Dissecting functions of the N-terminal domain and GAS-site recognition in STAT3 nuclear trafficking

Cellular Signalling

Volumn 28, Issue 8, 2016, Pages 810-825

  Martincuks, Antons ^a   Fahrenkamp, Dirk ^a   Haan, Serge ^a,b   Herrmann, Andreas ^a,c   Küster, Andrea ^a   Müller Newen, Gerhard ^a  

^a RWTH AACHEN UNIVERSITY   (Germany)

^b UNIVERSITY OF LUXEMBOURG   (Luxembourg)

^c CITY OF HOPE NATIONAL MEDICAL CENTER   (United States)

Author keywords

DNA binding; Gene induction; Importin; N terminal domain; Nuclear translocation; STAT3

Indexed keywords

CYTOKINE; CYTOKINE RECEPTOR; DIMER; DNA; INTERLEUKIN 6; ISOPROTEIN; JANUS KINASE; KARYOPHERIN ALPHA; LEPTOMYCIN B; PROTEIN SH2; RECEPTOR SUBUNIT; STAT1 PROTEIN; STAT3 PROTEIN; TRANSCRIPTION FACTOR; LIGAND; MUTANT PROTEIN; PROTEIN BINDING;

AMINO TERMINAL SEQUENCE; ANIMAL CELL; ARTICLE; BINDING ASSAY; CANCER GROWTH; CELLULAR DISTRIBUTION; CONTROLLED STUDY; CYTOPLASM; DELETION MUTANT; DNA BINDING; DNA SEQUENCE; GENETIC TRANSCRIPTION; HEMATOPOIESIS; HUMAN; IMMUNOFLUORESCENCE; INFLAMMATION; MOUSE; NONHUMAN; NUCLEAR IMPORT; NUCLEAR LOCALIZATION SIGNAL; NUCLEOCYTOPLASMIC TRANSPORT; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; RECOGNITION; WILD TYPE; ACTIVE TRANSPORT; ANIMAL; CELL NUCLEUS; CHEMISTRY; DRUG EFFECTS; GENE DELETION; METABOLISM; NUCLEOTIDE SEQUENCE; PROTEIN MULTIMERIZATION; STRUCTURE ACTIVITY RELATION;

ACTIVE TRANSPORT, CELL NUCLEUS; ALPHA KARYOPHERINS; ANIMALS; BASE SEQUENCE; CELL NUCLEUS; DNA; HUMANS; INTERLEUKIN-6; LIGANDS; MICE; MUTANT PROTEINS; PROTEIN BINDING; PROTEIN DOMAINS; PROTEIN MULTIMERIZATION; SEQUENCE DELETION; STAT3 TRANSCRIPTION FACTOR; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84965017808     PISSN: 08986568     EISSN: 18733913     Source Type: Journal    
DOI: 10.1016/j.cellsig.2016.03.011     Document Type: Article

References (68)

