Signal integration and gene induction by a functionally distinct STAT3 phosphoform

Molecular and Cellular Biology

Volumn 34, Issue 10, 2014, Pages 1800-1811

  Waitkus, Matthew S ^a,b   Chandrasekharan, Unni M ^a   Willard, Belinda ^a   Tee, Thomas L ^a   Hsieh, Jason K ^a   Przybycin, Christopher G ^a   Rini, Brian I ^c   DiCorleto, Paul E ^a,b  

^a LERNER RESEARCH INSTITUTE   (United States)

^b CLEVELAND STATE UNIVERSITY   (United States)

^c TAUSSIG CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EPIDERMAL GROWTH FACTOR RECEPTOR; GLYCOGEN SYNTHASE KINASE 3ALPHA; GLYCOGEN SYNTHASE KINASE 3BETA; INTERLEUKIN 6; PROTEINASE ACTIVATED RECEPTOR 1; SERINE; STAT3 PROTEIN; THREONINE;

ARTICLE; CONTROLLED STUDY; ENDOTHELIUM CELL; GENE EXPRESSION; GENE INDUCTION; HUMAN; HUMAN CELL; KIDNEY CARCINOMA; KIDNEY TUMOR; LIQUID CHROMATOGRAPHY; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; TANDEM MASS SPECTROMETRY;

CARCINOMA, RENAL CELL; CELLS, CULTURED; EARLY GROWTH RESPONSE PROTEIN 1; EPIDERMAL GROWTH FACTOR; GLYCOGEN SYNTHASE KINASE 3; HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS; HUMANS; KIDNEY NEOPLASMS; PHOSPHORYLATION; PROMOTER REGIONS, GENETIC; PROTEIN BINDING; PROTEIN PROCESSING, POST-TRANSLATIONAL; RECEPTOR, EPIDERMAL GROWTH FACTOR; RECEPTOR, PAR-1; SIGNAL TRANSDUCTION; STAT3 TRANSCRIPTION FACTOR; TRANSCRIPTIONAL ACTIVATION;

EID: 84899151739     PISSN: 02707306     EISSN: 10985549     Source Type: Journal    
DOI: 10.1128/MCB.00034-14     Document Type: Article

References (54)

