Folding of the glucocorticoid receptor N-terminal transactivation function: Dynamics and regulation

Molecular and Cellular Endocrinology

Volumn 348, Issue 2, 2012, Pages 450-456

  Kumar, R ^a   Thompson, E B ^b,c  

^a Geisinger Health Geisinger Commonwealth School of Medicine   (United States)

^b University of Texas Medical Branch School of Medicine   (United States)

^c University of Houston   (United States)

Author keywords

Coregulatory proteins; Glucocorticoid receptor; Intrinsically disordered; Protein folding; Transactivation function

Indexed keywords

GLUCOCORTICOID RECEPTOR; REGULATOR PROTEIN;

ALLOSTERISM; AMINO TERMINAL SEQUENCE; HUMAN; IN VIVO STUDY; MOLECULAR RECOGNITION; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN DOMAIN; PROTEIN FOLDING; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; REVIEW; TRANSACTIVATION; TRANSCRIPTION INITIATION; TRANSCRIPTION REGULATION;

ALLOSTERIC REGULATION; ANIMALS; HUMANS; MODELS, MOLECULAR; PHOSPHORYLATION; PROMOTER REGIONS, GENETIC; PROTEIN BINDING; PROTEIN FOLDING; PROTEIN STABILITY; PROTEIN STRUCTURE, SECONDARY; PROTEIN STRUCTURE, TERTIARY; RECEPTORS, GLUCOCORTICOID; SURFACE PROPERTIES; TRANSCRIPTIONAL ACTIVATION;

EID: 82655172634     PISSN: 03037207     EISSN: 18728057     Source Type: Journal    
DOI: 10.1016/j.mce.2011.03.024     Document Type: Review

References (92)

