A region in the steroid binding domain determines formation of the non-DNA-binding, 9 S glucocorticoid receptor complex.

This work was initiated to determine if a specific region of the glucocorticoid receptor determines the formation of the inactive (i.e. non-DNA-binding) 9 S form of the receptor recovered in cytosol preparations. It is known that the murine glucocorticoid receptor of the nti phenotype, which consists of only the carboxyl-terminal 40-kDa peptide containing the DNA-binding and steroid-binding domains separated by a short linker region, is recovered in hypotonic lysates as a 9 S heteromeric complex (Gehring, U., and Arndt, H. (1985) FEBS Lett. 179, 138-142). To further localize the domain required for formation of the 9 S complex, we have determined the sedimentation coefficients of receptors produced in COS-7 cells transfected with several mutants of the human glucocorticoid receptor gene. Deletion of the DNA-binding domain results in a 9 S complex that is somewhat less stable than the wild type receptor during sucrose gradient centrifugation. Deletion of the linker region yields a molybdate-stabilized 9 S complex, but deletion of the entire steroid-binding domain or internal deletion of the amino-terminal two-thirds of this domain yields receptors that are constitutive transcriptional activators and are present in cytosol only in the 4 S form. Taken together, these observations demonstrate that the steroid-binding domain contains the features required for formation of the 9 S heteromeric complex, and they are consistent with the proposal that the steroid-binding domain normally represses receptor function.

• Publication year

  1988

• Venue

  Journal of Biological Chemistry

• Publication date

  1988-01-05

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/s0021-9258(19)57388-4PMID 3335498
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Colocalization of DNA-binding and transcriptional activation functions in the human glucocorticoid receptor.

  1987cited by this paper
• Relationship of the 90-kDa murine heat shock protein to the untransformed and transformed states of the L cell glucocorticoid receptor.

  1987cited by this paper
• Structural organization and regulation of the chicken estrogen receptor.

  1987cited by this paper
• Cloning of human mineralocorticoid receptor complementary DNA: structural and functional kinship with the glucocorticoid receptor.

  1987cited by this paper
• Transformation of glucocorticoid and progesterone receptors to the DNA‐binding state

  1987cited by this paper
• Complete amino acid sequence of the human progesterone receptor deduced from cloned cDNA.

  1987cited by this paper
• The chicken oestrogen receptor sequence: homology with v‐erbA and the human oestrogen and glucocorticoid receptors.

  1986cited by this paper
• The possible role of disulfide bond reduction in transformation of the 10 S androgen receptor.

  1986cited by this paper
• Potential metal-binding domains in nucleic acid binding proteins.

  1986cited by this paper
• Sequence and expression of human estrogen receptor complementary DNA.

  1986cited by this paper
• Cloning and sequence analysis of rabbit progesterone-receptor complementary DNA.

  1986cited by this paper
• The mouse glucocorticoid receptor: mapping of functional domains by cloning, sequencing and expression of wild‐type and mutant receptor proteins.

  1986cited by this paper
• Molybdate-stabilized nonactivated glucocorticoid-receptor complexes contain a 90-kDa non-steroid-binding phosphoprotein that is lost on activation.

  1986cited by this paper
• Genetic complementation of a glucocorticoid receptor deficiency by expression of cloned receptor cDNA.

  1986cited by this paper
• Functional domains of the human glucocorticoid receptor.

  1986cited by this paper
• Heteromeric nature of glucocorticoid receptor

  1985cited by this paper
• Primary structure and expression of a functional human glucocorticoid receptor cDNA

  1985cited by this paper
• The heat shock response.

  1985cited by this paper
• Evidence that the 90-kDa phosphoprotein associated with the untransformed L-cell glucocorticoid receptor is a murine heat shock protein.

  1985cited by this paper
• Molybdate-stabilized glucocorticoid receptor: evidence for a receptor heteromer.

  1985cited by this paper
• A 90,000-dalton binding protein common to both steroid receptors and the Rous sarcoma virus transforming protein, pp60v-src.

  1985cited by this paper
• The molybdate-stabilized L-cell glucocorticoid receptor isolated by affinity chromatography or with a monoclonal antibody is associated with a 90-92-kDa nonsteroid-binding phosphoprotein.

  1985cited by this paper
• Isolation of steroid receptor binding protein from chicken oviduct and production of monoclonal antibodies.

