Tbk1

Summary

Gene Symbol: Tbk1
Description: TANK-binding kinase 1
Alias: 1200008B05Rik, AI462036, AW048562, serine/threonine-protein kinase TBK1, T2K
Species: mouse

Top Publications

  1. pmc Deficiency of T2K leads to apoptotic liver degeneration and impaired NF-kappaB-dependent gene transcription
    M Bonnard
    Amgen Institute, Ontario Cancer Institute and the Department of Medical Biophysics, University of Toronto, 620 University Avenue, Toronto, Ontario, Canada
    EMBO J 19:4976-85. 2000
  2. pmc A distinct role of Riplet-mediated K63-Linked polyubiquitination of the RIG-I repressor domain in human antiviral innate immune responses
    Hiroyuki Oshiumi
    Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Kita ku, Sapporo, Japan
    PLoS Pathog 9:e1003533. 2013
  3. pmc NEMO binds ubiquitinated TANK-binding kinase 1 (TBK1) to regulate innate immune responses to RNA viruses
    Lingyan Wang
    Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS ONE 7:e43756. 2012
  4. pmc The kinase TBK1 controls IgA class switching by negatively regulating noncanonical NF-κB signaling
    Jin Jin
    Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
    Nat Immunol 13:1101-9. 2012
  5. pmc Inhibition of TANK binding kinase 1 by herpes simplex virus 1 facilitates productive infection
    Yijie Ma
    Department of Microbiology and Immunology, College of Medicine, University of Illinois, Chicago, Illinois, USA
    J Virol 86:2188-96. 2012
  6. pmc Functional dissection of the TBK1 molecular network
    Adriana Goncalves
    CeMM Research Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria
    PLoS ONE 6:e23971. 2011
  7. pmc IkappaB kinase epsilon and TANK-binding kinase 1 activate AKT by direct phosphorylation
    Xiaoduo Xie
    Department of Pharmacology and Moores Cancer Center, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 108:6474-9. 2011
  8. pmc TBK1 directly engages Akt/PKB survival signaling to support oncogenic transformation
    Yi Hung Ou
    Department of Cell Biology, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
    Mol Cell 41:458-70. 2011
  9. doi Akt contributes to activation of the TRIF-dependent signaling pathways of TLRs by interacting with TANK-binding kinase 1
    Sun Myung Joung
    School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea
    J Immunol 186:499-507. 2011
  10. pmc IFI16 is an innate immune sensor for intracellular DNA
    Leonie Unterholzner
    School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland
    Nat Immunol 11:997-1004. 2010

Scientific Experts

  • Hiroyuki Oshiumi
  • Ken J Ishii
  • Kouhei Yamashita
  • Ahmet Civas
  • Shizuo Akira
  • Katherine A Fitzgerald
  • Genhong Cheng
  • Glen N Barber
  • Taro Kawai
  • Andrea L Radtke
  • Zhaozhao Jiang
  • Osamu Takeuchi
  • Eddy T H Goh
  • Philip Cohen
  • Yijie Ma
  • Hiroki Kato
  • Shruti Sharma
  • Hong Tang
  • Adriana Goncalves
  • Nadege Goutagny
  • Andrea K Miyahira
  • Zachary J Roberts
  • Masahiro Yamamoto
  • Yujie Ren
  • Beichu Guo
  • Fuan Wang
  • Sayaka Tsuzuki
  • Zexing Li
  • Swarupa Panda
  • Maroof Hasan
  • Hong Bing Shu
  • Quanhong Sun
  • Eric Lam
  • Bart Everts
  • Hye Ri Kang
  • Susana Soo Yeon Kim
  • Chikako Ono
  • Lu Zhang
  • Kosuke Matsui
  • Kouji Kobiyama
  • Daniela Bruni
  • Ying Cing Lin
  • Neha Kamran
  • Chang Shu
  • Shintaro Sato
  • Shigeki Chiba
  • Manohar Pilli
  • Lingyan Wang
  • Matthias Farlik
  • Mireille Delhase
  • Takayuki Abe
  • Tatsuya Saitoh
  • Jin Jin
  • Meng Zhang
