specificity, and the ability to induce many of the same genes. Despite these similarities, the unliganded GR is localized predominantly in the cytoplasm, while unliganded PR is found predominantly in the nucleus. By expressing green fluorescent protein (GFP)-tagged receptors and assessing subcellular localization in living cells by confocal microscopy, we have investigated the structural basis for the differential localization of GR and PR. By constructing a series of GFP-tagged receptor chimeras between GR and PR, we have shown that multiple features in the N-terminal half of the ligand-binding domain (LBD) are the critical determinants that mandate the differential localization of GR and PR. Replacement of residues encompassing helices 1-5 of GR with those of PR yields a receptor that is nuclear. However, this domain is unable to mediate nuclear import by itself when removed from the context of the receptor. The chimeric receptors also indicate that regions encompassing helices 6 and 7 are key determinants of the ligand binding potential and the transactivation potential of receptors. Thus, the determinants specifying localization of hormone-free receptors are separable from those governing ligand binding character.

Original languageEnglish (US)
Pages (from-to)17-31
Number of pages15
JournalMolecular Endocrinology
Volume15
Issue number1
DOIs
StatePublished - 2001

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Glucocorticoid Receptors
Progesterone Receptors
Ligands
Green Fluorescent Proteins
Cell Nucleus Active Transport
Steroid Receptors
Cytoplasmic and Nuclear Receptors
Confocal Microscopy
Transcriptional Activation
Cytoplasm
Transcription Factors
Hormones
Genes

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

Separable features of the ligand-binding domain determine the differential subcellular localization and ligand-binding specificity of glucocorticoid receptor and progesterone receptor. / Wan, Yihong; Coxe, Kimberly K.; Thackray, Varykina G.; Housley, Paul R.; Nordeen, Steven K.

In: Molecular Endocrinology, Vol. 15, No. 1, 2001, p. 17-31.

Research output: Contribution to journalArticle

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