Transforming Growth Factor β/Smad3 Signaling Regulates IRF-7 Function and Transcriptional Activation of the Beta Interferon Promoter

REFERENCES

• Alliston, T., Choy L., Ducy P., Karsenty G., and Derynck R.. 2001. TGF-β-induced repression of CBFA1 by Smad3 decreases cbfa1 and osteocalcin expression and inhibits osteoblast differentiation. EMBO J. 20:2254–2272.
   PubMed Web of Science ®Google Scholar
• Arteaga, C. L., Coffey R. J., Jr., Dugger T. C., McCutchen C. M., Moses H. L., and Lyons R. M.. 1990. Growth stimulation of human breast cancer cells with anti-transforming growth factor β antibodies: evidence for negative autocrine regulation by transforming growth factor β. Cell Growth Differ. 1:367–374.
   PubMedGoogle Scholar
• Au, W. C., Yeow W. S., and Pitha P. M.. 2001. Analysis of functional domains of IFN regulatory factor 7 and its association with IRF-3. Virology 280:273–282.
   PubMedGoogle Scholar
• Ausubel, F. M., Brent R. E., Kingston R. E., Moore D. D., Seidman J. G., Smith J. A., and Struhl K.. 1994. Current protocols in molecular biology. John Wiley and Sons, New York, N.Y.
   Google Scholar
• Chacko, B. M., Qin B., Correia J. J., Lam S. S., de Caestecker M. P., and Lin K.. 2001. The L3 loop and C-terminal phosphorylation jointly define Smad protein trimerization. Nat. Struct. Biol. 8:248–253.
   PubMedGoogle Scholar
• Chen, R. H., Ebner R., and Derynck R.. 1993. Inactivation of the type II receptor reveals two receptor pathways for the diverse TGF-β activities. Science 260:1335–1338.
   PubMed Web of Science ®Google Scholar
• Choy, L., Skillington J., and Derynck R.. 2000. Roles of autocrine TGF-β receptor and Smad signaling in adipocyte differentiation. J. Cell Biol. 149:667–682.
   PubMed Web of Science ®Google Scholar
• Datta, P. K., Blake M. C., and Moses H. L.. 2000. Regulation of plasminogen activator inhibitor-1 expression by transforming growth factor-β-induced physical and functional interactions between Smads and Sp1. J. Biol. Chem. 275:40014–40019.
   PubMed Web of Science ®Google Scholar
• Datto, M. B., Frederick J. P., Pan L., Borton A. J., Zhuang Y., and Wang X.-F.. 1999. Targeted disruption of Smad3 reveals an essential role in transforming growth factor β-mediated signal transduction. Mol. Cell. Biol. 19:2495–2504.
   PubMed Web of Science ®Google Scholar
• DeMaeyer, E. and J. DeMaeyer-Guignard. 1988. Interferons and other regulatory cytokines. John Wiley and Sons, New York, N.Y.
   Google Scholar
• Derynck, R., and Feng X.-H.. 1997. TGF-β receptor signaling. Biochim. Biophys. Acta 1333:F105–F150.
   PubMed Web of Science ®Google Scholar
• Derynck, R., and Choy L.. 1998. Transforming growth factor-β and its receptors, p. 593–636. In Thompson A. (ed.), The cytokine handbook, 3rd ed. Academic Press, San Diego, Calif.
   Google Scholar
• Derynck, R., Zhang Y., and Feng X.-H.. 1998. Smads: transcriptional activators of TGF-β responses. Cell 95:737–740.
   PubMed Web of Science ®Google Scholar
• Derynck, R., Akhurst R. J., and Balmain A.. 2001. TGF-β signaling in tumor suppression and cancer progression. Nat. Genet. 29:117–129.
   PubMed Web of Science ®Google Scholar
• Diebold, S. S., Montoya M., Unger H., Alexopoulou L., Roy P., Haswell L. E., Al-Shamkhani A., Flavell R., Borrow P., and Reis e Sousa C.. 2003. Viral infection switches non-plasmacytoid dendritic cells into high IFN producers. Nature 424:324–328.