1. Almlof T., Wright A.P.H., Gustafsson J.å. Role of acidic and phosphorylated residues in gene activation by the glucocorticoid receptor. J. Biol. Chem. 1995, 270:17535-17540.
2. Almlof T., Gustafsson J.A., Wright A.P. Role of hydrophobic amino acid clusters in the transactivation activity of the human glucocorticoid receptor. Mol. Cell. Biol. 1997, 17:934-945.
3. Almlof T., Wallberg A.E., Gustafsson J.A., Wright A.P. Role of important hydrophobic amino acids in the interaction between the glucocorticoid receptor τ1-core activation domain and target factors. Biochemistry 1998, 37:9586-9594.
4. Bain D.L., Franden M.A., McManaman J.L., Takimoto G.S., Horwitz K.B. The N-terminal region of the human progesterone A-receptor. Structural analysis and the influence of the DNA binding domain. J. Biol. Chem. 2000, 275:7313-7320.
5. Baskakov I.V., Bolen D.W. TMAO counteracts urea effects on rabbit muscle LDH function: a test of the counteraction hypothesis. Biophys. J. 1998, 74:2666-2673.
6. Baskakov I.V., Bolen D.W. Forcing thermodynamically unfolded proteins to fold. J. Biol. Chem. 1998, 273:4831-4834.
7. Baskakov I.V., Kumar R., Srinivasan G., Ji Y., Bolen D.W., Thompson E.B. Trimethylamine N-oxide-induced cooperative folding of an intrinsically unfolded transcription-activating fragment of human glucocorticoid receptor. J. Biol. Chem. 1999, 274:10693-10696.
8. Beck I.M., Vanden Berghe W., Vermeulen L., Yamamoto K.R., Haegeman G., De Bosscher K. Crosstalk in inflammation: the interplay of glucocorticoid receptor-based mechanisms and kinases and phosphatases. Endocr. Rev. 2009, 30:830-882.
9. Benecke A., Chambon P., Gronemeyer H. Synergy between estrogen receptor alpha activation functions AF1 and AF2 mediated by transcription intermediary factor TIF2. EMBO Rep. 2000, 1:151-157.
10. Bevan C.L., Hoare S., Claessens F., Heery D.M., Parker M.G. The AF1 and AF2 domains of the androgen receptor interact with distinct regions of SRC1. Mol. Cell. Biol. 1999, 19:8383-8392.
11. Bia C., Biwersi J., Verkman A.S., Matthay M.A. A mouse model to test the in vivo efficacy of chemical chaperones. J. Pharmacol. Toxicol. Methods 1998, 40:39-45.
12. Bledsoe R.K., Montana V.G., Stanley T.B., Delves C.J., Apolito C.J., McKee D.D., Consler T.G., Parks D.J., Stewart E.L., Willson T.M., Lambert M.H., Moore J.T., Pearce K.H., Xu H.E. Crystal structure of the glucocorticoid receptor ligand binding domain reveals a novel mode of receptor dimerization and coactivator recognition. Cell 2002, 110:93-105.
13. Blind R.D., Garabedian M.J. Differential recruitment of glucocorticoid receptor phospho-isoforms to glucocorticoid-induced genes. J. Steroid Biochem. Mol. Biol. 2008, 109:150-157.
14. Bocquel M.T., Kumar V., Stricker C., Chambon P., Gronemeyer H. The contribution of the N- and C-terminal regions of steroid receptors to activation of transcription is both receptor and cell-specific. Nucleic Acids Res. 1989, 17:2581-2595.
15. Bodwell J.E., Hu L.M., Hu J.M., Ortí E., Munck A. Glucocorticoid receptors: ATP-dependent cycling and hormone-dependent hyper-phosphorylation. J. Steroid Biochem. Mol. Biol. 1993, 47:31-38.
16. Bodwell J.E., Webster J.C., Jewell C.M., Cidlowski J.A., Hu J., Munck A. Glucocorticoid receptor phosphorylation: overview, function and cell cycle dependence. J. Steroid Biochem. Mol. Biol. 1998, 65:91-99.
17. Bolen D.W., Rose G.D. Structure and energetics of the hydrogen-bonded backbone in protein folding. Annu. Rev. Biochem. 2008, 77:339-362.
18. Brzozowski A.M., Pike A.C., Dauter Z., Hubbard R.E., Bonn T., Engstrom O., Ohman L., Greene G.L., Gustafsson J.A., Carlquist M. Molecular basis of agonism and antagonism in the oestrogen receptor. Nature 1997, 389:753-758.
19. Burg M.D. Molecular basis of osmotic regulation. Am. J. Physiol. 1995, 268:F983-F996.
20. Chandra V., Huang P., Hamuro Y., Raghuram S., Wang Y., Burris T.P., Rastinejad F. Structure of the intact PPAR-gamma-RXR- nuclear receptor complex on DNA. Nature 2008, 456:350-356.
21. Chen W., Dang T., Blind R.D., Wang Z., Cavasotto C.N., Hittelman A.B., Rogatsky I., Logan S.K., Garabedian M.J. Glucocorticoid receptor phosphorylation differentially affects target gene expression. Mol. Endocrinol. 2008, 22:1754-1766.
22. Combet C., Blanchet C., Geourjon C., Deléage G. NPS@: network protein sequence analysis. Trends Biochem. Sci. 2000, 25:147-150.
