Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

Complex roles of Stat1 in regulating gene expression

Abstract

Stat1 is a fascinating and complex protein with multiple, yet contrasting transcriptional functions. Upon activation, it drives the expression of many genes but also suppresses the transcription of others. These opposing characteristics also apply to its role in facilitating crosstalk between signal transduction pathways, as it participates in both synergistic activation and inhibition of gene expression. Stat1 is a functional transcription factor even in the absence of inducer-mediated activation, participating in the constitutive expression of some genes. This review summarizes the well studied involvement of Stat1 in IFN-dependent and growth factor-dependent signaling and then describes the roles of Stat1 in positive, negative and constitutive regulation of gene expression as well as its participation in crosstalk between signal transduction pathways.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  • Abril E, Real LM, Serrano A, Jimenez P, Garcia A, Canton J, Trigo I, Garrido F and Ruiz-Cabello F . 1998 Cancer Immunol Immunother 47: 113–120

  • Ala-aho R, Johansson N, Grenman R, Fusenig NE, Foschi M, Lopez-Otin C and Kahari VM . 2000 Oncogene 19: 248–257

  • Ashizawa K, Yamashita S, Nagayama Y, Kimura H, Hirayu H, Izumi M and Nagataki S . 1989 J Clin Endocrinol Metab 69: 475–477

  • Bach EA, Tanner JW, Marsters S, Ashkenazi A, Aguet M, Shaw AS and Schreiber RD . 1996 Mol Cell Biol 16: 3214–3221

  • Becker S, Groner B and Muller CW . 1998 Nature 394: 145–151

  • Bennett MR, Evan GI and Newby AC . 1994 Circ Res 74: 525–536

  • Bhattacharya S, Eckner R, Grossman S, Oldread E, Arany Z, D'Andrea A and Livingston DM . 1996 Nature 383: 344–347

  • Bluyssen HAR, Muzaffar R, Vlieststra RJ, van der Made ACJ, Leung S, Stark GR, Kerr IM, Trapman J and Levy DE . 1995 Proc Natl Acad Sci USA 92: 5645–5649

  • Bluyssen HA and Levy DE . 1997 J Biol Chem 272: 4600–4605

  • Boehm U, Guethlein L, Klamp T, Ozbek K, Schaub A, Futterer A, Pfeffer K and Howard JC . 1998 J Immunol 161: 6715–6723

  • Bromberg JF, Horvath CM, Wen Z, Schreiber RD and Darnell Jr JE . 1996 Proc Natl Acad Sci USA 93: 7673–7678

  • Chatterjee-Kishore M, Kishore R, Hicklin DJ, Marincola FM and Ferrone S . 1998 JBiol Chem 273: 16177–16183

  • Chelbi-Alix MK and Pelicano L . 1999 Leukemia 13: 1167–1174

  • Chen X, Vinkemeier U, Zhao Y, Jeruzalmi D, Darnell Jr JE and Kuriyan J . 1998 Cell 93: 827–839

  • Chin YE, Kitagawa M, Su WC, You ZH, Iwamoto Y and Fu XY . 1996 Science 272: 719–722

  • Colamonici OR, Uyttendaele H, Domanski P, Yan H and Krolewski JJ . 1994 J Biol Chem 269: 3518–3522

  • Dale TC, Rosen JM, Guille MJ, Lewin AR, Porter AGC, Kerr IM and Stark GR . 1989 EMBO J 8: 831–839

  • Darnell Jr JE, Kerr IM and Stark GR . 1994 Science 264: 1415–1421

  • David M, Romero G, Zhang ZY, Dixon JE and Larner AC . 1993 J Biol Chem 268: 6593–6599

  • Der SD, Zhou A, Williams BR and Silverman RH . 1998 Proc Natl Acad Sci USA 95: 15623–15628