1. Levy D.E., Darnell J.E. Stats: transcriptional control and biological impact. Nat. Rev. Mol. Cell Biol. 2002, 3:651-662.
2. Heinrich P.C., Behrmann I., Haan S., Hermanns H.M., Müller-Newen G., Schaper F. Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem. J. 2003, 374:1-20.
3. Guschin D., Rogers N., Briscoe J., Witthuhn B., Watling D., Horn F., et al. A major role for the protein tyrosine kinase JAK1 in the JAK/STAT signal transduction pathway in response to interleukin-6. EMBO J. 1995, 14:1421-1429.
4. Yu H., Pardoll D., Jove R. STATs in cancer inflammation and immunity: a leading role for STAT3. Nat. Rev. Cancer 2009, 9:798-809.
5. Fagard R., Metelev V., Souissi I., Baran-Marszak F. STAT3 inhibitors for cancer therapy: have all roads been explored?. Jak-Stat 2013, 2.
6. Decker T., Kovarik P., Meinke A. GAS elements: a few nucleotides with a major impact on cytokine-induced gene expression. J. Interf. Cytokine Res. 1997, 17:121-134.
7. Mohr A., Chatain N., Domoszlai T., Rinis N., Sommerauer M., Vogt M., et al. Dynamics and non-canonical aspects of JAK/STAT signalling. Eur. J. Cell Biol. 2012, 91:524-532.
8. Braunstein J., Brutsaert S., Olson R., Schindler C. STATs dimerize in the absence of phosphorylation. J. Biol. Chem. 2003, 278:34133-34140.
9. Meyer T., Vinkemeier U. Nucleocytoplasmic shuttling of STAT transcription factors. Eur. J. Biochem. 2004, 271:4606-4612.
10. Pranada A.L., Metz S., Herrmann A., Heinrich P.C., Müller-Newen G. Real time analysis of STAT3 nucleocytoplasmic shuttling. J. Biol. Chem. 2004, 279:15114-15123.
11. Vogt M., Domoszlai T., Kleshchanok D., Lehmann S., Schmitt A., Poli V., et al. The role of the N-terminal domain in dimerization and nucleocytoplasmic shuttling of latent STAT3. J. Cell Sci. 2011, 124:900-909.
12. Zhang X., Darnell J.E. Functional importance of Stat3 tetramerization in activation of the alpha 2-macroglobulin gene. J. Biol. Chem. 2001, 276:33576-33581.
13. Timofeeva O.A., Tarasova N.I. Alternative ways of modulating JAK-STAT pathway: looking beyond phosphorylation. Jak-Stat 2012, 1:274-284.
14. Zhang L., Badgwell D.B., Bevers J.J., Schlessinger K., Murray P.J., Levy D.E., et al. IL-6 signaling via the STAT3/SOCS3 pathway: functional analysis of the conserved STAT3 N-domain. Mol. Cell. Biochem. 2006, 288:179-189.
15. Ray S., Boldogh I., Brasier A.R. STAT3 NH2-terminal acetylation is activated by the hepatic acute-phase response and required for IL-6 induction of angiotensinogen. Gastroenterology 2005, 129:1616-1632.
16. Ray S., Lee C., Hou T., Bhakat K.K., Brasier A.R. Regulation of signal transducer and activator of transcription 3 enhanceosome formation by apurinic/apyrimidinic endonuclease 1 in hepatic acute phase response. Mol. Endocrinol. 2010, 24:391-401.
17. Ray S., Zhao Y., Jamaluddin M., Edeh C.B., Lee C., Brasier A.R. Inducible STAT3 NH2 terminal mono-ubiquitination promotes BRD4 complex formation to regulate apoptosis. Cell. Signal. 2014, 26:1445-1455.
18. Hou T., Ray S., Lee C., Brasier A.R. The STAT3 NH2-terminal domain stabilizes enhanceosome assembly by interacting with the p300 bromodomain. J. Biol. Chem. 2008, 283:30725-30734.
19. Hu T., Yeh J.E., Pinello L., Jacob J., Chakravarthy S., Yuan G.C., et al. Impact of the N-terminal domain of STAT3 in STAT3-dependent transcriptional activity. Mol. Cell. Biol. 2015, 35:3284-3300.
20. Mohr A., Fahrenkamp D., Rinis N., Müller-Newen G. Dominant-negative activity of the STAT3-Y705F mutant depends on the N-terminal domain. Cell Commun Signal 2013, 11:83.
21. Timofeeva O.A., Tarasova N.I., Zhang X., Chasovskikh S., Cheema A.K., Wang H., et al. STAT3 suppresses transcription of proapoptotic genes in cancer cells with the involvement of its N-terminal domain. Proc. Natl. Acad. Sci. U. S. A. 2013, 110:1267-1272.
22. Stewart M. Molecular mechanism of the nuclear protein import cycle. Nat. Rev. Mol. Cell Biol. 2007, 8:195-208.
23. Pumroy R.A., Cingolani G. Diversification of importin-alpha isoforms in cellular trafficking and disease states. Biochem. J. 2015, 466:13-28.
24. Sekimoto T., Imamoto N., Nakajima K., Hirano T., Yoneda Y. Extracellular signal-dependent nuclear import of Stat1 is mediated by nuclear pore-targeting complex formation with NPI-1, but not Rch1. EMBO J. 1997, 16:7067-7077.
25. Nardozzi J., Wenta N., Yasuhara N., Vinkemeier U., Cingolani G. Molecular basis for the recognition of phosphorylated STAT1 by importin alpha5. J. Mol. Biol. 2010, 402:83-100.
