Publications

Publications

Primary research papers

Cai X, Chen J, Xu H, Liu S, Jiang QX, Halfmann R, Chen ZJ. (2014) Prion-like Polymerization Underlies Signal Transduction in Antiviral Immune Defense and Inflammasome Activation. Cell156(6):1207-22.

Xu H, He X, Zheng H, Huang LJ, Hou F, Yu Z, de la Cruz MJ, Borkowski B, Zhang X, Chen ZJ, Jiang QX. (2014) Structural basis for the prion-like MAVS filaments in antiviral innate immunity. Elife. 3:e01489.

Zhang X, Wu J, Du F, Xu H, Sun L, Chen Z, Brautigam CA, Zhang X, Chen ZJ. (2014) The cytosolic DNA sensor cGAS forms an oligomeric complex with DNA and undergoes switch-like conformational changes in the activation loop. Cell Rep. 6(3):421-30. 

Li, X.D., Wu, J., Gao, D., Wang, H., Sun, L., and Chen, Z.J. (2013) Pivotal Roles of cGAS-cGAMP Signaling in Antiviral Defense and Immune Adjuvant Effects. Science 341(6152):1390-4.

Liu, S., Chen, J., Cai, X., Wu, J., Chen, X., Wu, Y-T., Sun, L., and Chen, Z.J. (2013) MAVS recruits multiple ubiquitin E3 ligases to activate antiviral signaling cascades. eLife 2:e00785.

Gao, D., Wu, J., Wu, Y-T., Du, F., Aroh, C., Yan, N., Sun, L., and Chen, Z.J. (2013) Cyclic GMP-AMP Synthase Is an Innate Immune Sensor of HIV and Other Retroviruses. Science 341:903-906.

Zhang, X., Shi, H., Wu, J., Zhang, X., Sun, L., Chen, C., and Chen, Z.J. (2013) Cyclic GMP-AMP containing mixed phosphodiester linkages is an endogenous high-affinity ligand for STING. Mol. Cell 51:226-235.

Sun, L., Wu, J., Du, F., Chen, X., and Chen, Z.J. (2012) Cyclic GMP-AMP Synthase Is a Cytosolic DNA Sensor That Activates the Type I Interferon Pathway. Science 339, 786-791.

Wu, J., Sun, L., Chen, X., Du, F., Shi, H., Chen, C., and Chen Z.J. (2012) Cyclic GMP-AMP Is an Endogenous Second Messenger in Innate Immune Signaling by Cytosolic DNA. Science 339, 826-830.

Li, X.D., and Chen, Z.J. (2012) Sequence specific detection of bacterial 23S ribosomal RNA by TLR13. Elife 1, e00102.

Jiang, X., Kinch, L., Brautigam, C.A., Chen, X., Du, F., Grishin, N., and Chen, Z.J. (2012) Ubiquitin-induced oligomerization of RIG-I and MDA5 activates antiviral innate immune response. Immunity 36, 959-973.

Tanaka, Y., and Chen, Z.J. (2012). STING Specifies IRF3 Phosphorylation by TBK1 in the Cytosolic DNA Signaling Pathway. Science Signaling 5, ra20.

Skaug, B., Chen, J., Du, F., He, J, Ma, A., and Chen, Z.J. (2011) Direct, non-catalytic mechanism of IKK inhibition by A20. Molecular Cell 44, 559-571.

Hou, F., Sun, L., Zheng, H., Skaug, B., Jiang, Q.X., and Chen, Z.J. (2011). MAVS Forms Functional Prion-like Aggregates to Activate and Propagate Antiviral Innate Immune Response. Cell 146, 448-461.

Li, X.D., Chiu, Y.H., Ismail, A.S., Behrendt, C.L., Wight-Carter, M., Hooper, L.V., and Chen, Z.J. (2011). Mitochondrial antiviral signaling protein (MAVS) monitors commensal bacteria and induces an immune response that prevents experimental colitis. Proc Natl Acad Sci USA 108, 17390-17395.

Zeng, W., Sun, L., Jiang, X., Chen, X., Hou, F., Adhikari, A., Xu, M., and Chen, Z.J. (2010) Reconstitution of the RIG-I pathway reveals a signaling role of unanchored polyubiquitin chains in innate immunity. Cell 141, 315-330.

Zhao, M., Li, X.D., and Chen, Z. J. (2010) CC2D1A, a DM14 and C2 domain protein, activates NF-kappaB through the canonical pathway. J Biol Chem 285, 24372-24380.