  • Yoshiharu Matsuura
  • Swamy Kumar Polumuri
  • Fangfang Qu
  • Yi Ping Liu
  • Peter C F Cheung
  • Andrea K Perry
  • J Simon C Arthur
  • Delia Gutman
  • Qi Da
  • Yi Hung Ou
  • Xiaoduo Xie
  • Huihui Chen
  • Catherine E Gleason
  • Hilary Smith
  • Michael Gale
  • Sun Myung Joung
  • Thomas Marichal
  • Robert Gourlay
  • Xingguang Liu
  • Philipp Wild
  • Zhipeng Yan
  • Bin He
  • J Perry Hall
  • Joan Ní Gabhann
  • Tomohiro Watanabe
  • Tetsuo Tsuchida
  • Kislay Parvatiyar
  • Mikyoung Chang
  • Erica Marchlik
  • Thomas Decker
  • Leonie Unterholzner
  • Shao Cong Sun
  • Xuetao Cao
  • Giulio Superti-Furga
  • Keiryn L Bennett
  • Stefanie N Vogel

Detail Information

Publications78

  1. pmc Deficiency of T2K leads to apoptotic liver degeneration and impaired NF-kappaB-dependent gene transcription
    M Bonnard
    Amgen Institute, Ontario Cancer Institute and the Department of Medical Biophysics, University of Toronto, 620 University Avenue, Toronto, Ontario, Canada
    EMBO J 19:4976-85. 2000
    ..In this study, we purified and characterized a novel kinase (T2K, also known as TBK1 or NAK), which associates with TRAF2 and exhibits kinase activity towards I-kappaBalpha in vitro...
  2. pmc A distinct role of Riplet-mediated K63-Linked polyubiquitination of the RIG-I repressor domain in human antiviral innate immune responses
    Hiroyuki Oshiumi
    Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Kita ku, Sapporo, Japan
    PLoS Pathog 9:e1003533. 2013
    ..autorepression of its N-terminal CARDs, which leads to the association of RIG-I with TRIM25 ubiquitin ligase and TBK1 protein kinase. Our data indicate that Riplet is a prerequisite for TRIM25 to activate RIG-I signaling...
  3. pmc NEMO binds ubiquitinated TANK-binding kinase 1 (TBK1) to regulate innate immune responses to RNA viruses
    Lingyan Wang
    Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS ONE 7:e43756. 2012
    ..b>TBK1 is a critical kinase implicated in RLR-dependent IFN transcription...
  4. pmc The kinase TBK1 controls IgA class switching by negatively regulating noncanonical NF-κB signaling
    Jin Jin
    Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
    Nat Immunol 13:1101-9. 2012
    ..Here we identify the kinase TBK1 as a pivotal negative regulator of class switching to the immunoglobulin A (IgA) isotype...
  5. pmc Inhibition of TANK binding kinase 1 by herpes simplex virus 1 facilitates productive infection
    Yijie Ma
    Department of Microbiology and Immunology, College of Medicine, University of Illinois, Chicago, Illinois, USA
    J Virol 86:2188-96. 2012
    ..Here we report that γ(1)34.5 inhibits TANK binding kinase 1 (TBK1) through its amino-terminal sequences, which facilitates viral replication and neuroinvasion...
  6. pmc Functional dissection of the TBK1 molecular network
    Adriana Goncalves
    CeMM Research Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria
    PLoS ONE 6:e23971. 2011
    TANK-binding kinase 1 (TBK1) and inducible IκB-kinase (IKK-i) are central regulators of type-I interferon induction...
  7. pmc IkappaB kinase epsilon and TANK-binding kinase 1 activate AKT by direct phosphorylation
    Xiaoduo Xie
    Department of Pharmacology and Moores Cancer Center, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 108:6474-9. 2011
    ..Here we show that the atypical IκB kinase ε and TANK-binding kinase 1 (IKKε/TBK1) phosphorylate AKT on both the hydrophobic motif and the activation loop in a manner dependent on PI3K signaling...