26. Liu L., McBride K.M., Reich N.C. STAT3 nuclear import is independent of tyrosine phosphorylation and mediated by importin-alpha3. Proc. Natl. Acad. Sci. U. S. A. 2005, 102:8150-8155.
27. Ushijima R., Sakaguchi N., Kano A., Maruyama A., Miyamoto Y., Sekimoto T., et al. Extracellular signal-dependent nuclear import of STAT3 is mediated by various importin alphas. Biochem. Biophys. Res. Commun. 2005, 330:880-886.
28. Ma J., Cao X. Regulation of Stat3 nuclear import by importin alpha5 and importin alpha7 via two different functional sequence elements. Cell. Signal. 2006, 18:1117-1126.
29. Herrmann A., Vogt M., Mönnigmann M., Clahsen T., Sommer U., Haan S., et al. Nucleocytoplasmic shuttling of persistently activated STAT3. J. Cell Sci. 2007, 120:3249-3261.
30. Arcone R., Pucci P., Zappacosta F., Fontaine V., Malorni A., Marino G., et al. Single-step purification and structural characterization of human interleukin-6 produced in Escherichia coli from a T7 RNA polymerase expression vector. Eur. J. Biochem. 1991, 198:541-547.
31. Weiergräber O., Hemmann U., Küster A., Müller-Newen G., Schneider J., Rose-John S., et al. Soluble human interleukin-6 receptor: expression in insect cells, purification and characterization. Eur. J. Biochem. 1995, 234:661-669.
32. Costa-Pereira A.P., Tininini S., Strobl B., Alonzi T., Schlaak J.F., Is'harc H., et al. Mutational switch of an IL-6 response to an interferon-gamma-like response. Proc. Natl. Acad. Sci. U. S. A. 2002, 99:8043-8047.
33. Papadopoulos C., Arato K., Lilienthal E., Zerweck J., Schutkowski M., Chatain N., et al. Splice variants of the dual specificity tyrosine phosphorylation-regulated kinase 4 (DYRK4) differ in their subcellular localization and catalytic activity. J. Biol. Chem. 2011, 286:5494-5505.
34. Livak K.J., Schmittgen T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 2001, 25:402-408.
35. Becker S., Groner B., Müller C.W. Three-dimensional structure of the Stat3beta homodimer bound to DNA. Nature 1998, 394:145-151.
36. Gerhartz C., Heesel B., Sasse J., Hemmann U., Landgraf C., Schneider-Mergener J., et al. Differential activation of acute phase response factor/STAT3 and STAT1 via the cytoplasmic domain of the interleukin-6 signal transducer gp130. 1. Definition of a novel phosphotyrosine motif mediating STAT1 activation. J. Biol. Chem. 1996, 271:12991-12998.
37. Shuai K., Liao J., Song M.M. Enhancement of antiproliferative activity of gamma interferon by the specific inhibition of tyrosine dephosphorylation of Stat1. Mol. Cell. Biol. 1996, 16:4932-4941.
38. Strehlow I., Schindler C. Amino-terminal signal transducer and activator of transcription (STAT) domains regulate nuclear translocation and STAT deactivation. J. Biol. Chem. 1998, 273:28049-28056.
39. Meissner T., Krause E., Lodige I., Vinkemeier U. Arginine methylation of STAT1: a reassessment. Cell 2004, 119:587-589. discussion 589-590.
40. Kobe B. Autoinhibition by an internal nuclear localization signal revealed by the crystal structure of mammalian importin alpha. Nat. Struct. Biol. 1999, 6:388-397.
41. Meyer T., Gavenis K., Vinkemeier U. Cell type-specific and tyrosine phosphorylation-independent nuclear presence of STAT1 and STAT3. Exp. Cell Res. 2002, 272:45-55.
42. Bhattacharya S., Schindler C. Regulation of Stat3 nuclear export. J. Clin. Invest. 2003, 111:553-559.
43. Hemmann U., Gerhartz C., Heesel B., Sasse J., Kurapkat G., Grötzinger J., et al. Differential activation of acute phase response factor/Stat3 and Stat1 via the cytoplasmic domain of the interleukin 6 signal transducer gp130. J. Biol. Chem. 1996, 271:12999-13007.
44. Lillemeier B.F., Köster M., Kerr I.M. STAT1 from the cell membrane to the DNA. EMBO J 2001, 20:2508-2517.
45. Herrington J., Rui L., Luo G., Yu-Lee L.Y., Carter-Su C. A functional DNA binding domain is required for growth hormone-induced nuclear accumulation of Stat5B. J. Biol. Chem. 1999, 274:5138-5145.
46. Buettner R., Corzano R., Rashid R., Lin J., Senthil M., Hedvat M., et al. Alkylation of cysteine 468 in Stat3 defines a novel site for therapeutic development. ACS Chem. Biol. 2011, 6:432-443.
47. Teng P., Zhang X., Wu H., Qiao Q., Sebti S.M., Cai J. Identification of novel inhibitors that disrupt STAT3-DNA interaction from a gamma-AApeptide OBOC combinatorial library. Chem. Commun. 2014, 50:8739-8742.