  • Durbin JE, Hackenmiller R, Simon MC and Levy DE . 1996 Cell 84: 443–450

  • Endo TA, Masuhara M, Yokouchi M, Suzuki R, Sakamoto H, Mitsui K, Matsumoto A, Tanimura S, Ohtsubo M, Misawa H, Miyazaki T, Leonor N, Taniguchi T, Fujita T, Kanakura Y, Komiya S and Yoshimura A . 1997 Nature 387: 921–924

  • Fambrough D, McClure K, Kazlauskas A and Lander ES . 1999 Cell 97: 727–741

  • Felsher DW and Bishop, JM . 1999 Proc Natl Acad Sci USA 96: 3940–3944

  • Gao J, Morrison DC, Parmely TJ, Russell SW and Murphy WJ . 1997 J Biol Chem 272: 1226–1230

  • Gauzzi MC, Velazquez L, McKendry R, Mogensen KE, Fellous M and Pellegrini S . 1996 J Biol Chem 271: 20494–20500

  • Gollob JA, Schnipper CP, Murphy EA, Ritz J and Frank DA . 1999 J Immunol 162: 4472–4481.

  • Greenlund AC, Farrar MA, Viviano BL and Schreiber RD . 1994 EMBO J 13: 1591–1600

  • Greenlund AC, Morales MO, Viviano BL, Yan H, Krolewski J and Schreiber RD . 1995 Immunity 2: 677–687

  • Gouilleux-Gruart V, Gouilleux F, Desaint C, Claisse JF, Capoid JC, Delobel J, Weber-Nordt R, Dusanter-Fourt I, Dreyfus F, Groner B and Prin L . 1996 Blood 87: 1692–1697

  • Guschin D, Rogers N, Briscoe J, Witthuhn B, Watling D, Horn F, Pellegrini S, Yasukawa K, Heinrich P, Stark GR, Ihle JN and Kerr IM . 1995 EMBO J 14: 1421–1429

  • Han Y, Leaman DW, Watling D, Rogers NC, Groner B, Kerr IM, Wood WI and Stark GR . 1996 J Biol Chem 271: 5947–5952

  • Han Y, Watling DW, Rogers NC and Stark GR . 1997 Mol Endocrinol 11: 1180–1188

  • Haque SJ, Wu Q, Kammer W, Friedrich K, Smith JM, Kerr IM, Stark GR and Williams BR . 1997 Proc Natl Acad Sci USA 94: 8563–8568

  • Haspel RL and Darnell Jr JE . 1999 Proc Natl Acad Sci USA 96: 10188–10193

  • Haspel RL, Salditt-Georgieff M and Darnell Jr JE . 1996 EMBO J 15: 6262–6268

  • Horvai AE, Xu L, Korzus E, Brard G, Kalafus D, Mullen TM, Rose DW, Rosenfeld MG and Glass CK . 1997 Proc Natl Acad Sci USA 94: 1074–1079

  • Horvath CM, Wen Z and Darnell Jr JE . 1995 Genes Dev 9: 984–994

  • Horvath CM, Stark GR, Kerr IM, Darnell Jr JE . 1996 Mol Cell Biol 16: 6957–6964

  • Igarashi K, Garotta G, Ozmen L, Ziemiecki A, Wilks AF, Harpur AG, Larner AC and Finbloom DS . 1994 J Biol Chem 269: 14333–14336

  • IkedaY, Takeuchi K, Kato T, Taniyama Y, Sato K, Takahashi N, Sugawara A and Ito S . 1999 Biochem Biophys Res Commun 262: 494–498

  • Illa I, Gallardo E, Gimeno R, Serrano C, Ferrer I and Juarez C . 1997 Am J Pathol 151: 81–88

  • Imam AMA, Ackrill AM, Dale TC, Kerr IM and Stark GR . 1990 Nucleic Acids Res 18: 6573–6580