23. Copik A.J., Miller A.L., Yong X., Webb M.S., Kumar R., Thompson E.B. Activation function 1 of glucocorticoid receptor binds TATA-binding protein in vitro and in vivo. Mol. Endocrinol. 2006, 20:1218-1230.
24. Crivici A., Ikura M. Molecular and structural basis of target recognition by calmodulin. Annu. Rev. Biophys. Biomol. Struct. 1995, 24:85-116.
25. Dahlman-Wright K., Almlöf T., McEwan I.J., Gustafsson J.A., Wright A.P. Delineation of a small region within the major transactivation domain of the human glucocorticoid receptor that mediates transactivation of gene expression. Proc. Natl. Acad. Sci. U.S.A. 1994, 91:1619-1623.
26. Dahlman-Wright K., Baumann H., McEwan I.J., Almlöf T., Wright A.P., Gustafsson J.A., Härd T. Structural characterization of a minimal functional transactivation domain from the human glucocorticoid receptor. Proc. Natl. Acad. Sci. U.S.A. 1995, 92:1699-1703.
27. Dalman F.C., Sanchez E.R., Lin A.L., Perini F., Pratt W.B. Localization of phosphorylation sites with respect to the functional domains of the mouse L cell glucocorticoid receptor. J. Biol. Chem. 1998, 263:12259-12267.
28. Davies P., Watt K., Kelly S.M., Clark C., Price N.C., McEwan I.J. Consequences of poly-glutamine repeat length for the conformation and folding of the androgen receptor amino-terminal domain. J. Mol. Endocrinol. 2008, 41:301-314.
29. De Bosscher K., Vanden Berghe W., Beck I.M., Van Molle W., Hennuyer N., Hapgood J., Libert C., Staels B., Louw A., Haegeman G. A fully dissociated compound of plant origin for inflammatory gene repression. Proc. Natl. Acad. Sci. U.S.A. 2005, 102:15827-15832.
30. De Bosscher K. Selective glucocorticoid receptor modulators. J. Steroid Biochem. Mol. Biol. 2010, 120:96-104.
31. Dosztányi Z., Csizmók V., Tompa P., Simon I. IUPred: the prediction of intrinsically unstructured regions of proteins based on estimated energy content. Bioinformatics 2005, 21:3433-3434.
32. Dunker A.K., Uversky V.N. Signal transduction via unstructured protein conduits. Nat. Chem. Biol. 2008, 4:229-230.
33. Dyson H.J., Wright P.E. Coupling of folding and binding for unstructured proteins. Curr. Opin. Struct. Biol. 2002, 12:54-60.
34. Ford J., McEwan I.J., Wright A.P., Gustafsson J.A. Involvement of the transcription factor IID protein complex in gene activation by the N-terminal transactivation domain of the glucocorticoid receptor in vitro. Mol. Endocrinol. 1997, 11:1467-1475.
35. Frankel A.D., Kim P.S. Modular structure of transcription factors: Implications for gene regulation. Cell 1991, 65:717-719.
36. Garza A.S., Khan S.H., Kumar R. Site-specific phosphorylation induces functionally active conformation in the intrinsically disordered N-terminal activation function (AF1) domain of the glucocorticoid receptor. Mol. Cell. Biol. 2010, 30:220-230.
37. Giguere V., Hollenberg S.M., Rosenfeld M.G., Evans R.M. Functional domains of the human glucocorticoid receptor. Cell 1986, 46:645-652.
38. Glass C.K., Rose D.W., Rosenfeld M.G. Nuclear receptor coactivators. Curr. Opin. Cell Biol. 1997, 9:222-232.
39. Gu J., Hilser V.J. Predicting the energetics of conformational fluctuations in proteins from sequence: a strategy for profiling the proteome. Structure 2008, 16:1627-1637.
40. Hittelman A.B., Burakov D., Iniguez-Lluhi J.A., Freedman L.P., Garabedian M.J. Differential regulation of glucocorticoid receptor transcriptional activation via AF-1-associated proteins. EMBO J. 1999, 18:5380-5388.
41. Hollenberg S.M., Weinberger C., Ong E.S., Cerelli G., Oro A., Lebo R., Thompson E.B., Rosenfeld M.G., Evans R.M. Primary structure and expression of a functional human glucocorticoid receptor cDNA. Nature 1985, 318:635-641.
42. Hollenberg S.M., Giguère V., Segui P., Evans R.M. Colocalization of DNA-binding and transcriptional activation functions in the human glucocorticoid receptor. Cell 1987, 49:39-46.
43. Horwitz K.B., Jackson T.A., Bain D.L., Richer J.K., Takimoto G.S., Tung L. Nuclear receptor coactivators and corepressors. Mol. Endocrinol. 1996, 10:1167-1177.
44. Iakoucheva L.M., Brown C.J., Lawson J.D., Obradovic Z., Dunker A.K. Intrinsic disorder in cell-signaling and cancer-associated proteins. J. Mol. Biol. 2002, 323:573-584.
45. Iakoucheva L.M., Radivojac P., Brown C.J., O'Connor T.R., Sikes J.G., Obradovic Z., Dunker A.K. The importance of intrinsic disorder for protein phosphorylation. Nucleic Acids Res. 2004, 32:1037-1049.
46. Iniguez-Lluhi J.A., Lou D.Y., Yamamoto K.R. Three amino acid substitutions selectively disrupt the activation but not the repression function of the glucocorticoid receptor N terminus. J. Biol. Chem. 1997, 272:4149-4156.