48. Auernhammer C.J., Bousquet C., Melmed S. Autoregulation of pituitary corticotroph SOCS-3 expression: characterization of the murine SOCS-3 promoter. Proc. Natl. Acad. Sci. U. S. A. 1999, 96:6964-6969.
49. Ramana C.V., Kumar A., Enelow R. Stat1-independent induction of SOCS-3 by interferon-gamma is mediated by sustained activation of Stat3 in mouse embryonic fibroblasts. Biochem. Biophys. Res. Commun. 2005, 327:727-733.
50. Schiavone D., Avalle L., Dewilde S., Poli V. The immediate early genes fos and Egr1 become STAT1 transcriptional targets in the absence of STAT3. FEBS Lett. 2011, 585:2455-2460.
51. Meyer T., Marg A., Lemke P., Wiesner B., Vinkemeier U. DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1. Genes Dev. 2003, 17:1992-2005.
52. Xu L., Ji J.J., Le W., Xu Y.S., Dou D., Pan J., et al. The STAT3 HIES mutation is a gain-of-function mutation that activates genes via AGG-element carrying promoters. Nucleic Acids Res. 2015.
53. Wang W.B., Levy D.E., Lee C.K. STAT3 negatively regulates type I IFN-mediated antiviral response. J. Immunol. 2011, 187:2578-2585.
54. Maritano D., Sugrue M.L., Tininini S., Dewilde S., Strobl B., Fu X., et al. The STAT3 isoforms alpha and beta have unique and specific functions. Nat. Immunol. 2004, 5:401-409.
55. Domoszlai T., Martincuks A., Fahrenkamp D., Schmitz-Van de Leur H., Küster A., Müller-Newen G. Consequences of the disease-related L78R mutation for dimerization and activity of STAT3. J. Cell Sci. 2014.
56. Mertens C., Zhong M., Krishnaraj R., Zou W., Chen X., Darnell J.E. Dephosphorylation of phosphotyrosine on STAT1 dimers requires extensive spatial reorientation of the monomers facilitated by the N-terminal domain. Genes Dev. 2006, 20:3372-3381.
57. Sgrignani J., Olsson S., Ekonomiuk D., Genini D., Krause R., Catapano C.V., et al. Molecular determinants for unphosphorylated STAT3 dimerization determined by Integrative Modeling. Biochemistry 2015, 54:5489-5501.
58. Meyer T., Hendry L., Begitt A., John S., Vinkemeier U. A single residue modulates tyrosine dephosphorylation, oligomerization, and nuclear accumulation of stat transcription factors. J. Biol. Chem. 2004, 279:18998-19007.
59. ten Hoeve J., de Jesus Ibarra-Sanchez M., Fu Y., Zhu W., Tremblay M., David M., et al. Identification of a nuclear Stat1 protein tyrosine phosphatase. Mol. Cell. Biol. 2002, 22:5662-5668.
60. Yamamoto T., Sekine Y., Kashima K., Kubota A., Sato N., Aoki N., et al. The nuclear isoform of protein-tyrosine phosphatase TC-PTP regulates interleukin-6-mediated signaling pathway through STAT3 dephosphorylation. Biochem. Biophys. Res. Commun. 2002, 297:811-817.
61. Wang Y., Ning H., Ren F., Zhang Y., Rong Y., Wang Y., et al. GdX/UBL4A specifically stabilizes the TC45/STAT3 association and promotes dephosphorylation of STAT3 to repress tumorigenesis. Mol. Cell 2014, 53:752-765.
62. Ben-Yaakov K., Dagan S.Y., Segal-Ruder Y., Shalem O., Vuppalanchi D., Willis D.E., et al. Axonal transcription factors signal retrogradely in lesioned peripheral nerve. EMBO J. 2012, 31:1350-1363.
63. Cimica V., Chen H.C., Iyer J.K., Reich N.C. Dynamics of the STAT3 transcription factor: nuclear import dependent on Ran and importin-beta1. PLoS One 2011, 6.
64. Kawashima T., Bao Y.C., Minoshima Y., Nomura Y., Hatori T., Hori T., et al. A Rac GTPase-activating protein, MgcRacGAP, is a nuclear localizing signal-containing nuclear chaperone in the activation of STAT transcription factors. Mol. Cell. Biol. 2009, 29:1796-1813.
65. Nishimoto A., Yu Y., Lu Z., Mao X., Ren Z., Watowich S.S., et al. A Ras homologue member I directly inhibits signal transducers and activators of transcription 3 translocation and activity in human breast and ovarian cancer cells. Cancer Res. 2005, 65:6701-6710.
66. Meyer T., Begitt A., Lodige I., van Rossum M., Vinkemeier U. Constitutive and IFN-gamma-induced nuclear import of STAT1 proceed through independent pathways. EMBO J. 2002, 21:344-354.
67. Marg A., Shan Y., Meyer T., Meissner T., Brandenburg M., Vinkemeier U. Nucleocytoplasmic shuttling by nucleoporins Nup153 and Nup214 and CRM1-dependent nuclear export control the subcellular distribution of latent Stat1. J. Cell Biol. 2004, 165:823-833.
68. Kretzschmar A.K., Dinger M.C., Henze C., Brocke-Heidrich K., Horn F. Analysis of Stat3 dimerization by fluorescence resonance energy transfer in living cells. Biochem. J. 2004, 377:289-297.