  • Iozzo RV, Cohen IR, Grassel S and Murdoch AD . 1994 Biochem J 302: 625–639

  • John J, McKendry R, Pellegrini S, Flavell D, Kerr IM and Stark GR . 1991 Mol Cell Biol 11: 4189–4195

  • Johnson LR, McCormack SA, Yang CH, Pfeffer SR and Pfeffer LM . 1999 Am J Physiol 276: C419–C425

  • Kaplan DH, Greenlund AC, Tanner JW, Shaw AS and Schreiber RD . 1996 J Biol Chem 271: 9–12

  • Kaplan DH, Shankaran V, Dighe AS, Stockert E, Aguet M, Old LJ and Schreiber RD . 1998 Proc Natl Acad Sci USA 95: 7556–7561

  • Kim TK and Maniatis T . 1996 Science 273: 1717–1719

  • Kominsky S, Johnson HM, Bryan G, Tanabe T, Hobeika AC, Subramaniam PS and Torres B . 1998 Oncogene 17: 2973–2979

  • Korzus E, Nagase H, Rydell R and Travis J . 1997 J Biol Chem 272: 1188–1196

  • Korzus E, Torchia J, Rose DW, Xu L, Kurokawa R, McInerney EM, Mullen TM, Glass CK and Rosenfeld MG . 1998 Science 279: 703–707

  • Kotenko SV, Izotova LS, Pollack BP, Mariano TM, Donnelly RJ, Muthukumaran G, Cook JR, Garotta G, Silvennoinen O, Ihle JN and Pestka S . 1995 J Biol Chem 270: 20915–20921

  • Kovarik P, Stoiber D, Novy M and Decker T . 1998 EMBO J 17: 3660–3668

  • Kovarik P, Stoiber D, Eyers PA, Menghini R, Neininger A, Gaestel M, Cohen P and Decker T . 1999 Proc Natl Acad Sci USA 96: 13956–13961

  • Krishnan K, Yan H, Lim JTE and Krolewski JJ . 1996 Oncogene 13: 125–133

  • Kumar A, Commane M, Flickinger TW, Horvath CM and Stark GR . 1997 Science 278: 1630–1632

  • Kung AWC and Lau KS . 1998 J Mol Endocrinol 20: 293–298

  • Lackmann M, Harpur AG, Oates AC, Mann RJ, Gabriel A, Meutermans W, Alewood PF, Kerr IM, Stark GR and Wilks AF . 1998 Growth Factors 16: 39–51

  • Leaman DW, Leung S, Li X and Stark GR . 1996a FASEB J 10: 1578–1588

  • Leaman DW, Pisharody S, Flickinger TW, Commane MA, Schlessinger J, Kerr IM, Levy DE and Stark GR . 1996b Mol Cell Biol 16: 369–375

  • Lee CK, Gimeno R and Levy DE . 1999 J Exp Med 190: 1451–1463

  • Lee CK, Smith E, Gimeno R, Gertner R and Levy DE . 2000 J Immunol 164: 1286–1292

  • Lewis M, Amento EP and Unemori EN . 1999 J Cell Biochem 72: 373–386

  • Li X, Leung S, Qureshi S, Darnell Jr JE and Stark GR . 1996 J Biol Chem 271: 5790–5794

  • Li X, Leung S, Burns C and Stark GR . 1998 Biochimie 80: 703–710

  • Look DC, Pelletier MR, Tidwell RM, Roswit WT and Holtzman MJ . 1995 J Biol Chem 270: 30264–30267

  • Melamed D, Tiefenbrun N, Yarden A and Kimchi A . 1993 Mol Cell Biol 13: 5255–5265

  • Meraz MA, White JM, Sheehan KCF, Bach EA, Rodig SJ, Dighe AS, Kaplan DH, Riley JK, Greenlund AC, Campbell D, Carver-Moore K, DuBois RN, Clark R, Aguet, M and Schreiber RD . 1996 Cell 84: 431–442