Zeng, W., Xu, M., Liu, S., Sun, L., Chen, Z.J. (2009) Key role of Ubc5 and K63 polyubiquitination in viral activation of IRF3. Molecular Cell 36, 302-314.

Xu, M., Skaug, B., Zeng, W., and Chen, Z.J. (2009) A ubiquitin replacement strategy reveals distinct mechanisms of IKK activation by TNFa and IL-1b. Molecular Cell 36, 315-325.

Xia, Z.P., Sun, L., Chen, X., Pineda, G., Jiang, X., Adhikari, A., Zeng, W., and Chen, Z.J. (2009). Direct activation of protein kinases by unanchored polyubiquitin chains. Nature 461, 114-119.

Chiu, Y.H., Macmillan, J.B., and Chen, Z.J. (2009). RNA polymerase III detects cytosolic DNA and induces type I interferons through the RIG-I pathway. Cell 138, 576-591.

Bhoj, V.G., Sun, Q., Bhoj, E., Somers, C., Chen, X., Torres, J-P., Mejias, A., Gomez., A., Jafri, H., Ramilo, O., Chen, Z.J. (2008). MAVS and MyD88 are essential for innate immunity but not cytotoxic T lymphocyte response against respiratory syncytial virus. Proc. Natl. Acad. Sci. USA 105, 14046-14051.

Chiu, Y-H., Sun, Q.,  and Chen, Z.J. (2007) E1-L2 activates both ubiquitin and FAT-10. Molecular Cell 27, 1014-1023.

Sun, Q., Sun, L., Liu, H-H., Chen, X., Seth, R.B., Forman, J. and Chen, Z.J. (2006) The specific and essential role of MAVS in antiviral innate immune responses. Immunity 24, 633-642.

Ea, C-K., Deng, L., Xia, Z-P., Pineda, G., and Chen, Z.J. (2006) Activation of IKK by TNFa requires site-specific ubiquitination of RIP1 and polyubiquitin binding by NEMO. Molecular Cell 22, 245-257.

Liu, H-H., Xie, M., Schneider, M.D., and Chen, Z.J. (2006) The essential role of TAK1 in thymocyte development and activation. Proc. Natl. Acad. Sci. USA 103, 11677-11682.

Li, X-D., Sun, L., Seth, R.B., Pineda, G., and Chen, Z.J. (2005) The Hepatitis C Virus Protease NS3/4A Cleaves MAVS off the Mitochondria to Evade Innate Immunity. Proc. Natl. Acad. Sci. USA 102, 17717-17722.

Seth, R.B., Sun, L., Ea, C., and Chen, Z.J. (2005) Identification and characterization of MAVS: a mitochondrial antiviral signaling protein that activates NF-kB and IRF3. Cell 122, 669-682.

Kanayama, A., Seth, R.B., Ea, C-K, Hong, M., Shaito, A., Deng, L., and Chen, Z.J. (2004) TAB2 and TAB3 activate the NF-kB pathway through binding to polyubiquitin chains. Molecular Cell 15, 535-548.

Sun, L., Deng, L., Ea, C-K., Xia, Z-P., and Chen, Z.J. (2004) The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes. Molecular Cell 14, 289-301.

Ea, C-K., Sun, L., Inoue, J-I, and Chen, Z.J. (2004) TIFA activates IKK by promoting the oligomerization and ubiquitin ligase activity of TRAF6. Proc. Natl. Acad. Sci. 101, 15318-15323.

Wang, C., Deng, L., Hong, M. Akkaraju, G.R., Inoue, J-i., and Chen, Z.J. (2001) TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature 412, 346-351.

Deng, L., Wang, C., Spencer, E., Yang, L., Braun, A., You, J., Slaughter, C., Pickart, C., and Chen, Z.J. (2000) Activation of the IkB kinase complex requires a dimeric ubiquitin conjugating enzyme complex and the formation of a unique polyubiquitin chain. Cell 103, 351-361.

Spencer, E., Jiang, J., and Chen, Z.J. (1999) Signal-induced ubiquitination of IkBa by the F-box protein, Slimb/b-TrCP. Genes & Dev. 13, 284-294.

Reviews and Previews

Chen J, Chen ZJ. (2013) Regulation of NF-κB by ubiquitination. Curr Opin Immunol. 25(1):4-12. 

Chen, Z.J. (2012). Ubiquitination in signaling to and activation of IKK. Immunol Rev 246, 95-106.

Yan, N., and Chen, Z.J. (2012). Intrinsic antiviral immunity. Nat Immunol 13, 214-222.

Jiang, X., and Chen, Z.J. (2012). The role of ubiquitylation in immune defence and pathogen evasion. Nat Rev Immunol 12, 35-48.