1. Stark GR, Darnell JE. 2012. The JAK-STAT pathway at twenty. Immunity 36:503-514. http://dx.doi.org/10.1016/j.immuni.2012.03.013.
2. Yu H, Pardoll D, Jove R. 2009. STATs in cancer inflammation and immunity: a leading role for STAT3. Nat. Rev. Cancer. 9:798-809. http://dx.doi.org/10.1038/nrc2734.
3. Levy DE, Inghirami G. 2006. STAT3: a multifaceted oncogene. Proc. Natl. Acad. Sci. U. S. A. 103:10151-10152. http://dx.doi.org/10.1073/pnas.0604042103.
4. Aznar S, Valerón PF, del Rincon SV, Pérez LF, Perona R, Lacal JC. 2001. Simultaneous tyrosine and serine phosphorylation of STAT3 transcription factor is involved in Rho A GTPase oncogenic transformation. Mol. Biol. Cell 12:3282-3294. http://dx.doi.org/10.1091/mbc.12.10.3282.
5. Kim LC, Song L, Haura EB. 2009. Src kinases as therapeutic targets for cancer. Nat. Rev. Clin. Oncol. 6:587-595. http://dx.doi.org/10.1038/nrclinonc.2009.129.
6. Sen M, Joyce S, Panahandeh M, Li C, Thomas SM, Maxwell J, Wang L, Gooding WE, Johnson DE, Grandis JR. 2012. Targeting Stat3 abrogates EGFR inhibitor resistance in cancer. Clin. Cancer Res. 18:4986-4996. http://dx.doi.org/10.1158/1078-0432.CCR-12-0792.
7. Sen M, Thomas SM, Kim S, Yeh JI, Ferris RL, Johnson JT, Duvvuri U, Lee J, Sahu N, Joyce S, Freilino ML, Shi H, Li C, Ly D, Rapireddy S, Etter JP, Li P-K, Wang L, Chiosea S, Seethala RR, Gooding WE, Chen X, Kaminski N, Pandit K, Johnson DE, Grandis JR. 2012. First-inhuman trial of a STAT3 decoy oligonucleotide in head and neck tumors: implications for cancer therapy. Cancer Discov. 2:694-705. http://dx.doi.org/10.1158/2159-8290.CD-12-0191.
8. Aggarwal BB, Kunnumakkara AB, Harikumar KB, Gupta SR, Tharakan ST, Koca C, Dey S, Sung B. 2009. Signal transducer and activator of transcription-3, inflammation, and cancer: how intimate is the relationship? Ann. N. Y. Acad. Sci. 1171:59-76. http://dx.doi.org/10.1111/j.1749-6632.2009.04911.x.
9. Iwasaki H, Kovacic JC, Olive M, Beers JK, Yoshimoto T, Crook MF, Tonelli LH, Nabel EG. 2010. Disruption of protein arginine Nmethyltransferase 2 regulates leptin signaling and produces leanness in vivo through loss of STAT3 methylation. Circ. Res. 107:992-1001. http://dx.doi.org/10.1161/CIRCRESAHA.110.225326.
10. Yuan Z-L, Guan Y-J, Chatterjee D, Chin YE. 2005. Stat3 dimerization regulated by reversible acetylation of a single lysine residue. Science 307:269-273. http://dx.doi.org/10.1126/science.1105166.
11. Sestito R, Madonna S, Scarponi C, Cianfarani F, Failla CM, Cavani A, Girolomoni G, Albanesi C. 2011. STAT3-dependent effects of IL-22 in human keratinocytes are counterregulated by sirtuin 1 through a direct inhibition of STAT3 acetylation. FASEB J. 25:916-927. http://dx.doi.org/10.1096/fj.10-172288.
12. Nie Y, Erion DM, Yuan Z, Dietrich M, Shulman GI, Horvath TL, Gao Q. 2009. STAT3 inhibition of gluconeogenesis is downregulated by SirT1. Nat. Cell Biol. 11:492-500. http://dx.doi.org/10.1038/ncb1857.
13. Zhong Z, Wen Z, Darnell JE. 1994. Stat3: a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6. Science 264:95-98. http://dx.doi.org/10.1126/science.8140422.
14. Wen Z, Darnell JE. 1997. Mapping of Stat3 serine phosphorylation to a single residue (727) and evidence that serine phosphorylation has no influence on DNA binding of Stat1 and Stat3. Nucleic Acids Res. 25:2062-2067. http://dx.doi.org/10.1093/nar/25.11.2062.
