Рецептор глюкокортикоидов: переход из цитоплазмы в клеточное ядро, хроматиновый и внутриядерный шапероновый циклы


https://doi.org/10.18699/VJ15.032

Полный текст:


Аннотация

Рецептор глюкокортикоидных гормонов (ГР) является лигандзависимым фактором транскрипции, регулирующим экспрессию сотен генов. В отсутствие гормона ГР находится в цитоплазме клетки в комплексе c молекулярными шаперонами hsp90, hsp70, p23, Hop, FKBP51, FKBP52 и др. В составе этого комплекса ГР приобретает конформацию, обладающую высоким сродством к глюкокортикоидам. После связывания с гормоном рецептор высвобождается из комплекса с шаперонами и переходит в клеточное ядро, где взаимодействует со специфическими участками ДНК (GREs) генов-мишеней глюкокортикоидов, влияя на интенсивность их транскрипции. Затем свободный от гормона ГР выходит из клеточного ядра в цитоплазму, завершая ядерно-цитоплазматический цикл этого белка. Согласно современным представлениям, существуют также внутриядерные хроматиновый и шапероновый циклы ГР. Хроматиновым циклом называется цикл связывания/диссоциации/повторного связывания гормонрецепторных комплексов с GREs, занимающий от нескольких секунд до нескольких десятков секунд. Шапероновый цикл происходит после диссоциации гормон-рецепторного комплекса в ядрах, когда ГР связывается с присутствующими в них теми же молекулярными шаперонами, которые взаимодействуют с этим белком в цитоплазме, и в результате чего вновь связывает гормон, затем высвобождается из комплекса с шаперонами и снова взаимодействует с GREs. Предполагается, что главным образом за счет существования шаперонового цикла ГР удерживается в ядре клетки в течение нескольких часов. В настоящем обзоре обобщены имеющиеся в литературе данные, на основании которых были построены модели хроматинового и внутриядерного шаперонового циклов ГР и проведен их критический анализ.


Об авторах

В. М. Меркулов
Федеральное государственное бюджетное научное учреждение «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук», Новосибирск, Россия
Россия


Н. В. Климова
Федеральное государственное бюджетное научное учреждение «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук», Новосибирск, Россия
Россия


Т. И. Меркулова
Федеральное государственное бюджетное научное учреждение «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук», Новосибирск, Россия
Россия


Список литературы

1. А.Н. Ядерные рецепторы: номенклатура, лиганды, механизмы влияния на экспрессию генов. Биохимия. 2002;67:1157-1181.

2. Archer T.K., Cordingley M.G., Wolford R.G., Hager G.L. Transcription factor access is mediated by accurately positioned nucleosomes on the mouse mammary tumor virus promoter. Mol. Cell. Biol. 1991;11(2):688-698. DOI: 10.1128/MCB.11.2.688

3. Baxter J.D., Tomkins G.M. Specific cytoplasmic glucocorticoid hormone receptors in hepatoma tissue culture cells. Proc. Natl Acad. Sci. USA. 1971;68(5):932-937.

4. Beato M., Chalepakis G., Schauer M., Slater E.P. DNA regulatory elements for steroid hormones. J. Steroid. Biochem. 1989;32(5):737-748. DOI: 10.1016/0022-4731(89)90521-9

5. Beato M., Kalimi M., Feigelson P. Correlation between glucocorticoid binding to specific liver cytosol receptors and enzyme induction in vivo. Biochem. Biophys. Res. Commun. 1972;47(6):1464-1472. DOI: 10.1016/0006-291X(72)90237-9

6. Beato M., Klug J. Steroid hormone receptors: an update. Hum. Reprod. Update. 2000;6(3):225-236. DOI: 10.1093/humupd/6.3.225

7. Black B.E., Holaska J.M., Rastinejad F., Paschal B.M. DNA binding domains in diverse nuclear receptors function as nuclear export signals. Curr. Biol. 2001;11(22):1749-1758. DOI: 10.1016/S0960-9822(01)00537-1

8. Bosisio D., Marazzi I., Agresti A., Shimizu N., Bianchi M.E., Natoli G. A hyper-dynamic equilibrium between promoter-bound and nucleoplasmic dimers controls NF-kB-dependent gene activity. EMBO J. 2006;25(4):798-810. DOI 10.1038/sj.emboj.7600977

9. Boumpas D.T., Chrousos G.P., Wilder R.L., Cupps T.R., Balow J.E. Glucocorticoid therapy for immune-mediated diseases: basic and clinical correlates. Ann. Intern. Med. 1993;119(12):1198-1208. DOI: 10.7326/0003-4819-119-12-199312150-00007

10. Bresnick E.H., Dalman F.C., Sanchez E.R., Pratt W.B. 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;264(9):4992-4997.