  8. pmc TBK1 directly engages Akt/PKB survival signaling to support oncogenic transformation
    Yi Hung Ou
    Department of Cell Biology, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
    Mol Cell 41:458-70. 2011
    The innate immune-signaling kinase, TBK1, couples pathogen surveillance to induction of host defense mechanisms. Pathological activation of TBK1 in cancer can overcome programmed cell death cues, enabling cells to survive oncogenic stress...
  9. doi Akt contributes to activation of the TRIF-dependent signaling pathways of TLRs by interacting with TANK-binding kinase 1
    Sun Myung Joung
    School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea
    J Immunol 186:499-507. 2011
    ..We show that Akt is a downstream molecule of TRIF/TANK-binding kinase 1 (TBK1) and plays an important role in the activation of IRF3 by TLR3 and -4 agonists...
  10. pmc IFI16 is an innate immune sensor for intracellular DNA
    Leonie Unterholzner
    School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland
    Nat Immunol 11:997-1004. 2010
    ..IFI16 (p204) is the first PYHIN protein to our knowledge shown to be involved in IFN-β induction. Thus, the PYHIN proteins IFI16 and AIM2 form a new family of innate DNA sensors we call 'AIM2-like receptors' (ALRs)...
  11. pmc TAX1BP1 and A20 inhibit antiviral signaling by targeting TBK1-IKKi kinases
    Kislay Parvatiyar
    Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, University of Miami, Miller School of Medicine, Miami, Florida 33136, USA
    J Biol Chem 285:14999-5009. 2010
    ..Activation of IRF3 requires C-terminal phosphorylation by the upstream kinases TBK1-IKKi, where IRF3 phosphorylation promotes dimerization, and subsequent nuclear translocation to the IFNbeta ..
  12. pmc TANK-binding kinase-1 plays an important role during in vitro and in vivo type I IFN responses to DNA virus infections
    Andrea K Miyahira
    Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA
    J Immunol 182:2248-57. 2009
    TANK-binding kinase-1 (TBK1) and the inducible IkappaB kinase (IKK-i) have recently been shown to activate type I IFN responses elicited by intracellular detection of RNA or DNA from infecting viruses...
  13. pmc The DEAD-box helicase DDX3X is a critical component of the TANK-binding kinase 1-dependent innate immune response
    Didier Soulat
    Department of Infection Biology, Max F Perutz Laboratories, University of Vienna, Vienna, Austria
    EMBO J 27:2135-46. 2008
    TANK-binding kinase 1 (TBK1) is of central importance for the induction of type-I interferon (IFN) in response to pathogens. We identified the DEAD-box helicase DDX3X as an interaction partner of TBK1...
  14. pmc Regulation of IkappaB kinase-related kinases and antiviral responses by tumor suppressor CYLD
    Minying Zhang
    Department of Immunology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    J Biol Chem 283:18621-6. 2008
    The IkappaB kinase (IKK)-related kinases, IKKepsilon and TBK1, participate in the induction of type I interferons (IFNs) during viral infections...
  15. doi TANK-binding kinase-1 delineates innate and adaptive immune responses to DNA vaccines
    Ken J Ishii
    Exploratory Research for Advanced Technology ERATO, Japan Science and Technology Agency JST
    Nature 451:725-9. 2008
    ..Here we demonstrate in vivo that TANK-binding kinase 1 (TBK1), a non-canonical IkappaB kinase, mediates the adjuvant effect of DNA vaccines and is essential for its ..
  16. pmc Involvement of the ubiquitin-like domain of TBK1/IKK-i kinases in regulation of IFN-inducible genes
    Fumiyo Ikeda
    Institute of Biochemistry II, Goethe University Medical School, Frankfurt, Germany
    EMBO J 26:3451-62. 2007
    TANK-binding kinase 1 (TBK1/NAK/T2K) and I-kappaB Kinase (IKK-i/IKK-epsilon) play important roles in the regulation of interferon (IFN)-inducible genes during the immune response to bacterial and viral infections...
  17. ncbi Immune activation of type I IFNs by Listeria monocytogenes occurs independently of TLR4, TLR2, and receptor interacting protein 2 but involves TNFR-associated NF kappa B kinase-binding kinase 1
    Ryan M O'Connell
    Department of Microbiology, Immunology and Molecular Genetics, University of California, CA 90095, USA
    J Immunol 174:1602-7. 2005
    ..pathway involving the serine-threonine kinase TNFR-associated NF-kappaB kinase (TANK)-binding kinase 1 (TBK1)...