   PubMed Web of Science ®Google Scholar
• Du, W., and Maniatis T.. 1992. An ATF/CREB binding site is required for virus induction of the human IFN β gene. Proc. Natl. Acad. Sci. USA 89:2150–2154.
   PubMedGoogle Scholar
• Feng, X.-H., Filvaroff E. H., and Derynck R.. 1995. Transforming growth factor-β (TGF-β)-induced down-regulation of cyclin A expression requires a functional TGF-β receptor complex. Characterization of chimeric and truncated type I and type II receptors. J. Biol. Chem. 270:24237–24245.
   PubMed Web of Science ®Google Scholar
• Feng, X.-H., and Derynck R.. 1996. Ligand-independent activation of transforming growth factor (TGF) β signaling pathways by heteromeric cytoplasmic domains of TGF-β receptors. J. Biol. Chem. 271:13123–13129.
   PubMedGoogle Scholar
• Feng, X.-H., Zhang Y., Wu R. Y., and Derynck R.. 1998. The tumor suppressor Smad4/DPC4 and transcriptional adaptor CBP/p300 are coactivators for Smad3 in TGF-β-induced transcriptional activation. Genes Dev. 12:2153–2163.
   PubMedGoogle Scholar
• Feng, X.-H., Lin X., and Derynck R.. 2000. Smad2, Smad3 and Smad4 cooperate with Sp1 to induce p15Ink4B transcription in response to TGF-β. EMBO J. 19:5178–5193.
   PubMed Web of Science ®Google Scholar
• Fitzgerald, K. A., McWhirter S. M., Faia K. L., Rowe D. C., Latz E., Golenbock D. T., Coyle A. J., Liao S. M., and Maniatis T.. 2003. IKKε and TBK1 are essential components of the IRF3 signaling pathway. Nat. Immunol. 4:491–496.
   PubMed Web of Science ®Google Scholar
• Fujita, T., Miyamoto M., Kimura Y., Hammer J., and Taniguchi T.. 1989. Involvement of a cis-element that binds an H2TF-1/NFκB like factor(s) in the virus-induced IFN-β gene expression. Nucleic Acids Res. 17:3335–3346.
   PubMed Web of Science ®Google Scholar
• Gandrillon, O., Schmidt U., Beug H., and Samarut J.. 1999. TGF-β cooperates with TGF-α to induce the self-renewal of normal erythrocytic progenitors: evidence for an autocrine mechanism. EMBO J. 18:2764–2781.
   PubMedGoogle Scholar
• Gibellini, D., Zauli G., Re M. C., Milani D., Furlini G., Caramelli E., Capitani S., and La Placa M.. 1994. Recombinant human immunodeficiency virus type-1 (HIV-1) Tat protein sequentially up-regulates IL-6 and TGF-β1 mRNA expression and protein synthesis in peripheral blood monocytes. Br. J. Haematol. 88:261–267.
   PubMed Web of Science ®Google Scholar
• Grandvaux, N., tenOever B. R., Servant M. J., and Hiscott J.. 2002. The IFN antiviral response: from viral invasion to evasion. Curr. Opin. Infect. Dis. 15:259–267.
   PubMed Web of Science ®Google Scholar
• Gyuris, J., Golemis E., Chertkov H., and Brent R.. 1993. Cdi1, a human G1 and S phase protein phosphatase that associates with Cdk2. Cell 75:791–803.
   PubMed Web of Science ®Google Scholar
• Haagmans, B. L., Teerds K. J., van den Eijnden-van Raaij A. J., Horzinek M. C., and Schijns V. E.. 1997. Transforming growth factor β production during rat cytomegalovirus infection. J. Gen. Virol. 78:205–213.
   PubMedGoogle Scholar
• Hanai, J., Chen L. F., Kanno T., Ohtani-Fujita N., Kim W. Y., Guo W. H., Imamura T., Ishidou Y., Fukuchi M., Shi M. J., et al. 1999. Interaction and functional cooperation of PEBP2/CBF with Smads. Synergistic induction of the immunoglobulin germline Cα promoter. J. Biol. Chem. 274:31577–31582.