11. Carey K.L., Richards S.A., Lounsbury K.M., Macara I.G. Evidence using a green fluorescent protein-glucocorticoid receptor chimera that the Ran/TC4 GTPase mediates an essential function independent of nuclear protein import. J. Cell. Biol. 1996;133(5):985-996. DOI: 10.1083/jcb.133.5.985

12. Cheung J., Smith D.F. Molecular shaperone interactions with steroid receptors: an update. Mol. Endocrinol. 2000;14(7):939-946. DOI: 10.1210/me.14.7.939

13. Conway-Campbell B.L., McKenna M.A., Wiles C.C., Atkinson H.C., de Kloet E.R., Lightman S.L. Proteasome-dependent down-regulation of activated nuclear hippocampal glucocorticoid receptors determines dynamicresponses to corticosterone. Endocrinology. 2007;148(11):5470-5547. DOI: 10.1210/en.2007-0585

14. Conway-Campbell B.L., Pooley J.R., Hager G.L., Lightman S.L. Molecular dynamics of ultradian glucocorticoid receptor action. Mol. Cell Endocrinol. 2012;348(2):383-393. DOI: 10.1016/j.mce.2011.08.014

15. Conway-Campbell B.L., Sarabdjitsingh R.A., McKenna M.A., Pooley J.R., Kershaw Y.M., Meijer O.C., De Kloet E.R., Lightman S.L. Glucocorticoid ultradian rhythmicity directs cyclical gene pulsing of the clock gene period 1 in rat hippocampus. J. Neuroendocrinol. 2010;22(10):1093-100. DOI: 10.1111/j.1365-2826.2010.02051.x

16. Danielsen M., Northrop J.P., Ringold G.M. The mouse glucocorticoid receptor: mapping of functional domains by cloning, sequencing and expression of wild-type and mutant receptor proteins. EMBO J. 1986;5(10):2513-2522.

17. Daugaard M., Rohde M., Jäättelä M. The heat shock protein 70 family: Highly homologous proteins with overlapping and distinct functions. FEBS Lett. 2007;581(19):3702-3710. DOI: 10.1016/j.febslet. 2007.05.039

18. Davies T.H., Ning Y.M., Sánchez E.R. A new first step in activation of steroid receptors: hormone-induced switching of FKBP51 and FKBP52 immunophilins. J. Biol. Chem. 2002;277(7):4597-4600. DOI: 10.1074/jbc.C100531200

19. Drouin J., Sun Y.L., Tremblay S., Lavender P., Schmidt T.J., de Léan A., Nemer M. Homodimer formation is rate-limiting for high affinity DNA binding by glucocorticoid receptor. Mol. Endocrinol. 1992;6(8):1299-1309. DOI: 10.1210/me.6.8.1299

20. Echeverria P.C., Picard D. Molecular chaperones, essential partners of steroid hormone receptors for activity and mobility. Biochim. Biophys. Acta. 2010;1803(6):641-649. DOI: 10.1016/j.bbamcr.2009.11.012

21. Erlejman A.G., Lagadari M., Toneatto J., Piwien-Pilipuk G., Galigniana M.D. Regulatory role of the 90-kDa-heat-shock protein (Hsp90) and associated factors on gene expression. Biochim. Biophys. Acta. 2014;1839(2):71-87. DOI: 10.1016/j.bbagrm.2013.12.006

22. Fletcher T.M., Ryu B.W., Baumann C.T., Warren B.S., Fragoso G., John S., Hager G.L. Structure and dynamic properties of a glucocorticoid receptor-induced chromatin transition. Mol. Cell. Biol. 2000;20(17):6466-6475. DOI: 10.1128/MCB.20.17.6466-6475.2000

23. Fletcher T.M., Xiao N., Mautino G., Baumann C.T., Wolford R., Warren B.S., Hager G.L. ATP-dependent mobilization of the glucocorticoid receptor during chromatin remodeling. Mol. Cell. Biol. 2002; 22(10):3255-3263. DOI: 10.1128/MCB.22.10.3255-3263.2002