15. Wen Z, Zhong Z, Darnell JE. 1995. Maximal activation of transcription by Stat1 and Stat3 requires both tyrosine and serine phosphorylation. Cell 82:241-250. http://dx.doi.org/10.1016/0092-8674(95)90311-9.
16. Yang J, Huang J, Dasgupta M, Sears N, Miyagi M, Wang B, Chance MR, Chen X, Du Y, Wang Y, An L, Wang Q, Lu T, Zhang X, Wang Z, Stark GR. 2010. Reversible methylation of promoter-bound STAT3 by histonemodifying enzymes. Proc. Natl. Acad. Sci. U. S. A. 107:21499-21504. http://dx.doi.org/10.1073/pnas.1016147107.
17. Song L, Turkson J, Karras JG, Jove R, Haura EB. 2003. Activation of Stat3 by receptor tyrosine kinases and cytokines regulates survival in human non-small cell carcinoma cells. Oncogene 22:4150-4165. http://dx.doi.org/10.1038/sj.onc.1206479.
18. Guschin D, Rogers N, Briscoe J, Witthuhn B, Watling D, Horn F, Pellegrini S, Yasukawa K, Heinrich P, Stark GR. 1995. A major role for the protein tyrosine kinase JAK1 in the JAK/STAT signal transduction pathway in response to interleukin-6. EMBO J. 14:1421-1429.
19. Schuringa JJ, Schepers H, Vellenga E, Kruijer W. 2001. Ser727-dependent transcriptional activation by association of p300 with STAT3 upon IL-6 stimulation. FEBS Lett. 495:71-76. http://dx.doi.org/10.1016/S0014-5793(01)02354-7.
20. Shi X, Zhang H, Paddon H, Lee G, Cao X, Pelech S. 2006. Phosphorylation of STAT3 serine-727 by cyclin-dependent kinase 1 is critical for nocodazole-induced mitotic arrest. Biochemistry 45:5857-5867. http://dx.doi.org/10.1021/bi052490j.
21. Chung J, Uchida E, Grammer TC, Blenis J. 1997. STAT3 serine phosphorylation by ERK-dependent and -independent pathways negatively modulates its tyrosine phosphorylation. Mol. Cell. Biol. 17:6508-6516.
22. Aziz MH, Manoharan HT, Church DR, Dreckschmidt NE, Zhong W, Oberley TD, Wilding G, Verma AK. 2007. Protein kinase C epsilon interacts with signal transducers and activators of transcription 3 (Stat3), phosphorylates Stat3 Ser727, and regulates its constitutive activation in prostate cancer. Cancer Res. 67:8828-8838. http://dx.doi.org/10.1158/0008-5472.CAN-07-1604.
23. Lee J-L, Wang M-J, Chen J-Y. 2009. Acetylation and activation of STAT3 mediated by nuclear translocation of CD44. J. Cell Biol. 185:949-957. http://dx.doi.org/10.1083/jcb.200812060.
24. Prabakaran S, Lippens G, Steen H, Gunawardena J. 2012. Posttranslational modification: nature's escape from genetic imprisonment and the basis for dynamic information encoding. Wiley Interdiscip. Rev. Syst. Biol. Med. 4:565-583. http://dx.doi.org/10.1002/wsbm.1185.
25. Waitkus MS, Chandrasekharan UM, Willard B, Haque SJ, DiCorleto PE. 2013. STAT3-mediated coincidence detection regulates noncanonical immediate early gene induction. J. Biol. Chem. 288:11988-12003. http://dx.doi.org/10.1074/jbc.M112.428516.
26. Sutherland C. 2011. What are the bona fide GSK3 substrates? Int. J. Alzheimers Dis. 2011:505607. http://dx.doi.org/10.4061/2011/505607.
27. Dephoure N, Zhou C, Villén J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP. 2008. A quantitative atlas of mitotic phosphorylation. Proc. Natl. Acad. Sci. U. S. A. 105:10762-10767. http://dx.doi.org/10.1073/pnas.0805139105.
28. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Körner R, Greff Z, Kéri G, Stemmann O, Mann M. 2008. Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol. Cell 31:438-448. http://dx.doi.org/10.1016/j.molcel.2008.07.007.
29. Hoffert JD, Pisitkun T, Wang G, Shen R-F, Knepper MA. 2006. Quantitative phosphoproteomics of vasopressin-sensitive renal cells: regulation of aquaporin-2 phosphorylation at two sites. Proc. Natl. Acad. Sci. U. S. A. 103:7159-7164. http://dx.doi.org/10.1073/pnas.0600895103.
30. DiCorleto PE, de la Motte CA. 1989. Thrombin causes increased monocytic-cell adhesion to endothelial cells through a protein kinase C-dependent pathway. Biochem. J. 264:71-77.
31. Liu H, Ma Y, Cole SM, Zander C, Chen K-H, Karras J, Pope RM. 2003. Serine phosphorylation of STAT3 is essential for Mcl-1 expression and macrophage survival. Blood 102:344-352. http://dx.doi.org/10.1182/blood-2002-11-3396.
32. Horiguchi A, Asano T, Kuroda K, Sato A, Asakuma J, Ito K, Hayakawa M, Sumitomo M. 2010. STAT3 inhibitor WP1066 as a novel therapeutic agent for renal cell carcinoma. Br. J. Cancer 102:1592-1599. http://dx.doi.org/10.1038/sj.bjc.6605691.
33. Xin H, Zhang C, Herrmann A, Du Y, Figlin R, Yu H. 2009. Sunitinib inhibition of Stat3 induces renal cell carcinoma tumor cell apoptosis and reduces immunosuppressive cells. Cancer Res. 69:2506-2513. http://dx.doi.org/10.1158/0008-5472.CAN-08-4323.
34. Bilim V, Ougolkov A, Yuuki K, Naito S, Kawazoe H, Muto A, Oya M, Billadeau D, Motoyama T, Tomita Y. 2009. Glycogen synthase kinase-3: a new therapeutic target in renal cell carcinoma. Br. J. Cancer 101:2005-2014. http://dx.doi.org/10.1038/sj.bjc.6605437.
35. Kawazoe H, Bilim VN, Ugolkov AV, Yuuki K, Naito S, Nagaoka A, Kato T, Tomita Y. 2012. GSK-3 inhibition in vitro and in vivo enhances antitumor effect of sorafenib in renal cell carcinoma (RCC). Biochem. Biophys. Res. Commun. 423:490-495. http://dx.doi.org/10.1016/j.bbrc.2012.05.147.
36. Yang J, Liao X, Agarwal MK, Barnes L, Auron PE, Stark GR. 2007. Unphosphorylated STAT3 accumulates in response to IL-6 and activates transcription by binding to NFkappaB. Genes Dev. 21:1396-1408. http://dx.doi.org/10.1101/gad.1553707.
37. Timofeeva OA, Chasovskikh S, Lonskaya I, Tarasova NI, Khavrutskii L, Tarasov SG, Zhang X, Korostyshevskiy VR, Cheema A, Zhang L, Dakshanamurthy S, Brown ML, Dritschilo A. 2012. Mechanisms of unphosphorylated STAT3 transcription factor binding to DNA. J. Biol. Chem. 287:14192-14200. http://dx.doi.org/10.1074/jbc.M111.323899.
38. Braunstein J, Brutsaert S, Olson R, Schindler C. 2003. STATs dimerize in the absence of phosphorylation. J. Biol. Chem. 278:34133-34140. http://dx.doi.org/10.1074/jbc.M304531200.
39. Yang J, Stark GR. 2008. Roles of unphosphorylated STATs in signaling. Cell Res. 18:443-451. http://dx.doi.org/10.1038/cr.2008.41.
40. Yang J, Chatterjee-Kishore M, Staugaitis SM, Nguyen H, Schlessinger K, Levy DE, Stark GR. 2005. Novel roles of unphosphorylated STAT3 in oncogenesis and transcriptional regulation. Cancer Res. 65:939-947.
41. Qin HR, Kim H-J, Kim J-Y, Hurt EM, Klarmann GJ, Kawasaki BT, Duhagon Serrat MA, Farrar WL. 2008. Activation of signal transducer and activator of transcription 3 through a phosphomimetic serine 727 promotes prostate tumorigenesis independent of tyrosine 705 phosphorylation. Cancer Res. 68:7736-7741. http://dx.doi.org/10.1158/0008-5472.CAN-08-1125.