  18. pmc NF-kappaB activation by a signaling complex containing TRAF2, TANK and TBK1, a novel IKK-related kinase
    J L Pomerantz
    Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
    EMBO J 18:6694-704. 1999
    ..In this report, we investigate the mechanism of the stimulatory activity of TANK. We find that TANK interacts with TBK1 (TANK-binding kinase 1), a novel IKK-related kinase that can activate NF-kappaB in a kinase-dependent manner...
  19. pmc IFN-regulatory factor 3-dependent gene expression is defective in Tbk1-deficient mouse embryonic fibroblasts
    Sarah M McWhirter
    Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA
    Proc Natl Acad Sci U S A 101:233-8. 2004
    ..IKK)-related kinases, IKK-epsilon and Traf family member-associated NF-kappaB activator (TANK)-binding kinase 1 (TBK1), in the phosphorylation of IRF3...
  20. ncbi RalB GTPase-mediated activation of the IkappaB family kinase TBK1 couples innate immune signaling to tumor cell survival
    Yuchen Chien
    Department of Cell Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA
    Cell 127:157-70. 2006
    ..find that the RalB/Sec5 effector complex directly recruits and activates the atypical IkappaB kinase family member TBK1. In cancer cells, constitutive engagement of this pathway, via chronic RalB activation, restricts initiation of ..
  21. pmc The roles of two IkappaB kinase-related kinases in lipopolysaccharide and double stranded RNA signaling and viral infection
    Hiroaki Hemmi
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    J Exp Med 199:1641-50. 2004
    ..Recently, two IkappaB kinase (IKK)-related kinases, inducible IkappaB kinase (IKK-i) and TANK-binding kinase 1 (TBK1), were suggested to act as IRF-3 kinases and be involved in IFN-beta production in Toll-like receptor (TLR) ..
  22. ncbi A Toll-like receptor-independent antiviral response induced by double-stranded B-form DNA
    Ken J Ishii
    Exploratory Research for Advanced Technology, Japan Science and Technology Agency, Research Institute for Microbial Diseases, Osaka University, Osaka 565 0871, Japan
    Nat Immunol 7:40-8. 2006
    ..IRF3 and the promoter of the gene encoding interferon-beta through a signaling pathway that required the kinases TBK1 and IKKi, whereas there was substantial activation of transcription factor NF-kappaB independent of both TBK and ..
  23. ncbi Cell type-specific involvement of RIG-I in antiviral response
    Hiroki Kato
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka 565 0871, Japan
    Immunity 23:19-28. 2005
    ..In contrast, plasmacytoid DCs, which produce large amounts of IFN-alpha, use the TLR system rather than RIG-I for viral detection. Taken together, RIG-I and the TLR system exert antiviral responses in a cell type-specific manner...
  24. ncbi Cutting edge: Role of TANK-binding kinase 1 and inducible IkappaB kinase in IFN responses against viruses in innate immune cells
    Kosuke Matsui
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan
    J Immunol 177:5785-9. 2006
    TANK-binding kinase 1 (TBK1) and inducible IkappaB kinase (IKK-i) are involved in the activation of transcription factors inducing the production of type I IFNs...
  25. pmc Differential requirement for TANK-binding kinase-1 in type I interferon responses to toll-like receptor activation and viral infection
    Andrea K Perry
    Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, 8 240 Factor Bldg, 10833 Le Conte Ave, Los Angeles, CA 90095, USA
    J Exp Med 199:1651-8. 2004
    TANK-binding kinase-1 (TBK1) and the inducible IkappaB kinase (IKK-i) have been shown recently to activate interferon (IFN) regulatory factor-3 (IRF3), the primary transcription factor regulating induction of type I IFNs...
  26. ncbi Modulation of the interferon antiviral response by the TBK1/IKKi adaptor protein TANK
    Beichu Guo
    Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California 90095, USA
    J Biol Chem 282:11817-26. 2007
    ..Thus, TANK may be a critical adaptor that regulates the assembly of the TANK-binding kinase 1-inducible IkappaB kinase complex with upstream signaling molecules in multiple antiviral pathways...