24. Freeman B.C., Yamamoto K.R. Disassembly of transcriptional regulatory complexes by molecular chaperones. Science. 2002;296(5576): 2232-2235. DOI:10.1126/science.1073051

25. Freedman N.D., Yamamoto K.R. Importin 7 and Importin {alpha}/Importin {beta}Are Nuclear Import Receptors for the Glucocorticoid Receptor. Mol. Biol. Cell. 2004;15(5):2276-3386. DOI: 10.1091/mbc.E03-11-0839

26. Gametchu B., Harrison R.W. Characterization of a monoclonal antibody to the rat liver glucocorticoid receptor. Endocrinology. 1984; 114(1):274-279. DOI: http://dx.doi.org/10.1210/endo-114-1-274

27. George A.A., Schiltz R.L., Hager G.L. Dynamic access of the glucocorticoid receptor to response elements in chromatin. Int. J. Biochem. Cell. Biol. 2009;41(1):214-224. DOI: 10.1016/j.biocel.2008.09.019

28. Grad I., Picard D. The glucocorticoid responses are shaped by molecular chaperones. Mol. Cell. Endocrinol. 2007;275(1/2):2-12. DOI: 10.1016/j.mce.2007.05.018

29. Grenert J.P., Johnson B.D., Toft D.O. The importance of ATP binding and hydrolysis by hsp90 in formation and function of protein heterocomplexes. J. Biol. Chem. 1999;274(25):17525-17533. DOI: 10.1074/jbc.274.25.17525

30. Haché R.J., Tse R., Reich T., Savory J.G., Lefebvre Y.A. Nucleocytoplasmic trafficking of steroid-free glucocorticoid receptor. J. Biol. Chem. 1999;274(3):1432-1439. DOI: 10.1074/jbc.274.3.1432

31. Hager G.L., Fletcher T.M., Xiao N., Baumann C.T., Müller W.G., McNally J.G. Dynamics of gene targeting and chromatin remodelling by nuclear receptors. Biochem. Soc. Trans. 2000;28(4):405-410. DOI: 10.1042/0300-5127:0280405

32. Harrell J.M., Murphy P.J., Morishima Y., Chen H., Mansfield J.F., Galigniana M.D., Pratt W.B. Evidence for glucocorticoid receptor transport on microtubules by dynein. J. Biol. Chem. 2004;279(52):54647-54654. DOI: 10.1074/jbc.M406863200

33. Hierholzer K., Buhler H. Metabolism of cortical steroid hormones and their general mode of action. Comprehensive human physiology. Ed. R. Greger, U. Windhorst. Berlin; Heidelberg: Springer-Verlag, 1996. DOI: 10.1007/978-3-642-60946-6_21

34. Higgins S.J., Rousseau G.G., Baxter J.D., Tomkins G.M. Early events in glucocorticoid action. Activation of the steroid receptor and its subsequent specific nuclear binding studied in a cell-free system. J. Biol. Chem. 1973;248(16):5866-5872.

35. Holaska J.M., Black B.E., Love D.C., Hanover J.A., Leszyk J., Paschal B.M. Calreticulin is a receptor for nuclear export. J. Cell Biol. 2001;152(1):127-140. DOI: 10.1083/jcb.152.1.127

36. Holaska J.M., Black B.E., Rastinejad F., Paschal B.M. Ca2+-dependent nuclear export mediated by calreticulin. Mol. Cell. Biol. 2002;22(17):6286-6297. DOI: 10.1128/MCB.22.17.6286-6297.2002

37. John S., Sabo P.J., Johnson T.A., Sung M.H., Biddie S.C., Lightman S.L., Voss T.C., Davis S.R., Meltzer P.S., Stamatoyannopoulos J.A., Hager G.L. Interaction of the glucocorticoid receptor with the global chromatin landscape. Mol. Cell. 2008;29(5):611-624. DOI: 10.1016/j.molcel.2008.02.010

38. John S., Sabo P.J., Thurman R.E., Sung M.H., Biddie S.C., Johnson T.A., Hager G.L., Stamatoyannopoulos J.A. Chromatin accessibility predetermines glucocorticoid receptor binding patterns. Nat. Genet. 2011;43(3):264-268. DOI: 10.1038/ng.759

