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PMID: 2100202 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Signal transduction by steroid hormones: nuclear localization is differentially regulated in estrogen and glucocorticoid receptors.

Cell regulation ·Vol. 1 ·No. 3 ·1990-02-00 ·Pages 291-9

Picard D, Kumar V, Chambon P, Yamamoto KR

Abstract

The glucocorticoid receptor accumulates in nuclei only in the presence of bound hormone, whereas the estrogen receptor has been reported to be constitutively nuclear. To investigate this distinction, we compared the nuclear localization domains of the two receptors and the capacity of their respective hormone-binding regions to regulate nuclear localization activity. As with the glucocorticoid receptor, we showed that the human estrogen receptor contained a nuclear localization signal between the DNA-binding and hormone-binding regions (amino acids 256-303); however, in contrast to the glucocorticoid receptor, the estrogen receptor lacked a second nuclear localization domain within the hormone-binding region. Moreover, the hormone-binding domain of the unliganded estrogen receptor failed to regulate nuclear localization signals, although it efficiently regulated other receptor functions. We conclude that the two receptors employ a common mechanism for signal transduction involving a novel "inactivation" function, but that they differ in their control of nuclear localization. Thus, despite the strong relatedness of the estrogen and glucocorticoid receptors in structure and activity, certain differences in their properties could have important functional implications.