Jiang, Q.X., and Chen, Z.J. (2011). Structural insights into the activation of RIG-I, a nanosensor for viral RNAs. EMBO Rep 13, 7-8.

Jiang, X., and Chen, Z.J. (2011). Viperin links lipid bodies to immune defense. Immunity 34, 285-287.

Liu, S., and Chen, Z.J. (2011). Expanding role of ubiquitination in NF-kappaB signaling. Cell Res 21, 6-21.

Sun, L., Liu, S., and Chen, Z.J. (2010) SnapShot: Pathways of Antiviral innate immunity. Cell 140, 436.

Skaug, B., and Chen, Z.J. (2010) Emerging role of ISG15 in antiviral immunity. Cell 143, 187-190.

Bhoj, V.G., and Chen, Z. J. (2009) Ubiquitylation in innate and adaptive immunity. Nature 458, 430-437.

Skaug B., Jiang, X., and Chen,Z. J. (2009) The role of ubiquitin in NF-kB Regulatory Pathways. Annu. Rev. Biochem. 78, 769-796.

Adhikari, A., and Chen, Z.J. (2009) Diversity of polyubiquitin chains. Developmental Cell 16, 485-486.

Chen, Z.J., and Sun, L.J. (2009). Nonproteolytic functions of ubiquitin in cell signaling. Molecular Cell 33, 275-286.

Chiu, Y.H., Zhao, M., and Chen, Z.J. (2009) Ubiquitin in NF-kB Signaling. Chemical Review 109, 1549-1560.

Zeng, W., and Chen, Z.J. (2008) MITAgating viral infection. Immunity 29, 513-515.

Bhoj, V.G., and Chen, Z. J. (2008) Linking retroelements to autoimmunity. Cell 134, 569-571.

Bhoj, V.G., and Chen, Z. J. (2008) Mitochondrial antiviral signaling. In Cellular Signaling and Innate Immune Responses to RNA Virus Infections. A. Brasier, A. Garcia-Sastre, S.M. Lemon, eds. (Washington D.C: ASM Press). pp 39-51.

Seth, R. B., and Chen, Z. J. (2007). Smads keep TABs on inflammation. Nat Immunol 8, 477-478.

Adhikari, A., Xu, M., and Chen, Z. J. (2007). Ubiquitin-mediated activation of TAK1 and IKK. Oncogene 26, 3214-3226.

Fitzgerald K.A., and Chen, Z.J. (2006) Sorting out Toll signals. Cell 125, 834-836.

Seth, R. B., Sun, L., and Chen, Z. J. (2006). Antiviral innate immunity pathways. Cell Res 16, 141-147.

Chen, Z. J., Bhoj, V., and Seth, R. B. (2006). Ubiquitin, TAK1 and IKK: is there a connection? Cell Death Differ. 1-6.

Schulman, B. A., and Chen, Z. J. (2005). Protein ubiquitination: CHIPping away the symmetry. Molecular Cell 20, 653-655.

Chen, Z.J. (2005) Ubiquitin signaling in the NF-kB pathway. Nature Cell Biology 7, 758-765.

van Oers, N. S., and Chen, Z. J. (2005). Kinasing and clipping down the NF-kB trail. Science 308, 65-66.

Xia, Z. P., and Chen, Z. J. (2005). TRAF2: a double-edged sword? Sci STKE 2005, pe7.

Pineda, G., Ea, C-K., and Chen, Z.J. (2005) Ubiquitination and TRAF signaling. In TRAFs. H, Wu, eds. Landes Bioscience.

Sun, L., and Chen, Z.J. (2004). The novel functions of ubiquitination in signaling. Curr Opin Cell Biol 16, 119-126.

Chen, Z.J. and Fuchs, S. Y. (2004). Ubiquitin-dependent activation of NF-kB: K63-linked ubiquitin chains – a link to cancer? Cancer Biol Ther 3, 286-288.

Deng, L., and Chen, Z.J. (2003) Role of ubiquitin in NF-kB signaling. In Nuclear Factor kB. Regulation and Role in Disease. R. Beyaert, eds. (Kluwer). pp 139-160.

Collaborative papers

Peisley A, Wu B, Xu H, Chen ZJ, Hur S. (2014) Structural basis for ubiquitin-mediated antiviral signal activation by RIG-I. Nature. 2014 Mar 2. Epub ahead of print

Yoo SH, Mohawk JA, Siepka SM, Shan Y, Huh SK, Hong HK, Kornblum I, Kumar V, Koike N, Xu M, Nussbaum J, Liu X, Chen Z, Chen ZJ, Green CB, Takahashi JS. (2013) Competing E3 ubiquitin ligases govern circadian periodicity by degradation of CRY in nucleus and cytoplasm. Cell. 152(5):1091-105.