39. Kakar M., Kanwal C., Davis J.R., Li H., Lim C.S. Geldanamycin, an inhibitor of Hsp90, blocks cytoplasmic retention of progesterone receptors and glucocorticoid receptors via their respective ligand binding domains. AAPS J. 2006;8(4):E718-E728. DOI: 10.1208/ aapsj080481

40. King H.A., Trotter K.W., Archer T.K. Chromatin remodeling during glucocorticoid receptor regulated transactivation. Biochim. Biophys. Acta. 2012;1819;7:716-726. DOI: 10.1016/j.bbagrm.2012.02.019

41. Kino T., Nordeen S.K., Chrousos G.P. Conditional modulation of glucocorticoid receptor activities by CREB-binding protein (CBP) and p300. J. Steroid. Biochem. Mol. Biol. 1999;70(1/3):15-25. DOI: 10.1016/S0960-0760(99)00100-4

42. Klokk T.I., Kurys P., Elbi C., Nagaich A.K., Hendarwanto A., Slagsvold T., Chang C.Y., Hager G.L., Saatcioglu F. Ligand-specific dynamics of the androgen receptor at its response element in living cells. Mol. Cell. Biol. 2007;27(5):1823-1843. DOI: 10.1128/ MCB.01297-06

43. Liu J., DeFranco D.B. Chromatin recycling of glucocorticoid receptors: implications for multiple roles of heat shock protein 90. Mol. Endocrinol. 1999;13(3):355-365. DOI: 10.1210/me.13.3.355

44. Liu J., DeFranco D.B. Protracted nuclear export of glucocorticoid receptor limits its turnover and does not require the exportin 1/CRM1-directed nuclear export pathway. Mol. Endocrinol. 2000;14(1):40-51. DOI: 10.1210/me.14.1.40

45. Mangelsdorf D.J., Thummel C., Beato M., Herrlich P., Schutz G., Umesono K., Blumberg B., Kastner P., Mark M., Chambon P., Evans R.M. The nuclear receptor superfamily: the second decade. Cell. 1995;83(6):835-839. DOI: 10.1016/0092-8674(95)90199-X

46. Marfori M., Mynott A., Ellis J.J., Mehdi A.M., Saunders N.F., Curmi P.M., Forwood J.K., Bodén M., Kobe B. Molecular basis for specificity of nuclear import and prediction of nuclear localization. Biochim. Biophys. Acta. 2011;1813(9):1562-1577. DOI: 10.1016/ j.bbamcr.2010.10.013

47. Merkulov V.M., Merkulova T.I. Structural variants of glucocorticoid receptor binding sites and different versions of positive glucocorticoid responsive elements: Analysis of GR-TRRD database. J. Steroid Biochem. Mol. Biol. 2009;115:1-8. DOI: 10.1016/j.jsbmb.2009.02.003

48. McNally J.G., Müller W.G., Walker D., Wolford R., Hager G.L. The glucocorticoid receptor: rapid exchange with regulatory sites in living cells. Science. 2000;287(5456):1262-1265. DOI:10.1126/science. 287.5456.1262

49. Miranda T.B., Morris S.A., Hager G.L. Complex genomic interactions in the dynamic regulation of transcription by the glucocorticoid receptor. Mol. Cell. Endocrinol. 2013;380(1/2):16-24. DOI: 10.1016/j.mce.2013.03.002

50. Muchardt C., Yaniv M. A human homologue of Sacharomyces cerevizia SNF2/SWI2 and Drosophila bhm genes potentiates transcriptional activation by the glucocorticoid receptor. EMBO J. 1993;12(11):4279-4290.

51. Nagaich A.K., Walker D.A., Wolford R., Hager G.L. Rapid periodic binding and displacement of the glucocorticoid receptor during chromatin remodeling. Mol. Cell. 2004;14:163-174.

52. Nakielny S., Dreyfuss G. Transport of proteins and RNAs in and out of the nucleus. Cell. 1999;99(7):677-690. DOI: 10.1016/S0092-8674(00)81666-9

53. Nemoto T., Ohara-Nemoto Y., Denis M., Gustafsson J.A. The transformed glucocorticoid receptor has a lower steroid-binding affinity than the nontransformed receptor. Biochemistry. 1990;29(7):1880-1886.