  27. ncbi The NEMO adaptor bridges the nuclear factor-kappaB and interferon regulatory factor signaling pathways
    Tiejun Zhao
    Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, McGill University, Montreal H3T 1E2, Canada
    Nat Immunol 8:592-600. 2007
    ..activation of IRF3 and IRF7 depended on the NF-kappaB modulator NEMO, which acted 'upstream' of the kinases TBK1 and IKKepsilon...
  28. pmc TBK1 protects vacuolar integrity during intracellular bacterial infection
    Andrea L Radtke
    Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America
    PLoS Pathog 3:e29. 2007
    TANK-binding kinase-1 (TBK1) is an integral component of Type I interferon induction by microbial infection...
  29. doi The E3 ubiquitin ligase Nrdp1 'preferentially' promotes TLR-mediated production of type I interferon
    Chen Wang
    National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai, China
    Nat Immunol 10:744-52. 2009
    ..MyD88-dependent activation of transcription factors NF-kappaB and AP-1 while promoting activation of the kinase TBK1 and transcription factor IRF3...
  30. pmc Phosphorylation of the autophagy receptor optineurin restricts Salmonella growth
    Philipp Wild
    Frankfurt Institute for Molecular Life Sciences and Institute of Biochemistry II, Goethe University School of Medicine, Frankfurt Main, Germany
    Science 333:228-33. 2011
    ..The protein kinase TANK binding kinase 1 (TBK1) phosphorylated optineurin on serine-177, enhancing LC3 binding affinity and autophagic clearance of cytosolic ..
  31. pmc TBK1 mediates critical effects of measles virus nucleocapsid protein (MVNP) on pagetic osteoclast formation
    Quanhong Sun
    Department of Medicine Hematology Oncology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
    J Bone Miner Res 29:90-102. 2014
    ..TANK-binding kinase 1 (TBK1) and IκB kinase-ϵ (IKKϵ) are IKK family members that complex with MVNP and activate both IRF3 and NF-κB ..
  32. pmc NLRC3, a member of the NLR family of proteins, is a negative regulator of innate immune signaling induced by the DNA sensor STING
    Lu Zhang
    Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA Department of Oral Biology, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Immunity 40:329-41. 2014
    ..is an intracellular DNA sensor that induces type I interferon through its interaction with TANK-binding kinase 1 (TBK1)...
  33. doi The tyrosine kinase Syk differentially regulates Toll-like receptor signaling downstream of the adaptor molecules TRAF6 and TRAF3
    Ying Cing Lin
    Department of Pharmacology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan
    Sci Signal 6:ra71. 2013
    ..stimulates the production of type I interferons (IFNs) through a pathway that depends on TRAF3 and the kinase TBK1 (TANK-binding kinase-1)...
  34. pmc Adenovirus detection by the cGAS/STING/TBK1 DNA sensing cascade
    Eric Lam
    Weill Medical College of Cornell University, Department of Microbiology and Immunology, Molecular Biology Graduate Program, New York, New York, USA
    J Virol 88:974-81. 2014
    ..Short hairpin RNA (shRNA) lentiviral vectors targeting TBK1, STING, and cGAS were established in murine MS1 endothelial and RAW 264.7 macrophage cell lines...
  35. pmc Innate immune response induced by baculovirus attenuates transgene expression in mammalian cells
    Chikako Ono
    Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
    J Virol 88:2157-67. 2014
    ..baculovirus was achieved in MEFs deficient for stimulator of interferon genes (STING), TANK binding kinase 1 (TBK1), IFN regulatory factor 3 (IRF3), or IFN-β promoter stimulator 1 (IPS-1), but not in those deficient for IRF7, ..
  36. pmc TLR-driven early glycolytic reprogramming via the kinases TBK1-IKKɛ supports the anabolic demands of dendritic cell activation
    Bart Everts
    Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri, USA
    Nat Immunol 15:323-32. 2014
    ..Signaling via the kinases TBK1, IKKɛ and Akt was essential for the TLR-induced increase in glycolysis by promoting the association of the ..