  1985cited by this paper
• The common 90‐kd protein component of non‐transformed ‘8S’ steroid receptors is a heat‐shock protein.

  1985cited by this paper
• Effects of molybdate and endogenous inhibitors on steroid-receptor inactivation, transformation, and translocation.

  1984cited by this paper
• Common non-hormone binding component in non-transformed chick oviduct receptors of four steroid hormones

  1984cited by this paper
• Structure of mammalian steroid receptors: evolving concepts and methodological developments.

  1984cited by this paper
• Characterization of nonactivated and activated glucocorticoid-receptor complexes from intact rat thymus cells.

  1983cited by this paper
• Photoaffinity labeling and partial proteolysis of wild-type and variant glucocorticoid receptors.

  1983cited by this paper
• Structure, dissociation, and proteolysis of mammalian steroid receptors. Multiplicity of glucocorticoid receptor forms and proteolytic enzymes in rat liver and kidney cytosols.

  1983cited by this paper
• Subunit dissociation as a possible mechanism of glucocorticoid receptor activation.

  1983cited by this paper
• Efficient infection of monkey cells with DNA of simian virus 40.

  1981cited by this paper
• SV40-transformed simian cells support the replication of early SV40 mutants.

  1981cited by this paper

• Mechanisms of erythrocyte development and regeneration: implications for regenerative medicine and beyond

  2018cites this paper
• Biological relevance of Hsp90‐binding immunophilins in cancer development and treatment

  2016cites this paper
• Deep Insight Section

  2012influential citation
• Conserved Steroid Hormone Homology Converges on Nuclear Factor κB to Modulate Inflammation in Asthma

  2012cites this paper
• Mapping of Structure-Function Peptide Sites on the Human Alpha-fetoprotein Amino Acid Sequence

  2011cites this paper
• A unique mechanism of chaperone action: heme regulation of Hap1 activity involves separate control of repression and activation.

  2009cites this paper
• Targeted ablation reveals a novel role of FKBP52 in gene-specific regulation of glucocorticoid receptor transcriptional activity.

  2009cites this paper
• Anomalies in the Endocrine Axes of the Guinea Pig: Relevance to Human Physiology and Disease*

  2008cites this paper
• Role of estrogen receptor beta in epithelia lacking estrogen receptor alpha expression

  2008cites this paper
• Biological functions and clinical implications of oestrogen receptors alfa and beta in epithelial tissues

  2008cites this paper
• Minireview: the intersection of steroid receptors with molecular chaperones: observations and questions.

  2008cites this paper
• Control of glucocorticoid and progesterone receptor subcellular localization by the ligand-binding domain is mediated by distinct interactions with tetratricopeptide repeat proteins.

  2008cites this paper
• Regulation of anti-oxidant and anti-apoptotic genes by progesterone in cardiomyocytes

  2007cites this paper
• A conformational switch in the ligand-binding domain regulates the dependence of the glucocorticoid receptor on Hsp90.

  2007cites this paper
• Intracellular r e c e ~ t o r s use a common mechanism to interpret signaling information at response elements

  2007cites this paper
• Differential regulation of glucocorticoid and progesterone receptor subcellular localization by tetratricopeptide repeat domain proteins

  2007cites this paper
• The Mr ~ 90,000 Heat Shock Protein: An Important Modulator of Ligand and DNA-binding Properties of the Glucocorticoid Receptor1

  2006influential citation
• Chaperoning of glucocorticoid receptors.

  2006cites this paper
• Nuclear receptor functions in the central nervous system : Clues from knockout mice

  2006cites this paper
• An investigation of the role of phosphorylation at Ser211 of the glucocorticoid receptor in ligand-specific transcriptional regulation

  2005cites this paper
• The search for safer glucocorticoid receptor ligands.

  2005cites this paper
• [Estrogen receptor Beta isoforms -- functions and clinical relevance in breast cancer].

  2005cites this paper
• Reproductive tissue-selective actions of progesterone receptors.

  2005cites this paper
• Glucocorticoid receptor and heat shock factor 1: novel mechanism of reciprocal regulation.

  2005cites this paper
• Reproductive tissue selective actions of progesterone receptors.

  2004cites this paper
• Insights into the molecular biology of the estrogen receptor define novel therapeutic targets for breast cancer.

  2004cites this paper
• Progesterone-dependent regulation of female reproductive activity by two distinct progesterone receptor isoforms.