  • Min W, Pober JS and Johnson DR . 1996 J Immunol 156: 3174–3183

  • Min W, Pober JS and Johnson DR . 1998 Circ Res 83: 815–823

  • Miyazaki A, Shimura H, Endo T, Haraguchi K and Onaya T . 1999 Endocrinology 140: 4214–4220

  • Ogbourne S and Antalis TM . 1998 Biochem J 331: 1–14

  • Ohe K, Ikuyama S, Takayanagi R, Kohn LD and Nawata H . 1996 Mol Endocrinol 10: 826–836

  • Ohmori Y and Hamilton TA . 1994 J Immunol 153: 2204–2212

  • Ohmori Y, Schreiber RD and Hamilton TA . 1997 J Biol Chem 272: 14899–14907

  • Ouchi T, Lee SW, Ouchi M, Aaronson SA and Horvath CM . 2000 Proc Natl Acad Sci USA in press

  • Pine R . 1997 Nucleic Acids Res 25: 4346–4354

  • Qin H, Moellinger JD, Wells A, Windsor LJ, Sun Y, Benveniste EN . 1998 J Immunol 16: 6664–6673

  • Qureshi SA, Salditt-Georgieff M and Darnell Jr JE . 1995 Proc Natl Acad Sci USA 92: 3829–3833

  • Ramana, CV, Grammatikakis N, Chernov M, Nguyen H, Goh KC, Williams BRG and Stark GR . 2000 EMBO J 19: 263–272

  • Richer JK, Lange CA, Manning NG, Owen G, Powell R and Horwitz KB . 1998 J Biol Chem 273: 31317–31326

  • Sachsenmaier C, Sadowski HB and Cooper JA . 1999 Oncogene 18: 3583–3592

  • Sakatsume M, Igarashi K, Winestock KD, Garotta G, Larner AC and Finbloom DS . 1995 J Biol Chem 270: 17528–17534

  • Sampath D, Castro M, Look DC and Holtzman MJ . 1999 J Clin Invest 103: 1353–1361

  • Schindler C, Shuai K, Prezioso VR and Darnell Jr JE . 1992 Science 257: 809–813

  • Schindler C and Darnell Jr JE . 1995 Annu Rev Biochem 64: 621–651

  • Sekimoto T, Nakajima K, Tachibana T, Hirano T and Yoneda Y . 1997 J Biol Chem 271: 31017–31020

  • Sharma B and Iozzo RV . 1998 J Biol Chem 273: 4642–4646

  • Shikama N, Lyon J, La Thangue NB . 1997 Trends Cell Biol 7: 230–236

  • Shimoda K, Feng J, Murakami H, Nagata S, Watling D, Rogers NC, Stark GR, Kerr IM and Ihle JN . 1997 Blood 90: 597–604

  • Shuai K, Schindler C, Prezioso VR and Darnell Jr JE . 1992 Science 258: 1808–1812

  • Shuai K, Stark GR, Kerr IM and Darnell Jr JE . 1993 Science 261: 1744–1746

  • Sibinga NE, Wang H, Perrella MA, Endege WO, Patterson C, Yoshizumi M, Haber E and Lee ME . 1999 J Biol Chem 274: 12139–12146

  • Silvennoinen O, Schindler C, Schlessinger J and Levy DE . 1993 Science 261: 1736–1739

  • Stancato LF, David M, Carter-Su C, Larner AC and Pratt WB . 1996 J Biol Chem 271: 4134–4137

  • Stark GR, Kerr IM, Williams BR, Silverman RH and Schreiber RD . 1998 Annu Rev Biochem 67: 227–264

  • Starr R, Willson TA, Viney EM, Murray LJ, Rayner JR, Jenkins BJ, Gonda TJ, Alexander WS, Metcalf D, Nicola NA and Hilton DJ . 1997 Nature 387: 917–921

  • Sun WH, Pabon C, Alsayed Y, Huang PP, Jandeska S, Uddin S, Platanias LC and Rosen ST . 1998 Blood 91: 570–576