42. Hazan-Halevy I, Harris D, Liu Z, Liu J, Li P, Chen X, Shanker S, Ferrajoli A, Keating MJ, Estrov Z. 2010. STAT3 is constitutively phosphorylated on serine 727 residues, binds DNA, and activates transcription in CLL cells. Blood 115:2852-2863. http://dx.doi.org/10.1182/blood-2009-10-230060.
43. Ng S-L, Friedman BA, Schmid S, Gertz J, Myers RM, Tenoever BR, Maniatis T. 2011. I B kinase epsilon (IKK(epsilon)) regulates the balance between type I and type II interferon responses. Proc. Natl. Acad. Sci. U. S. A. 108:21170-21175. http://dx.doi.org/10.1073/pnas.1119137109.
44. Tenoever BR, Ng S-L, Chua MA, McWhirter SM, García-Sastre A, Maniatis T. 2007. Multiple functions of the IKK-related kinase IKKepsilon in interferon-mediated antiviral immunity. Science 315:1274-1278. http://dx.doi.org/10.1126/science.1136567.
45. Nkansah E, Shah R, Collie GW, Parkinson GN, Palmer J, Rahman KM, Bui TT, Drake AF, Husby J, Neidle S, Zinzalla G, Thurston DE, Wilderspin AF. 2013. Observation of unphosphorylated STAT3 core protein binding to target dsDNA by PEMSA and X-ray crystallography. FEBS Lett. 587:833-839. http://dx.doi.org/10.1016/j.febslet.2013.01.065.
46. Schiavone D, Avalle L, Dewilde S, Poli V. 2011. The immediate early genes Fos and Egr1 become STAT1 transcriptional targets in the absence of STAT3. FEBS Lett. 585:2455-2460. http://dx.doi.org/10.1016/j.febslet.2011.06.020.
47. Becker S, Groner B, Mu CW. 1998. Three-dimensional structure of the Stat3 NL homodimer bound to DNA 394:145-151.
48. Tamaskar I, Garcia JA, Elson P, Wood L, Mekhail T, Dreicer R, Rini BI, Bukowski RM. 2008. Antitumor effects of sunitinib or sorafenib in patients with metastatic renal cell carcinoma who received prior antiangiogenic therapy. J. Urol. 179:81-86. http://dx.doi.org/10.1016/j.juro.2007.08.127.
49. Chang YS, Adnane J, Trail PA, Levy J, Henderson A, Xue D, Bortolon E, Ichetovkin M, Chen C, McNabola A, Wilkie D, Carter CA, Taylor IC, Lynch M, Wilhelm S. 2007. Sorafenib (BAY 43-9006) inhibits tumor growth and vascularization and induces tumor apoptosis and hypoxia in RCC xenograft models. Cancer Chemother. Pharmacol. 59:561-574. http://dx.doi.org/10.1007/s00280-006-0393-4.
50. Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, Negrier S, Chevreau C, Solska E, Desai AA, Rolland F, Demkow T, Hutson TE, Gore M, Freeman S, Schwartz B, Shan M, Simantov R, Bukowski RM. 2007. Sorafenib in advanced clear-cell renal-cell carcinoma. N. Engl. J. Med. 356:125-134. http://dx.doi.org/10.1056/NEJMoa060655.
51. Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, Oudard S, Negrier S, Szczylik C, Kim ST, Chen I, Bycott PW, Baum CM, Figlin RA. 2007. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N. Engl. J. Med. 356:115-124. http://dx.doi.org/10.1056/NEJMoa065044.
52. Najjar YG, Rini BI. 2012. Novel agents in renal carcinoma: a reality check. Ther. Adv. Med. Oncol. 4:183-194. http://dx.doi.org/10.1177/1758834012443725.
53. Guo C, Yang G, Khun K, Kong X, Levy D, Lee P, Melamed J. 2009. Activation of Stat3 in renal tumors. Am. J. Transl. Res. 1:283-290.
54. Gough DJ, Corlett A, Schlessinger K, Wegrzyn J, Larner AC, Levy DE. 2009. Mitochondrial STAT3 supports Ras-dependent oncogenic transformation. Science 324:1713-1716. http://dx.doi.org/10.1126/science.1171721.