  2003cites this paper
• An investigation of the interactions of the androgen receptor with a non-steroidal compound and two synthetic progestins

  2002cites this paper
• Steroid Receptor and Enzyme Abnormalities ANDROGEN RECEPTOR ABNORMALITIES

  2002cites this paper
• Mutations at Positions 547–553 of Rat Glucocorticoid Receptors Reveal That hsp90 Binding Requires the Presence, but Not Defined Composition, of a Seven-amino Acid Sequence at the Amino Terminus of the Ligand Binding Domain*

  2002cites this paper
• Human alpha-fetoprotein contains potential heterodimerization motifs capable of interaction with nuclear receptors and transcription/growth factors.

  2002cites this paper
• Do Not Bind 17P-Estradiol Dimerize and Bind to the Estrogen Response Element in Viva

  2001cites this paper
• The Nuclear Receptor Superfamily

  2001cites this paper
• Cellular Responses to Hormones

  2001cites this paper
• PDFlib PLOP: PDF Linearization, Optimization, Protection Page inserted by evaluation version

  2001cites this paper
• Subnuclear Trafficking of Glucocorticoid Receptors

  2000cites this paper
• Progesterone receptors in reproduction: functional impact of the A and B isoforms.

  2000cites this paper
• Reproductive Functions of the Progesterone Receptor

  2000cites this paper
• Reproductive functions of the progesterone receptor.

  2000cites this paper
• The molecular chaperone Hsp90 can negatively regulate the activity of a glucocorticosteroid-dependent promoter.

  1999cites this paper
• Delimitation of two regions in the 90-kDa heat shock protein (Hsp90) able to interact with the glucocorticosteroid receptor (GR).

  1999cites this paper
• Charakterisierung putativer Cofaktoren der Progesteron-Rezeptor vermittelten Transaktivierung

  1999cites this paper
• The androgen receptor: Physiology and pathophysiology

  1998cites this paper
• Binding of hsp90 to the Glucocorticoid Receptor Requires a Specific 7-Amino Acid Sequence at the Amino Terminus of the Hormone-binding Domain*

  1998cites this paper
• Review¶Hormone action and chromatin remodelling

  1998cites this paper
• Molecular Biology of the Endothelin Receptors

  1998cites this paper
• P2 Receptor Modeling and Identification of Ligand Binding Sites

  1998cites this paper
• Molecular chaperones: biology and prospects for pharmacological intervention.

  1998cites this paper
• The Vitamin D Receptor: Discovery, Structure, and Function

  1998cites this paper
• Mechanisms of progesterone receptor export from nuclei: role of nuclear localization signal, nuclear export signal, and ran guanosine triphosphate.

  1998cites this paper
• Hormone action and chromatin remodelling.

  1998cites this paper
• A Conserved Proline in the hsp90 Binding Region of the Glucocorticoid Receptor Is Required for hsp90 Heterocomplex Stabilization and Receptor Signaling*

  1998cites this paper
• A role for HDJ-2/HSDJ in correcting subnuclear trafficking, transactivation, and transrepression defects of a glucocorticoid receptor zinc finger mutant.

  1997cites this paper
• Two populations of the estrogen receptor separated and characterized using aqueous two-phase partitioning.

  1997cites this paper
• Steroid Hormone Receptor Families

  1997cites this paper
• The role of the hsp90-based chaperone system in signal transduction by nuclear receptors and receptors signaling via MAP kinase.

  1997cites this paper
• Disruption of the glucocorticoid receptor assembly with heat shock protein 90 by a peptidic antiglucocorticoid.

  1997cites this paper
• Steroid receptor interactions with heat shock protein and immunophilin chaperones.

  1997cites this paper
• Human mineralocorticoid receptor interacts with actin under mineralocorticoid ligand modulation

  1996cites this paper
• Two eukaryote-specific regions of Hsp82 are dispensable for its viability and signal transduction functions in yeast.

  1996cites this paper
• Ligands for orphan receptors?

  1996cites this paper
• Intracellular receptors use a common mechanism to interpret signaling information at response elements.

  1996cites this paper
• Ability of various members of the hsp70 family of chaperones to promote assembly of the glucocorticoid receptor into a functional heterocomplex with hsp90.

  1996cites this paper
• In vivo evidence for the generation of a glucocorticoid receptor-heat shock protein-90 complex incapable of binding hormone by the calmodulin antagonist phenoxybenzamine.