Hao YH, Doyle JM, Ramanathan S, Gomez TS, Jia D, Xu M, Chen ZJ, Billadeau DD, Rosen MK, Potts PR. (2013) Regulation of WASH-dependent actin polymerization and protein trafficking by ubiquitination. Cell. 152(5):1051-64.

Yin, Q., Tian, Y., Kabaleeswaran, V., Jiang, X., Tu, D., Eck., M.J., Chen, Z.J., and Wu, H. (2012) Cyclic di-GMP sensing via the innate immune signaling protein STING. Molecular Cell 46, 735-745.

Xu, K., Sacharidou, A., Fu, S., Chong, D.C., Skaug, B., Chen, Z.J., Davis, G.E., and Cleaver, O. (2011). Blood vessel tubulogenesis requires Rasip1 regulation of GTPase signaling. Dev Cell 20, 526-539.

Dixit, E., Boulant, S., Zhang, Y., Lee, A.S., Odendall, C., Shum, B., Hacohen, N., Chen, Z.J., Whelan, S.P., Fransen, M., Nibert, M. L., Superti-Furga, G., Kagan, J.C. (2010) Peroxisomes are signaling platforms for antiviral innate immunity. Cell 141, 668-681.

Dong, X., Feng, H., Sun, Q., Li, H., Wu, T.T., Sun, R., Tibbetts, S.A., Chen, Z.J., and Feng, P. (2010) Murine gamma-herpesvirus 68 hijacks MAVS and IKKbeta to initiate lytic replication. PLoS Pathog 6, e1001001.

Huang, H.R., Chen, Z.J., Kunes, S., Chang, G.D., and Maniatis, T. (2010) Endocytic pathway is required for Drosophila Toll innate immune signaling. Proc Natl Acad Sci USA 107, 8322-8327.

McWhirter, S.M., Barbalat, R., Monroe, K.M., Fontana, M.F., Hyodo, M., Joncker, N.T., Ishii, K.J., Akira, S., Colonna, M., Chen, Z.J., Fitzgerald K.A., Hayakawa Y., and Vance R.E. (2009). A host type I interferon response is induced by cytosolic sensing of the bacterial second messenger cyclic-di-GMP. J Exp Med. 206, 1899-1911.

Liu, C., Qian, W., Qian, Y., Giltiay, N.V., Lu, Y., Swaidani, S., Misra, S., Deng, L., Chen, Z.J., and Li, X. (2009). Act1, a U-box E3 ubiquitin ligase for IL-17 signaling. Sci Signal 2, ra63.

Rasmussen, S.B., Jensen, S.B., Nielsen, C., Quartin, E., Kato, H., Chen, Z.J., Silverman, R.H., Akira, S., and Paludan, S.R. (2009). Herpes simplex virus infection is sensed by both Toll-like receptors and retinoic acid-inducible gene-like receptors, which synergize to induce type I interferon production. J Gen Virol 90, 74-78.

Lei, Y., Moore, C.B., Liesman, R.M., O'Connor, B.P., Bergstralh, D.T., Chen, Z.J., Pickles, R.J., and Ting, J.P. (2009). MAVS-mediated apoptosis and its inhibition by viral proteins. PLoS ONE 4, e5466.

Moore, C.B. Bergstralh, D.T., Duncan, J.A. Lei, Y., Morrison, T.E., Accavitti-Loper, M.A., Madden, V.J., Sun, L., Lich, J.D., Heise, M.T., Chen, Z.J., and Ting., J. P-Y. (2008) NLRX1 is a regulator of mitochondrial antiviral immunity. Nature 451, 573-577.

Kang, M. J., Lee, C. G., Lee, J. Y., Dela Cruz, C. S., Chen, Z. J., Enelow, R., and Elias, J. A. (2008). Cigarette smoke selectively enhances viral PAMP- and virus-induced pulmonary innate immune and remodeling responses in mice. J Clin Invest 118, 2771-2784.

Coornaert, B., Baens, M., Heyninck, K., Bekaert, T., Haegman, M., Staal, J., Sun, L., Chen, Z. J., Marynen, P., and Beyaert, R. (2008). T cell antigen receptor stimulation induces MALT1 paracaspase-mediated cleavage of the NF-kappaB inhibitor A20. Nat Immunol 9, 263-271.