54. Nicolaides N.C., Galata Z., Kino T., Chrousos G.P., Charmandari E. The human glucocorticoid receptor: molecular basis of biologic function. Steroids. 2010;75(1):1-12. DOI: 10.1016/j.steroids.2009.09.002

55. Odunuga O.O., Longshaw V.M., Blatch G.L. Hop: more than an Hsp70/Hsp90 adaptor protein. Bioessays. 2004;26(10):1058-1068. DOI: 10.1002/bies.20107

56. Okret S., Wikstrom A.C., Gustafsson J.A. Molybdate-stabilized glucocorticoid receptor: evidence for a receptor heteromer. Biochemistry. 1985;24(23):6581-6586.

57. Olkku A., Mahonen A. Calreticulin mediated glucocorticoid receptor export is involved in beta-catenin translocation and Wnt signaling inhibition in human osteoblastic cells. Bone. 2009;44(4):555-565. DOI: 10.1016/j.bone.2008.11.013

58. Payvar F., Wrange O., Carlstedt-Duke J., Okret S., Gustafsson J.A., Yamamoto K.R. Purified glucocorticoid receptors bind selectively in vitro to a cloned DNA fragment whose transcription is regulated by glucocorticoids in vivo. Proc. Natl. Acad. Sci. USA. 1981;78(11):6628-6632.

59. Perlmann T., Eriksson P., Wrange O. Quantitative analysis of glucocorticoid receptor-DNA interaction at the mouse mammary tumor virus glucocorticoid response element. J. Biol. Chem. 1990;265(8):17222-17229.

60. Perrot-Applanat M., Cibert C., Geraud G., Renoir J.M., Baulieu E.E. The 59 kDa FK506-binding protein, a 90 kDa heat shock protein binding immunophilin (FKBP59-HBI), is associated with the nucleus, the cytoskeleton and mitotic apparatus. J. Cell. Sci. 1995;108 (Pt 5):2037-2051.

61. Picard D., Yamamoto K.R. Two signals mediate hormone-dependent nuclear localization of the glucocorticoid receptor. EMBO J. 1987; 6(11):3333-3340.

62. Pratt W.B. The role of heat shock proteins in regulating the function, folding, and trafficking of the glucocorticoid receptor. J. Biol. Chem. 1993;268(29):21455-21458.

63. Pratt W.B., Toft D.O. Steroid receptor interactions with heat shock protein and immunophilin chaperones. Endocr. Rev. 1997;18(3):306-360. DOI: 10.1210/edrv.18.3.0303

64. Pratt W.B., Galigniana M.D., Morishima Y., Murphy P.J. Role of molecular chaperones in steroid receptor action. Essays Biochem. 2004;40:41-58.

65. Rayasam G.V., Elbi C., Walker D.A., Wolford R.G., Fletcher T.M., Edwards D.P., Hager G.L. Ligand specific dynamics of the progesterone receptor in living cells and during chromatin remodeling in vitro. Mol. Cell. Biol. 2005;25(6):2406-2418. DOI: 10.1128/ MCB.25.6.2406-2418.2005

66. Richard-Foy H., Hager G.L. Sequence-specific positioning of nucleosomes over the steroid-inducible MMTV promoter. EMBO J. 1987; 6(8):2321-2328.

67. Rousseau G.G., Higgins S.J., Baxter J.D., Gelfand D., Tomkins G.M. Binding of glucocorticoid receptors to DNA. J. Biol. Chem. 1975; 250(15):6015-6021.

68. Sackey F.N., Haché R.J., Reich T., Kwast-Welfeld J., Lefebvre Y.A. Determinants of subcellular distribution of the glucocorticoid receptor. Mol. Endocrinol. 1996;10(10):1191-1205. DOI: 10.1210/mend.10.10.9121487

69. Sanchez E.R., Hirst M., Scherrer L.C., Tang H.-Y., Welsh M.J., Harmon J.M., Simons S.S. Jr., Ringold G.M., Pratt W.B. Hormone-free mouse glucocorticoid receptors overexpressed in Chinese hamster ovary cells are localized to the nucleus and are associated with both hsp70 and hsp90. J. Biol. Chem. 1990;265(33):20123-20130.

70. Savory J.G., Hsu B., Laquian I.R., Giffin W., Reich T., Haché R.J., Lefebvre Y.A. Discrimination between NL1- and NL2-mediated nuclear localization of the glucocorticoid receptor. Mol. Cell. Biol. 1999;19(2):1025-1037.