   PubMed Web of Science ®Google Scholar
• Hata, N., Sato M., Takaoka A., Asagiri M., Tanaka N., and Taniguchi T.. 2001. Constitutive IFN-α/β signal for efficient IFN-α/β gene induction by virus. Biochem. Biophys. Res. Commun. 285:518–525.
   PubMedGoogle Scholar
• Hu, R., Oyaizu N., Than S., Kalyanaraman V. S., Wang X. P., and Pahwa S.. 1996. HIV-1 gp160 induces transforming growth factor-β production in human PBMC. Clin. Immunol. Immunopathol. 80:283–289.
   PubMedGoogle Scholar
• Hua, X., Liu X., Ansari D. O., and Lodish H. F.. 1998. Synergistic cooperation of TFE3 and Smad proteins in TGF-β-induced transcription of the plasminogen activator inhibitor-1 gene. Genes Dev. 12:3084–3095.
   PubMed Web of Science ®Google Scholar
• Hua, X., Miller Z. A., Benchabane H., Wrana J. L., and Lodish H. F.. 2000. Synergism between transcription factors TFE3 and Smad3 in transforming growth factor-β-induced transcription of the Smad7 gene. J. Biol. Chem. 275:33205–33208.
   PubMed Web of Science ®Google Scholar
• Itoh, S., Itoh F., Goumans M. J., and Ten Dijke P.. 2000. Signaling of transforming growth factor-β family members through Smad proteins. Eur. J. Biochem. 267:6954–6967.
   PubMedGoogle Scholar
• Janknecht, R., Wells N. J., and Hunter T.. 1998. TGF-β-stimulated cooperation of Smad proteins with the coactivators CBP/p300. Genes Dev. 12:2114–2119.
   PubMedGoogle Scholar
• Juang, Y., Lowther W., Kellum M., Au W. C., Lin R., Hiscott J., and Pitha P. M.. 1998. Primary activation of IFN α and IFN β gene transcription by IFN regulatory factor 3. Proc. Natl. Acad. Sci. USA 95:9837–9842.
   PubMed Web of Science ®Google Scholar
• Kon, A., Vindevoghel L., Kouba D. J., Fujimura Y., Uitto J., and Mauviel A.. 1999. Cooperation between SMAD and NF-κB in growth factor regulated type VII collagen gene expression. Oncogene 18:1837–1844.
   PubMed Web of Science ®Google Scholar
• Labbé, E., Silvestri C., Hoodless P. A., Wrana J. L., and Attisano L.. 1998. Smad2 and Smad3 positively and negatively regulate TGF-β-dependent transcription through the forkhead DNA-binding protein FAST1/2. Mol. Cell 2:109–120.
   PubMed Web of Science ®Google Scholar
• Lenardo, M. J., Fan C. M., Maniatis T., and Baltimore D.. 1989. The involvement of NF-κB in β-IFN gene regulation reveals its role as widely inducible mediator of signal transduction. Cell 57:287–294.
   PubMed Web of Science ®Google Scholar
• Letterio, J. J., and Roberts A. B.. 1998. Regulation of immune responses by TGF-β. Annu. Rev. Immunol. 16:137–161.
   PubMed Web of Science ®Google Scholar
• Levy, D. E., and Darnell J. E., Jr. 2002. Stats: transcriptional control and biological impact. Nat. Rev. Mol. Cell. Biol. 3:651–662.
   PubMed Web of Science ®Google Scholar
• Levy, D. E., Marié I., Smith E., and Prakash A.. 2002. Enhancement and diversification of IFN induction by IRF-7-mediated positive feedback. J. Interferon Cytokine Res. 22:87–93.
   PubMed Web of Science ®Google Scholar
• Levy, D. E., Marié I., and Prakash A.. 2003. Ringing the IFN alarm: differential regulation of gene expression at the interface between innate and adaptive immunity. Curr. Opin. Immunol. 15:52–58.
   PubMed Web of Science ®Google Scholar
• Liberati, N. T., Datto M. B., Frederick J. P., Shen X., Wong C., Rougier-Chapman E. M., and Wang X.-F.. 1999. Smads bind directly to the Jun family of AP-1 transcription factors. Proc. Natl. Acad. Sci. USA 96:4844–4849.