Deng, L., Dai, P., Parikh, T., Cao, H., Bhoj, V., Sun, Q., Chen, Z., Merghoub, T., Houghton, A., and Shuman, S. (2008). Vaccinia virus subverts a MAVS-dependent innate immune response in keratinocytes through its dsRNA binding protein E3. J Virol. 82, 10735.

Xiao, H., Qian, W., Staschke, K., Jiang, Z., Qian, Y., Cui, G., Deng, L., Chen, Z. J., Gilmour, R., and Li, X. (2008). Pellino 3b negatively regulates IL-1-induced TAK1-dependent NFkappa B activation. J Biol Chem 283, 14654-14664.

Gack, M. U., Shin, Y. C., Joo, C. H., Urano, T., Liang, C., Sun, L., Takeuchi, O., Akira, S., Chen, Z.J.., Inoue, S., and Jung, J. U. (2007). TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity. Nature 446, 916-920.

Rasmussen, S. B., Sorensen, L. N., Malmgaard, L., Ank, N., Baines, J. D., Chen, Z. J., and Paludan, S. R. (2007). Type I interferon production during herpes simplex virus infection is controlled by cell-type-specific viral recognition through Toll-like receptor 9, the mitochondrial antiviral signaling protein pathway, and novel recognition systems. J Virol 81, 13315-13324.

Zhou, R., Silverman, N., Hong, M., Liao, D. S., Chung, Y., Chen, Z. J., and Maniatis, T. (2005). The role of ubiquitination in Drosophila innate immunity. J Biol Chem 280, 34048-34055.

Wan, J., Sun, L., Mendoza, J. W., Chui, Y. L., Huang, D. P., Chen, Z. J., Suzuki, N., Suzuki, S., Yeh, W. C., Akira, S., et al. (2004). Elucidation of the c-Jun N-terminal kinase pathway mediated by Epstein-Barr virus-encoded latent membrane protein 1. Mol Cell Biol 24, 192-199.

Misra, A., Haudek, S. B., Knuefermann, P., Vallejo, J. G., Chen, Z. J., Michael, L. H., Sivasubramanian, N., Olson, E. N., Entman, M. L., and Mann, D. L. (2003). Nuclear factor-kappaB protects the adult cardiac myocyte against ischemia-induced apoptosis in a murine model of acute myocardial infarction. Circulation 108, 3075-3078.

Davies, B.A., Topp, J.D., Sfeir, A.J., Katzmann, D. J., Carney, D.S., Tall, G.G., Friedberg, A. S., Deng, L., Chen, Z.J., and Horazdovsky, B. F. (2003) Vps9p CUE domain ubiquitin binding is required for efficient endocytic protein traffic. J. Biol. Chem. 278, 19826-19833.

Heussler, V.T., Rottenberg, S, Schwab, R, Küenzi,P. Fernandez, P.C., McKellar, S., Shiels, B, Chen, Z.J., Orth, K., Wallach, D., Dobbelaere, D.A.E. (2002) Hijacking of host cell IKK signalosomes by the transforming parasite Theileria. Science 298, 1033-1036.

Fredericksen, B., Akkaraju, G.R., Foy, E., Wang, C., Pflugheber, J., Chen, Z.J., Gale, M. Jr. (2002) Activation of the interferon-beta promoter during hepatitis C virus RNA replication. Viral Immunol 15, 29-40.

Yang, J., Lin, Y., Guo, Z., Cheng, J., Huang, J., Deng, L., Liao, W., Chen, Z.J., Liu, Z-g., and Su, B. (2001) The essential role of MEKK3 in TNF-induced NF-kB activation. Nature Immunology 2, 620-624.

Lee, F. Peters, R. Chen, Z.J., and Maniatis, T. (2001) Activation of nuclear factor-kappaB. In Leukocyte Recruitment, Endothelial Cell Adhesion Molecules, and Transcriptional Control: Insights for Drug Discovery. T. Collins, eds (Kluwer Academic Publishers).

Haudek, S. B., Spencer, E., Bryant, D.D., White, J.D., Maass, D., Horton, J.W., Chen, Z.J., and Giroir, B. (2001) Overexpression of cardiac IkBa prevents endotoxin-induced myocardial dysfunction. Am J Physiol Heart Circ Physiol. 280, H962-968.

Li., K., Li, Y., Shelton, J.M., Richardson, J.A., Spencer, E., Chen, Z.J., Wang., X., and Williams,R.S. (2000) Cytochrome C deficiency causes embryonic lethality and attenuates stress-induced apoptosis. Cell 101, 389-399.