47. Keightley M.C., Fuller P.J. Cortisol resistance and the guinea pig glucocorticoid receptor. Steroids 1995, 60:87-92.
48. Waf1/Cip1/Sdi1 in the free and Cdk2-bound state: conformational disorder mediates binding diversity. Proc. Natl. Acad. Sci. U.S.A. 1996, 93:11504-11509.
49. Kumar R., Thompson E.B. Structure and functions of the nuclear hormone receptors. Steroids 1999, 64:310-319.
50. Kumar R., Baskakov I.V., Srinivasan G., Bolen D.W., Lee J.C., Thompson E.B. Inter-domain signaling in a two-domain fragment of the human glucocorticoid receptor. J. Biol. Chem. 1999, 274:24737-24741.
51. Kumar R., Lee J.C., Bolen D.W., Thompson E.B. The osmolyte-induced conformation of the glucocorticoid receptor AF1/tau1 domain binds coregulators. J. Biol. Chem. 2001, 276:18146-18152.
52. Kumar R., Thompson E.B. Transactivation functions of the N-terminal domains of nuclear hormone receptors: protein folding and coactivator interactions. Mol. Endocrinol. 2003, 17:1-10.
53. Kumar R., Betney R., Li J., Thompson E.B., McEwan I.J. Induced α-helix structure in the AF1 of the androgen receptor upon binding transcription factor TFIIF. Biochemistry 2004, 43:3008-3013.
54. Kumar R., Volk D.E., Li J., Gorenstein D.G., Lee J.C., Thompson E.B. TBP binding induces structure in the recombinant glucocorticoid receptor AF1 domain. Proc. Natl. Acad. Sci. U.S.A. 2004, 101:16425-16430.
55. Kumar R., Serrette J.M., Khan S.H., Miller A.L., Thompson E.B. Differential effects of osmolytes on the induced folding of the glucocorticoid receptor AF1 domain. Arch. Biochem. Biophys. 2007, 465:452-460.
56. Kumar R. Osmolyte-induced folding of an intrinsically disordered region of glucocorticoid receptor. J. Recept. Signal Trans. 2008, 28:465-474.
57. Kumar R., Litwack G. Structural and functional relationships of the steroid hormone receptors' N-terminal transactivation domain. Steroids 2009, 74:877-883.
58. Kumar R., Thompson E.B. Intramolecular signaling between the glucocorticoid receptor AF1 and DNA binding domains: Influence of AF1 flanking sequences within the N-terminal domain on the structure and functions of AF1. Arch. Biochem. Biophys. 2010, 496:140-145.
59. Lees J.A., Fawell S.E., Parker M.G. Identification of two transactivation domains in the mouse oestrogen receptor. Nucleic Acids Res. 1989, 17:5477-5487.
60. Lefstin J.A., Yamamoto K.R. Allosteric effects of DNA on transcriptional regulators. Nature 1998, 392:885-888.
61. Liu J., Perumal N.B., Oldfield C.J., Su E.W., Uversky V.N., Dunker A.K. Intrinsic disorder in transcription factors. Biochemistry 2006, 45:6873-6888.
62. Loven M.A., Muster N., Yates J.R., Nardulli A.M. A novel estrogen receptor alpha-associated protein, template-activating factor I beta, inhibits acetylation and transactivation. Mol. Endocrinol. 2003, 17:67-78.
63. Lu N.Z., Cidlowski J.A. Translational regulatory mechanisms generate N-terminal glucocorticoid receptor isoforms with unique transcriptional target genes. Mol. Cell 2005, 18:331-342.
64. Luisi B.F., Xu W.X., Otwinowski Z., Freedman L.P., Yamamoto K.R., Sigler P.B. Crystallographic analysis of the interaction of the glucocorticoid receptor with DNA. Nature 1991, 352:497-505.
65. McEwan I.J., Dahlman-Wright K., Ford J., Wright A.P. Functional interaction of the c-Myc transactivation domain with TATA binding protein: evidence for an induced fit model of transactivation domain folding. Biochemistry 1996, 35:9584-9593.
66. McKenna N.J., Lanz R.B., O'Malley B.W. Nuclear receptor coregulators: cellular and molecular biology. Endocr. Rev. 1999, 20:321-344.
67. McNally J.G., Muller W.G., Walker D., Wolford R., Hager G.L. The glucocorticoid receptor: rapid exchange with regulatory sites in living cells. Science 2000, 287:1262-1265.
68. Meijsing S.H., Pufall M.A., So A.Y., Bates D.L., Chen L., Yamamoto K.R. DNA binding site sequence directs glucocorticoid receptor structure and activity. Science 2009, 324:407-410.
69. Miesfeld R., Godowski P.J., Maler B.A., Yamamoto K.R. Glucocorticoid receptor mutants that define a small region sufficient for enhancer activation. Science 1987, 236:423-427.
70. Miller A.L., Webb M.S., Copik A.J., Wang Y., Johnson B.H., Kumar R., Thompson E.B. p38 Mitogen-activated protein kinase (MAPK) is a key mediator in glucocorticoid-induced apoptosis of lymphoid cells: correlation between p38 MAPK activation and site-specific phosphorylation of the human glucocorticoid receptor at serine 211. Mol. Endocrinol. 2005, 19:1569-1583.