   PubMed Web of Science ®Google Scholar
• Lin, R., Genin P., Mamane Y., and Hiscott J.. 2000. Selective DNA binding and association with the CREB binding protein coactivator contribute to differential activation of α/β IFN genes by IFN regulatory factors 3 and 7. Mol. Cell. Biol. 20:6342–6353.
   PubMed Web of Science ®Google Scholar
• Lin, R., Mamane Y., and Hiscott J.. 2000. Multiple regulatory domains control IRF-7 activity in response to virus infection. J. Biol. Chem. 275:34320–34327.
   PubMed Web of Science ®Google Scholar
• Lopez-Rovira, T., Chalaux E., Rosa J. L., Bartrons R., and Ventura F.. 2000. Interaction and functional cooperation of NF-κB with Smads. Transcriptional regulation of the JunB promoter. J. Biol. Chem. 275:28937–28946.
   PubMed Web of Science ®Google Scholar
• Maniatis, T., Falvo J. V., Kim T. H., Kim T. K., Lin C. H., Parekh B. S., and Wathelet M. G.. 1998. Structure and function of the IFN-β enhanceosome. Cold Spring Harbor Symp. Quant. Biol. 63:609–620.
   PubMedGoogle Scholar
• Marié, I., Durbin J. E., and Levy D. E.. 1998. Differential viral induction of distinct IFN-α genes by positive feedback through IFN regulatory factor-7. EMBO J. 17:6660–6669.
   PubMed Web of Science ®Google Scholar
• Marié, I., Smith E., Prakash A., and Levy D. E.. 2000. Phosphorylation-induced dimerization of IFN regulatory factor 7 unmasks DNA binding and a bipartite transactivation domain. Mol. Cell. Biol. 20:8803–8814.
   PubMed Web of Science ®Google Scholar
• Massagué, J. 2000. How cells read TGF-β signals. Nat. Rev. Mol. Cell. Biol. 1:169–178.
   PubMed Web of Science ®Google Scholar
• McCartney-Francis, N. L., Frazier-Jessen M., and Wahl S. M.. 1998. TGF-β: a balancing act. Int. Rev. Immunol. 16:553–580.
   PubMedGoogle Scholar
• McKiel, V., Gu Z., Wainberg M. A., and Hiscott J.. 1995. Inhibition of human immunodeficiency virus type 1 multiplication by transforming growth factor β1 and AZT in HIV-1-infected myeloid cells. J. Interferon Cytokine Res. 15:849–855.
   PubMedGoogle Scholar
• Michelson, S., Alcami J., Kim S. J., Danielpour D., Bachelerie F., Picard L., Bessia C., Paya C., and Virelizier J. L.. 1994. Human cytomegalovirus infection induces transcription and secretion of transforming growth factor β1. J. Virol. 68:5730–5737.
   PubMed Web of Science ®Google Scholar
• Mossalayi, M. D., Mentz F., Ouaaz F., Dalloul A. H., Blanc C., Debre P., and Ruscetti F. W.. 1995. Early human thymocyte proliferation is regulated by an externally controlled autocrine transforming growth factor-β1 mechanism. Blood 85:3594–3601.
   PubMedGoogle Scholar
• Moustakas, A., Souchelnytskyi S., and Heldin C.-H.. 2001. Smad regulation in TGF-β signal transduction. J. Cell Sci. 114:4359–4369.
   PubMed Web of Science ®Google Scholar
• Munshi, N., Yie Y., Merika M., Senger K., Lomvardas S., Agalioti T., and Thanos D.. 1999. The IFN-β enhancer: a paradigm for understanding activation and repression of inducible gene expression. Cold Spring Harbor Symp. Quant. Biol. 64:149–159.
   PubMedGoogle Scholar
• Pardali, E., Xie X. Q., Tsapogas P., Itoh S., Arvanitidis K., Heldin C. H., ten Dijke P., Grundström T., and Sideras P.. 2000. Smad and AML proteins synergistically confer transforming growth factor β1 responsiveness to human germ-line IgA genes. J. Biol. Chem. 275:3552–3560.