  • Takaoka A, Tanaka N, Mitani Y, Miyazaki T, Fujii H, Sato M, Kovarik P, Decker T, Schlessinger J and Taniguchi T . 1999 EMBO J 18: 2480–2488

  • Tamai K, Li K, Silos S, Rudnicka L, Hashimoto T, Nishikawa T and Uitto J . 1995 J Biol Chem 270: 392–396

  • Tannenbaum CS, Major JA and Hamilton TA . 1993 J Immunol 151: 6833–6839

  • Tiefenbrun N, Melamed D, Levy N, Resnitzky D, Hoffman I, Reed SI and Kimchi A . 1996 Mol Cell Biol 16: 3934–3944

  • Torchia J, Glass C and Rosenfeld MG . 1998 Curr Opin Cell Biol 10: 373–383

  • Ulloa L, Doody J and Massague J . 1999 Nature 397: 710–713

  • Vairo G, Vadiveloo PK, Royston AK, Rockman SP, Rock CO, Jackowski S and Hamilton JA . 1995 Oncogene 10: 1969–1976

  • Venkataraman C, Leung S, Salvekar A, Mano H and Schindler U . 1999 J Immunol 162: 4053–4061

  • Vignais ML, Sadowski HB, Watling D, Rogers NC and Gilman M . 1996 Mol Cell Biol 16: 1759–1769

  • Vignais ML and Gilman M . 1999 Mol Cell Biol 19: 3727–3735

  • Vinkemeier U, Cohen SL, Moarefi I, Chait BT, Kuriyan J and Darnell Jr JE . 1996 EMBO J 15: 5616–5626

  • Vinkemeier U, Moarefi I, Darnell Jr JE and Kuriyan J . 1998 Science 279: 1048–1052

  • Weber-Nordt RM, Egen C, Wehinger J, Ludwig W, Gouilleux-Gruart V, Mertelsmann R and Finke J . 1996 Blood 88: 809–816

  • Wen Z, Zhong Z and Darnell Jr JE . 1995 Cell 82: 241–250

  • Westermarck J and Kahari VM . 1999 FASEB J 13: 781–792

  • White LC, Wright KL, Felix NJ, Ruffner H, Reis LF, Pine R and Ting JP . 1996 Immunity 5: 365–376

  • Wong LH, Krauer KG, Hatzinisiriou I, Estcourt MJ, Hersey P, Tam ND, Edmondson S, Devenish RJ and Ralph SJ . 1997 J Biol Chem 272: 28779–28785

  • Xu X, Sun YL and Hoey T . 1996 Science 273: 794–797

  • Yie J, Senger K and Thanos D . 1999 Proc Natl Acad Sci USA 96: 13108–13113

  • You M, Yu DH and Feng GS . 1999 Mol Cell Biol 19: 2416–2424

  • Yuan W, Yufit T, Li L, Mori Y, Chen SJ and Varga J . 1999 J Cell Physiol 179: 97–108

  • Zhang JJ, Vinkemeier U, Gu W, Chakravarti D, Horvath CM and Darnell Jr JE . 1996 Proc Natl Acad Sci USA 93: 15092–15096

  • Zhang JJ, Zhao Y, Chait BT, Lathem WW, Ritzi M, Knippers R and Darnell Jr JE . 1998 EMBO J 17: 6963–6971

  • Zhu M, John S, Berg M and Leonard WJ . 1999 Cell 96: 121–130

  • Zhu X, Wen Z, Xu LZ and Darnell Jr JE . 1997 Mol Cell Biol 17: 6618–6623

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ramana, C., Chatterjee-Kishore, M., Nguyen, H. et al. Complex roles of Stat1 in regulating gene expression. Oncogene 19, 2619–2627 (2000). https://doi.org/10.1038/sj.onc.1203525

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1203525

Keywords

This article is cited by

Search

Quick links