  1996cites this paper
• The peroxisome proliferator activated receptors (PPARS) and their effects on lipid metabolism and adipocyte differentiation.

  1996cites this paper
• Antidepressants and hypothalamic-pituitary-adrenocortical regulation.

  1996cites this paper
• Control of Transcription by Steroid Hormones a

  1996cites this paper
• Assessment of glucocorticoid receptor-heat shock protein 90 interactions in vivo during nucleocytoplasmic trafficking.

  1996cites this paper
• Anomalies in the endocrine axes of the guinea pig: relevance to human physiology and disease.

  1996cites this paper
• [Receptor mechanisms of glucocorticoid and antiglucocorticoid effects].

  1996cites this paper
• Delayed glucocorticoid-dependent development of the insulin response after heat shock in cultured fetal hepatocytes: correlation with a transient defect in glucocorticoid receptor binding property.

  1996cites this paper
• Use of the Thiol-specific Derivatizing Agent N-Iodoacetyl-3-Iiodotyrosine to Demonstrate Conformational Differences between the Unbound and hsp90-bound Glucocorticoid Receptor Hormone Binding Domain (*)

  1996cites this paper
• Retinoic Acid Receptors

  1995cites this paper
• Hormone-independent repression of AP-1-inducible collagenase promoter activity by glucocorticoid receptors

  1995cites this paper
• The Glucocorticoid Hormone Receptor

  1995cites this paper
• A Study of Differences in Binding of Hepatic Nuclear Proteins to the Upstream Region of Glucocorticoid Regulated Tyrosine Aminotransferase Gene in Lean and Obese Rats.

  1995cites this paper
• Immunocytochemical analysis of hormone mediated nuclear translocation of wild type and mutant glucocorticoid receptors.

  1995cites this paper
• Androgen receptor defects : Historical, clinical, and molecular perspectives

  1995cites this paper
• Synthetic peptides derived from the steroid binding domain block modulator and molybdate action toward the rat glucocorticoid receptor.

  1995cites this paper
• Electron transfer between cytochromec and cytochromec peroxidase

  1995cites this paper
• Androgen receptor defects: historical, clinical, and molecular perspectives.

  1995cites this paper
• Cysteines 638 and 665 in the hormone binding domain of human glucocorticoid receptor define the specificity to glucocorticoids.

  1995cites this paper
• Distinct functions of the 90 kDa heat-shock protein (hsp90) in oestrogen and mineralocorticosteroid receptor activity: effects of hsp90 deletion mutants.

  1995cites this paper
• Transcription factors 3: nuclear receptors.

  1995cites this paper
• Signalling Mechanisms — from Transcription Factors to Oxidative Stress

  1995cites this paper
• Functional Analysis of the Glucocorticoid Receptor

  1995cites this paper
• Platelet-derived Growth Factor Signal Transduction through the Interferon-inducible Kinase PKR

  1995cites this paper
• Some new aspects of molecular mechanisms of cyclosporin A effect on immune response

  1995cites this paper
• Estrogen receptor mutants which do not bind 17 beta-estradiol dimerize and bind to the estrogen response element in vivo.

  1995cites this paper
• Inducible Gene Expression, Volume 2

  1995cites this paper
• Structural and Functional Studies of Selective DNA Binding by Steroid/Nuclear Receptors

  1994cites this paper
• Hormone binding domain of human glucocorticoid receptor. Enhancement of transactivation function by substitution mutants M565R and A573Q.

  1994cites this paper
• The quaternary structures of untransformed steroid hormone receptors: an open issue.

  1994cites this paper
• Heat Shock Proteins and the Cytoplasmic-Nuclear Trafficking of Steroid Receptors

  1994cites this paper
• The Functional Relevance of the Heteromeric Structure of Corticosteroid Receptors a

  1994cites this paper
• Selective deletions in the 90 kDa heat shock protein (hsp90) impede hetero-oligomeric complex formation with the glucocorticosteroid receptor (GR) or hormone binding by GR.

  1994cites this paper
• Glucocorticoid receptors and resistance to glucocorticoids in hematologic malignancies.

  1994cites this paper
• Function/activity of specific amino acids in glucocorticoid receptors.

  1994cites this paper
• Molecular mechanisms of action of steroid/thyroid receptor superfamily members.

  1994cites this paper
• The C-terminal region of the vitamin D receptor is essential to form a complex with a receptor auxiliary factor required for high affinity binding to the vitamin D-responsive element.

  1994cites this paper