   PubMed Web of Science ®Google Scholar
• Pardali, K., Kurisaki A., Morén A., ten Dijke P., Kardassis D., and Moustakas A.. 2000. Role of Smad proteins and transcription factor Sp1 in p21Waf1/Cip1 regulation by transforming growth factor-β. J. Biol. Chem. 275:29244–29256.
   PubMed Web of Science ®Google Scholar
• Qin, B. Y., Liu C., Lam S. S., Srimath H., Delston R., Correia J. J., Derynck R., and Lin K.. 2003. Crystal structure of IRF-3 transactivation domain reveals mechanism of autoinhibition and virus-induced phospho-activation. Nat. Struct. Biol. 10:913–921.
   PubMedGoogle Scholar
• Qing, J., Zhang Y., and Derynck R.. 2000. Structural and functional characterization of the transforming growth factor-β-induced Smad3/c-Jun transcriptional cooperativity. J. Biol. Chem. 275:38802–38812.
   PubMed Web of Science ®Google Scholar
• Reed, S. G. 1999. TGF-β in infections and infectious diseases. Microbes Infect. 1:1313–1325.
   PubMed Web of Science ®Google Scholar
• Ryu, S., Zhou S., Ladurner A. G., and Tjian R.. 1999. The transcriptional cofactor complex CRSP is required for activity of the enhancer-binding protein Sp1. Nature 397:446–450.
   PubMed Web of Science ®Google Scholar
• Sano, Y., Harada J., Tashiro S., Gotoh-Mandeville R., Maekawa T., and Ishii S.. 1999. ATF-2 is a common nuclear target of Smad and TAK1 pathways in transforming growth factor-β signaling. J. Biol. Chem. 274:8949–8957.
   PubMed Web of Science ®Google Scholar
• Sato, M., Suemori H., Hata N., Asagiri M., Ogasawara K., Nakao K., Nakaya T., Katsuki M., Noguchi S., Tanaka N., and Taniguchi T.. 2000. Distinct and essential roles of transcription factors IRF-3 and IRF-7 in response to viruses for IFN-α/β gene induction. Immunity 13:539–548.
   PubMed Web of Science ®Google Scholar
• Schafer, S. L., Lin R., Moore P. A., Hiscott J., and Pitha P. M.. 1998. Regulation of type I IFN gene expression by IFN regulatory factor-3. J. Biol. Chem. 273:2714–2720.
   PubMed Web of Science ®Google Scholar
• Servant, M. J., tenOever B., and Lin R.. 2002. Overlapping and distinct mechanisms regulating IRF-3 and IRF-7 function. J. Interferon Cytokine Res. 22:49–58.
   PubMedGoogle Scholar
• Servant, M. J., Grandvaux N., and Hiscott J.. 2002. Multiple signaling pathways leading to the activation of IFN regulatory factor 3. Biochem. Pharmacol. 64:985–992.
   PubMedGoogle Scholar
• Sharma, S., tenOever B. R., Grandvaux N., Zhou G. P., Lin R., and Hiscott J. P.. 2003. Triggering the IFN antiviral response through a IKK-related pathway. Science 300:1148–1151.
   PubMed Web of Science ®Google Scholar
• Shen, X., Hu P. P., Liberati N. T., Datto M. B., Frederick J. P., and Wang X.-F.. 1998. TGF-β-induced phosphorylation of Smad3 regulates its interaction with coactivator p300/CREB-binding protein. Mol. Biol. Cell 9:3309–3319.
   PubMed Web of Science ®Google Scholar
• Shi, Y., Hata A., Lo R. S., Massagué J., and Pavletich N. P.. 1997. A structural basis for mutational inactivation of the tumour suppressor Smad4. Nature 388:87–93.
   PubMed Web of Science ®Google Scholar
• Shi, Y., and Massagué J.. 2003. Mechanisms of TGF-β signaling from cell membrane to the nucleus. Cell 113:685–700.