MeSH Terms
Amino Acid Sequence Animals Base Sequence Cell Nucleus/metabolism Cells, Cultured Chlorocebus aethiops DNA-Binding Proteins/metabolism Glucocorticoids/physiology Models, Biological Molecular Sequence Data Receptors, Estrogen/metabolism Receptors, Glucocorticoid/metabolism Recombinant Fusion Proteins/metabolism Signal Transduction Steroids/physiology
Chemicals
DNA-Binding Proteins Glucocorticoids Receptors, Estrogen Receptors, Glucocorticoid Recombinant Fusion Proteins Steroids
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Picard D
Department of Biochemistry and Biophysics, University of California, San Francisco 94143-0448.
Kumar V
Chambon P
Yamamoto K R
References (51)
51 references, click to expand
  1. Monoclonal antibodies localize oestrogen receptor in the nuclei of target cells.
    Nature. 1984 Feb 23-29;307(5953):745-7 PMID: 6700704
  2. Hormone-mediated repression: a negative glucocorticoid response element from the bovine prolactin gene.
    Genes Dev. 1988 Sep;2(9):1144-54 PMID: 3192076
  3. Monoclonal antibodies against the rat liver glucocorticoid receptor.
    Proc Natl Acad Sci U S A. 1984 Mar;81(6):1609-13 PMID: 6200880
  4. Heteromeric nature of glucocorticoid receptors.
    FEBS Lett. 1985 Jan 1;179(1):138-42 PMID: 3965298
  5. Immunocytochemical study of mammalian progesterone receptor using monoclonal antibodies.
    Endocrinology. 1985 Apr;116(4):1473-84 PMID: 3971924
  6. Nuclear localization of unoccupied receptors for glucocorticoids, estrogens, and progesterone in GH3 cells.
    Endocrinology. 1985 Nov;117(5):2140-7 PMID: 4042978
  7. Evidence that the 90-kDa phosphoprotein associated with the untransformed L-cell glucocorticoid receptor is a murine heat shock protein.
    J Biol Chem. 1985 Oct 15;260(23):12398-401 PMID: 3900074
  8. A 90,000-dalton binding protein common to both steroid receptors and the Rous sarcoma virus transforming protein, pp60v-src.
    J Biol Chem. 1985 Nov 15;260(26):14292-6 PMID: 2414293
  9. Sequence and expression of human estrogen receptor complementary DNA.
    Science. 1986 Mar 7;231(4742):1150-4 PMID: 3753802
  10. The lysosome as a mediator of hormone action.
    Recent Prog Horm Res. 1974;30(0):171-233 PMID: 4367107
  11. Protein migration into nuclei. I. Frog oocyte nuclei in vivo accumulate microinjected histones, allow entry to small proteins, and exclude large proteins.
    J Cell Biol. 1975 Feb;64(2):421-30 PMID: 46868
  12. Nuclear envelope permeability.
    Nature. 1975 Mar 13;254(5496):109-14 PMID: 1117994
  13. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells.
    Mol Cell Biol. 1982 Sep;2(9):1044-51 PMID: 6960240
  14. Easy identification of cDNA clones.
    EMBO J. 1983;2(10):1791-4 PMID: 6315402
  15. The common 90-kd protein component of non-transformed '8S' steroid receptors is a heat-shock protein.
    EMBO J. 1985 Dec 1;4(12):3131-5 PMID: 2419124
  16. Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-A.
    Nature. 1986 Mar 13-19;320(6058):134-9 PMID: 3754034
  17. Molecular mobility and nucleocytoplasmic flux in hepatoma cells.
    J Cell Biol. 1986 Apr;102(4):1183-90 PMID: 2420804
  18. Ultrastructural localization of the progesterone receptor by an immunogold method: effect of hormone administration.
    J Cell Biol. 1986 Apr;102(4):1191-9 PMID: 3958043
  19. Phenol red in tissue culture media is a weak estrogen: implications concerning the study of estrogen-responsive cells in culture.
    Proc Natl Acad Sci U S A. 1986 Apr;83(8):2496-500 PMID: 3458212
  20. The chicken oestrogen receptor sequence: homology with v-erbA and the human oestrogen and glucocorticoid receptors.
    EMBO J. 1986 May;5(5):891-7 PMID: 3755102
  21. Localisation of the oestradiol-binding and putative DNA-binding domains of the human oestrogen receptor.
    EMBO J. 1986 Sep;5(9):2231-6 PMID: 3780678
  22. Glucocorticoid receptor mutants that are constitutive activators of transcriptional enhancement.
    Nature. 1987 Jan 22-28;325(6102):365-8 PMID: 3808033
  23. Molecular cloning and characterization of rat estrogen receptor cDNA.
    Nucleic Acids Res. 1987 Mar 25;15(6):2499-513 PMID: 3031601
  24. Relationship of the 90-kDa murine heat shock protein to the untransformed and transformed states of the L cell glucocorticoid receptor.
    J Biol Chem. 1987 May 25;262(15):6986-91 PMID: 3294824
  25. The effect of protein context on nuclear location signal function.
    Cell. 1987 Jul 31;50(3):465-75 PMID: 3038333
  26. Functional domains of the human estrogen receptor.
    Cell. 1987 Dec 24;51(6):941-51 PMID: 3690665
  27. A region in the steroid binding domain determines formation of the non-DNA-binding, 9 S glucocorticoid receptor complex.
    J Biol Chem. 1988 Jan 5;263(1):267-73 PMID: 3335498
  28. Two signals mediate hormone-dependent nuclear localization of the glucocorticoid receptor.
    EMBO J. 1987 Nov;6(11):3333-40 PMID: 3123217
  29. Specific synthesis of DNA in vitro via a polymerase-catalyzed chain reaction.
    Methods Enzymol. 1987;155:335-50 PMID: 3431465
  30. Interaction of the Mr = 90,000 heat shock protein with the steroid-binding domain of the glucocorticoid receptor.
    J Biol Chem. 1988 Dec 5;263(34):18520-3 PMID: 3192546
  31. Steroid hormone-dependent interaction of human progesterone receptor with its target enhancer element.
    Mol Endocrinol. 1988 Dec;2(12):1221-9 PMID: 3216861
  32. Evidence that the 90-kDa heat shock protein is necessary for the steroid binding conformation of the L cell glucocorticoid receptor.
    J Biol Chem. 1989 Mar 25;264(9):4992-7 PMID: 2647745
  33. Nuclear receptors enhance our understanding of transcription regulation.
    Trends Genet. 1988 Nov;4(11):309-14 PMID: 2853466
  34. The heat-shock proteins.
    Annu Rev Genet. 1988;22:631-77 PMID: 2853609
  35. Context affects nuclear protein localization in Saccharomyces cerevisiae.
    Mol Cell Biol. 1989 Feb;9(2):384-9 PMID: 2496300
  36. Mineralocorticosteroid receptor of the chick intestine. Oligomeric structure and transformation.
    J Biol Chem. 1989 Jun 5;264(16):9304-9 PMID: 2542305
  37. Protein encoded by v-erbA functions as a thyroid-hormone receptor antagonist.
    Nature. 1989 Jun 22;339(6226):593-7 PMID: 2733791
  38. Mechanisms of nuclear localization of the progesterone receptor: evidence for interaction between monomers.
    Cell. 1989 Jun 30;57(7):1147-54 PMID: 2736623
  39. Chimaeras of myc oncoprotein and steroid receptors cause hormone-dependent transformation of cells.
    Nature. 1989 Jul 6;340(6228):66-8 PMID: 2662015
  40. Ligand-regulated nonspecific inactivation of receptor function: a versatile mechanism for signal transduction.
    Cold Spring Harb Symp Quant Biol. 1988;53 Pt 2:803-11 PMID: 3076098
  41. Nuclear protein transport.
    Crit Rev Biochem Mol Biol. 1989;24(4):419-35 PMID: 2670452
  42. The cloned human oestrogen receptor contains a mutation which alters its hormone binding properties.
    EMBO J. 1989 Jul;8(7):1981-6 PMID: 2792078
  43. Steroid receptors. How to be both a receptor and a transcription factor.
    Biochem Pharmacol. 1989 Oct 1;38(19):3135-43 PMID: 2684163
  44. Polypeptide chain binding proteins: catalysts of protein folding and related processes in cells.
    Cell. 1989 Nov 17;59(4):591-601 PMID: 2573430
  45. Structural organization and expression of the mouse estrogen receptor.
    Mol Endocrinol. 1987 Oct;1(10):735-44 PMID: 2484714
  46. Evidence for intracellular association of the glucocorticoid receptor with the 90-kDa heat shock protein.
    J Biol Chem. 1988 Mar 5;263(7):3474-81 PMID: 3277971
  47. The steroid and thyroid hormone receptor superfamily.
    Science. 1988 May 13;240(4854):889-95 PMID: 3283939
  48. A movable and regulable inactivation function within the steroid binding domain of the glucocorticoid receptor.
    Cell. 1988 Sep 23;54(7):1073-80 PMID: 2843290
  49. Association of the Ah receptor with the 90-kDa heat shock protein.
    J Biol Chem. 1988 Sep 25;263(27):13802-5 PMID: 2843537
  50. The estrogen receptor binds tightly to its responsive element as a ligand-induced homodimer.
    Cell. 1988 Oct 7;55(1):145-56 PMID: 3167974
  51. Nuclear localization of unoccupied oestrogen receptors.
    Nature. 1984 Feb 23-29;307(5953):747-9 PMID: 6700705
Article Info
Journal
Cell regulation
Abbr.
Cell Regul
ISSN
1044-2030
Published
1990-02-00
Pages
291-9
Language
English
Region
United States
NLM ID
9005331
PMCID
PMC361473
Subset
IM
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