71. Miller A.L., Garza A.S., Johnson B.H., Thompson E.B. Pathway interactions between MAPKs, mTOR, PKA, and the glucocorticoid receptor in lymphoid cells. Cancer Cell Int. 2007, 28:7-13.
72. Miller A.L., Webb M.S., Thompson E.B. Comparison of two structurally diverse glucocorticoid receptor agonists: cortivazol selectively regulates a distinct set of genes separate from dexamethasone in CEM cells. Steroids 2007, 72:673-681.
73. Namba K. Roles of partly unfolded conformations in macromolecular self-assembly. Genes Cells 2001, 6:1-12.
74. Onate S.A., Boonyaratanakornkit V., Spencer T.E., Tsai S.Y., Tsai M.J., Edwards D.P., O'Malley B.W. The steroid receptor coactivator-1 contains multiple receptor interacting and activation domains that cooperatively enhance the activation function 1 (AF1) and AF2 domains of steroid receptors. J. Biol. Chem. 1998, 273:12101-12108.
75. Powell S.M., Christiaens V., Voulgaraki D., Waxman J., Claessens F., Bevan C.L. Mechanisms of androgen receptor signaling via steroid receptor coactivator-1 in prostate. Endocr. Relat. Cancer 2004, 11:117-130.
76. Prilusky J., Felder C.E., Zeev-Ben-Mordehai T., Rydberg E.H., Man O., Beckman J.S., Silman I., Sussman J.L. FoldIndex: a simple tool to predict whether a given protein sequence is intrinsically unfolded. Bioinformatics 2005, 21:3435-3438.
77. Reid J., Kelly S.M., Watt K., Price N.C., McEwan I.J. Conformational analysis of the androgen receptor amino-terminal domain involved in transactivation. Influence of structure-stabilizing solutes and protein-protein interactions. J. Biol. Chem. 2002, 277:20079-20086.
78. Romero P., Obradovic Z., Dunker A.K. Natively disordered proteins: functions and predictions. Appl. Bioinformatics 2004, 3:105-113.
79. Sartorius C.A., Melville M.Y., Hovland A.R., Tung L., Takimoto G.S., Horwitz K.B. A third transactivation function (AF3) of human progesterone receptors located in the unique N-terminal segment of the B-isoform. Mol. Endocrinol. 1994, 8:1347-1360.
80. Schoch G.A., D'Arcy B., Stihle M., Burger D., Bär D., Benz J., Thoma R., Ruf A. Molecular switch in the glucocorticoid receptor: active and passive antagonist conformations. J. Mol. Biol. 2010, 395:568-577.
81. Shen F., Triezenberg S.J., Hensley P., Porter D., Knutson J.R. Transcriptional activation domain of the herpesvirus protein VP16 becomes conformationally constrained upon interaction with basal transcription factors. J. Biol. Chem. 1996, 271:4827-4837.
82. Sigler P.B. Acid blobs and negative noodles. Nature 1988, 333:210-212.
83. Stenoien D.L., Patel K., Mancini M.G., Dutertre M., Smith C.L., O'Malley B.W., Mancini M.A. FRAP reveals that mobility of oestrogen receptor-alpha is ligand- and proteasome-dependent. Nat. Cell Biol. 2001, 3:15-23.
84. Tompa P. Intrinsically unstructured proteins evolve by repeat expansion. Bioessays 2003, 25:847-855.
85. Tompa P., Fuxreiter M. Fuzzy complexes: polymorphism and structural disorder in protein-protein interactions. Trends Biochem. Sci. 2008, 33:2-8.
86. Tora L., Gronemeyer H., Turcotte B., Gaub M.P., Chambon P. The N-terminal region of the chicken progesterone receptor specifies target gene activation. Nature 1988, 333:185-188.
87. Uversky V.N., Gillespie J.R., Fink A.L. Why are " natively unfolded" proteins unstructured under physiologic conditions?. Proteins 2000, 41:415-427.
88. Ward J.J., Sodhi J.S., McGuffin L.J., Buxton B.F., Jones D.T. Prediction and functional analysis of native disorder in proteins from the three kingdoms of life. J. Mol. Biol. 2004, 337:635-645.
89. Wang S., Gu J., Larson S.A., Whitten S.T., Hilser V.J. Denatured-state energy landscapes of a protein structural database reveal the energetic determinants of a framework model for folding. J. Mol. Biol. 2008, 381:1184-1201.
90. Warnmark A., Wikstrom A., Wright A.P., Gustafsson J.A., Hard T. The N-terminal regions of estrogen receptor α and β are unstructured in vitro and show different TBP binding properties. J. Biol. Chem. 2001, 276:45939-45944.
91. Yamamoto K.R., Darimont B.D., Wagner R.L., Iniguez-Lluhi J.A. Building transcriptional regulatory complexes: signals and surfaces. Cold Spring Harb. Symp. Quant. Biol. 1998, 63:587-598.
92. Yancey P.H., Clark M.E., Hand S.C., Bowlus R.D., Somero G.N. Living with water stress: evolution of osmolyte systems. Science 1982, 217:1214-1222.