   PubMed Web of Science ®Google Scholar
• Shum, L., Reeves S. A., Kuo A., Fromer E. S., and Derynck R.. 1994. Association of the transmembrane transforming growth factor-α precursor with a protein kinase complex. J. Cell Biol. 125:903–916.
   PubMedGoogle Scholar
• Smith, E. J., Marié I., Prakash A., Carcia-Sastre A., and Levy D. E.. 2003. IRF-3 and IRF-7 phosphorylation in virus-infected cells does not require double stranded RNA-dependent protein kinase R or IκB kinase, but is blocked by vaccinia virus E3L protein. J. Biol. Chem. 23:8951–8957.
   Google Scholar
• Spaccapelo, R., Romani L., Tonnetti L., Cenci E., Mencacci A., Del Sero G., Tognellini R., Reed S. G., Puccetti P., and Bistoni F.. 1995. TGF-β is important in determining the in vivo patterns of susceptibility or resistance in mice infected with Candida albicans. J. Immunol. 155:1349–1360.
   PubMed Web of Science ®Google Scholar
• Stark, G. R., Kerr I. M., Williams B. R., Silverman R. H., and Schreiber R. D.. 1998. How cells respond to IFNs. Annu. Rev. Biochem. 67:227–264.
   PubMed Web of Science ®Google Scholar
• Taniguchi, T., Ogasawara K., Takaoka A., and Tanaka N.. 2001. IRF family of transcription factors as regulators of host defense. Annu. Rev. Immunol. 19:623–655.
   PubMed Web of Science ®Google Scholar
• Taniguchi, T., and Takaoka A.. 2001. A weak signal for strong responses: IFN-α/β revisited. Nat. Rev. Mol. Cell. Biol. 2:378–386.
   PubMed Web of Science ®Google Scholar
• Taniguchi, T., and Takaoka A.. 2002. The IFN-α/β system in antiviral responses: a multimodal machinery of gene regulation by the IRF family of transcription factors. Curr. Opin. Immunol. 14:111–116.
   PubMed Web of Science ®Google Scholar
• ten Dijke, P., Miyazono K., and Heldin C.-H.. 2000. Signaling inputs converge on nuclear effectors in TGF-β signaling. Trends Biochem. Sci. 25:64–70.
   PubMedGoogle Scholar
• Topper, J. N., DiChiara M. R., Brown J. D., Williams A. J., Falb D., Collins T., and Gimbrone M. A., Jr. 1998. CREB binding protein is a required coactivator for Smad-dependent, transforming growth factor β transcriptional responses in endothelial cells. Proc. Natl. Acad. Sci. USA 95:9506–9511. (Erratum, 95:12735.)
   PubMedGoogle Scholar
• Visvanathan, K. V., and Goodbourn S.. 1989. Double-stranded RNA activates binding of NF-κB to an inducible element in the human β-IFN promoter. EMBO J. 8:1129–1138.
   PubMed Web of Science ®Google Scholar
• Wakefield, L. M., and Roberts A. B.. 2002. TGF-β signaling: positive and negative effects on tumorigenesis. Curr. Opin. Genet. Dev. 12:22–29.
   PubMed Web of Science ®Google Scholar
• Wathelet, M. G., Lin C. H., Parekh B. S., Ronco L. V., Howley P. M., and Maniatis T.. 1998. Virus infection induces the assembly of coordinately activated transcription factors on the IFN-β enhancer in vivo. Mol. Cell 1:507–518.
   PubMed Web of Science ®Google Scholar
• Wong, C., Rougier-Chapman E. M., Frederick J. P., Datto M. B., Liberati N. T., Li J. M., and Wang X.-F.. 1999. Smad3-Smad4 and AP-1 complexes synergize in transcriptional activation of the c-Jun promoter by transforming growth factor β. Mol. Cell. Biol. 19:1821–1830.
   PubMedGoogle Scholar
• Wu, R. Y., Zhang Y., Feng X.-H., and Derynck R.. 1997. Heteromeric and homomeric interactions correlate with signaling activity and functional cooperativity of Smad3 and Smad4/DPC4. Mol. Cell. Biol. 17:2521–2528.