71. Schmid W., Cole T.J., Blendy J.A., Schutz G. Molecular genetic analysis of glucocorticoid signalling in development. J. Steroid. Biochem. Mol. Biol. 1995;53(1/6):33-35. DOI: 10.1016/0960-0760(95)00038-2

72. Schoneveld O.J., Gaemers I.C., Lamers W.H. Mechanisms of glucocorticoid signaling. Biochem. Biophys. Acta. 2004;1680(2):114-128. DOI: 10.1016/j.bbaexp.2004.09.004

73. Sharp Z.D., Mancini M.G., Hinojos C.A., Dai F., Berno V., Szafran A.T., Smith K.P., Lele T.T., Ingber D.E., Mancini M.A. Estrogen-receptor-alpha exchange and chromatin dynamics are ligandand domain-dependent. J. Cell. Sci. 2006;119(19):4101-4116. DOI: 10.1242/ jcs.03161

74. Simons S.S. Jr., Martinez H.M., Garcea R.L., Baxter J.D., Tomkins G.M. Interaction of glucocorticoid receptor-steroid complexes with acceptor sites. J. Biol. Chem. 1976;251(2):334-343.

75. Stavreva D.A., Müller W.G., Hager G.L., Smith C.L., McNally J.G. Rapid glucocorticoid receptor exchange at a promoter is coupled to transcription and regulated by chaperones and proteasomes. Mol. Cell. Biol. 2004;24(7):2682-2697. DOI: 10.1128/MCB.24.7.2682- 2697.2004

76. Stavreva D.A., Varticovski L., Hager G.L. Complex dynamics of transcription regulation. Biochim. Biophys. Acta. 2012;1819(7):657-666. DOI: 10.1016/j.bbagrm.2012.03.004

77. Stavreva D.A., Wiench M., John S., Conway-Campbell B.L., McKenna M.A., Pooley J.R., Johnson T.A., Voss T.C., Lightman S.L., Hager G.L. Ultradian hormone stimulation induces glucocorticoid receptor-mediated pulses of gene transcription. Nat. Cell Biol. 2009; 11(9):1093-1102. DOI: 10.1038/ncb1922

78. Tago K., Tsukahara F., Naruse M., Yoshioka T., Takano K. Regulation of nuclear retention of glucocorticoid receptor by nuclear Hsp90. Mol. Cell. Endocrinol. 2004;213(2):131-138. DOI: 10.1016/j.mce.2003.10.057

79. Truss M., Bartsch J., Schelbert A., Hache R.J., Beato M. Hormone induces binding of receptors and transcription factors to a rearranged nucleosome on the MMTV promoter in vivo. EMBO J.1995;14(8):1737-1751.

80. Vandevyver S., Dejager L., Libert C. On the trail of the glucocorticoid receptor: into the nucleus and back. Traffic. 2012;13(3):364-374.DOI: 10.1111/j.1600-0854.2011.01288.x

81. Wallberg A.E., Flinn E.M., Gustafsson J.A., Wright A.P. Recruitment of chromatin remodelling factors during gene activation via the glucocorticoid receptor N-terminal domain. Biochem. Soc. Trans. 2000;28(4):410-414. DOI: 10.1042/bst0280410

82. Walker D., Htun H., Hager G.L. Using inducible vectors to study intracellular trafficking of GFP-tagged steroid/nuclear receptors in living cells. Methods. 1999;19(3):386-393. DOI: 10.1006/meth.1999.0874

83. Walther R.F., Lamprecht C., Ridsdale A., Groulx I., Lee S., Lefebvre Y.A., Hache R.J. Nuclear export of the glucocorticoid receptor is accelerated by cell fusion-dependent release of calreticulin. J. Biol. Chem. 2003;278(39):37858-37864. DOI: 10.1074/jbc.M306356200

84. Wrange O., Carlstedt-Duke J., Gustaffson J.A. Purification on the glucocorticoid reseptor from rat liver citosol. J. Biol. Chem. 1979;254(18):9284-9290.

85. Yang J., DeFranco D.B. Differential roles of heat shock protein 70 in the in vitro nuclear import of glucocorticoid receptor and simian virus 40 large tumor antigen. Mol. Cell. Biol. 1994;14(8):5088-5098. DOI: 10.1128/MCB.14.8.5088


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