   PubMedGoogle Scholar
• Wu, S. P., Theodorescu D., Kerbel R. S., Willson J. K., Mulder K. M., Humphrey L. E., and Brattain M. G.. 1992. TGF-β1 is an autocrine-negative growth regulator of human colon carcinoma FET cells in vivo as revealed by transfection of an antisense expression vector. J. Cell Biol. 116:187–196.
   PubMed Web of Science ®Google Scholar
• Yang, H., Lin C. H., Ma G., Baffi M. O., and Wathelet M. G.. 2003. Interferon regulatory factor (IRF)-7 synergizes with other transcription factors through multiple interactions with p300/CBP coactivators. J. Biol. Chem. 278:15495–15504.
   PubMed Web of Science ®Google Scholar
• Yoneyama, M., Suhara W., Fukuhara Y., Sato M., Ozato K., and Fujita T.. 1996. Autocrine amplification of type I IFN gene expression mediated by IFN stimulated gene factor 3 (ISGF3). J. Biochem. (Tokyo) 120:160–169.
   PubMed Web of Science ®Google Scholar
• Yoneyama, M., Suhara W., Fukuhara Y., Fukuda M., Nishida E., and Fujita T.. 1998. Direct triggering of the type I IFN system by virus infection: activation of a transcription factor complex containing IRF-3 and CBP/p300. EMBO J. 17:1087–1095.
   PubMed Web of Science ®Google Scholar
• Yoneyama, M., Suhara W., and Fujita T.. 2002. Control of IRF-3 activation by phosphorylation. J. Interferon Cytokine Res. 22:73–76.
   PubMed Web of Science ®Google Scholar
• Yoo, Y. D., Chiou C. J., Choi K. S., Yi Y., Michelson S., Kim S., Hayward G. S., and Kim S. J.. 1996. The IE2 regulatory protein of human cytomegalovirus induces expression of the human transforming growth factor β1 gene through an Egr-1 binding site. J. Virol. 70:7062–7070.
   PubMedGoogle Scholar
• Yoo, Y. D., Ueda H., Park K., Flanders K. C., Lee Y. I., Jay G., and Kim S. J.. 1996. Regulation of transforming growth factor-β1 expression by the hepatitis B virus (HBV) X transactivator. Role in HBV pathogenesis. J. Clin. Investig. 97:388–395.
   PubMed Web of Science ®Google Scholar
• Zervos, A. S., Gyuris J., and Brent R.. 1993. Mxi1, a protein that specifically interacts with Max to bind Myc-Max recognition sites. Cell 72:223–232.
   PubMed Web of Science ®Google Scholar
• Zhang, L., and Pagano J. S.. 1997. IRF-7, a new IFN regulatory factor associated with Epstein-Barr virus latency. Mol. Cell. Biol. 17:5748–5757.
   PubMedGoogle Scholar
• Zhang, L., and Pagano J. S.. 2002. Structure and function of IRF-7. J. Interferon Cytokine Res. 22:95–101.
   PubMedGoogle Scholar
• Zhang, Y., Feng X., Wu R., and Derynck R.. 1996. Receptor-associated Mad homologues synergize as effectors of the TGF- β response. Nature 383:168–172.
   PubMed Web of Science ®Google Scholar
• Zhang, Y., Feng X. H., and Derynck R.. 1998. Smad3 and Smad4 cooperate with c-Jun/c-Fos to mediate TGF-β-induced transcription. Nature 394:909–913. (Erratum, 396:491, 1998.)
   PubMed Web of Science ®Google Scholar
• Zhang, Y., and Derynck R.. 1999. Regulation of Smad signalling by protein associations and signalling crosstalk. Trends Cell Biol. 9:274–279.
   PubMed Web of Science ®Google Scholar
• Zhang, Y., and Derynck R.. 2000. Transcriptional regulation of the transforming growth factor-β-inducible mouse germ line Igα constant region gene by functional cooperation of Smad, CREB, and AML family members. J. Biol. Chem. 275:16979–16985.
   PubMed Web of Science ®Google Scholar