  37. pmc Murine gammaherpesvirus 68 encoding open reading frame 11 targets TANK binding kinase 1 to negatively regulate the host type I interferon response
    Hye Ri Kang
    Virus Host Interactions Laboratory, Department of Biosystems and Biotechnology, Division of Biotechnology, College of Life Sciences and Biotechnology, South Korea University, Seoul, Republic of Korea
    J Virol 88:6832-46. 2014
    ..MHV-68 ORF11 decreased IFN-β promoter activation by various factors, the signaling of which converges on TBK1-IRF3 activation. MHV-68 ORF11 directly interacted with both overexpressed and endogenous TBK1 but not with IRF3...
  38. doi DOK3 is required for IFN-β production by enabling TRAF3/TBK1 complex formation and IRF3 activation
    Susana Soo Yeon Kim
    Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228 Bioprocessing Technology Institute, Agency for Science, Technology and Research, Singapore 138668 and
    J Immunol 193:840-8. 2014
    ..DOK3 was shown to bind TBK1 and was required for its activation...
  39. pmc PPM1A regulates antiviral signaling by antagonizing TBK1-mediated STING phosphorylation and aggregation
    Zexing Li
    State Key Laboratory of Biomembrane and Membrane Biotechnology, Chinese Academy of Sciences, Chaoyang District, Beijing, China
    PLoS Pathog 11:e1004783. 2015
    ..its phosphatase activity-dependent manner, and in a line with this, PPM1A catalytically dephosphorylates STING and TBK1 in vitro...
  40. pmc Cytosolic Nuclease TREX1 Regulates Oligosaccharyltransferase Activity Independent of Nuclease Activity to Suppress Immune Activation
    Maroof Hasan
    Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Immunity 43:463-74. 2015
    ..This function of the TREX1 C terminus suggests a potential therapeutic option for TREX1-fs mutant-associated diseases. ..
  41. doi Deubiquitinase MYSM1 Regulates Innate Immunity through Inactivation of TRAF3 and TRAF6 Complexes
    Swarupa Panda
    Laboratory for Molecular Infection Medicine Sweden MIMS, Umea University, 90 187, Umea, Sweden Department of Molecular Biology, Umea University, 90 187, Umea, Sweden Umeå Centre for Microbial Research UCMR, Umea University, 90 187, Umea, Sweden
    Immunity 43:647-59. 2015
    ..This study identifies MYSM1 as a key negative regulator of the innate immune system that guards against an overzealous self-destructive immune response. ..
  42. doi TANK-binding kinase 1-dependent or -independent signaling elicits the cell-type-specific innate immune responses induced by the adenovirus vector
    Sayaka Tsuzuki
    Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565 0871, Japan
    Int Immunol 28:105-15. 2016
    ..the impacts of viral nucleic acids on innate immune responses in vivo, we administered transgene-expressing Adv to Tbk1-deficient mice...
  43. pmc S6K-STING interaction regulates cytosolic DNA-mediated activation of the transcription factor IRF3
    Fuan Wang
    McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada
    Nat Immunol 17:514-22. 2016
    ..the kinase domain, but not the kinase function, of S6K1 was required for the S6K1-STING interaction and that the TBK1 critically promoted this process...
  44. pmc The Type I Interferon-IRF7 Axis Mediates Transcriptional Expression of Usp25 Gene
    Yujie Ren
    From the State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China
    J Biol Chem 291:13206-15. 2016
    ..Our study has uncovered a previously unknown mechanism by which viral infection or LPS induces up-regulation of USP25...
  45. doi Activation of STAT6 by STING is critical for antiviral innate immunity
    Huihui Chen
    State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China
    Cell 147:436-46. 2011
    ..named MITA/ERIS) to recruit STAT6 to the endoplasmic reticulum, leading to STAT6 phosphorylation on Ser(407) by TBK1 and Tyr(641), independent of JAKs...
  46. pmc TRAF-interacting protein (TRIP) negatively regulates IFN-β production and antiviral response by promoting proteasomal degradation of TANK-binding kinase 1
    Meng Zhang
    Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Immunology, Shandong University School of Medicine, Shandong 250012, China
    J Exp Med 209:1703-11. 2012
    TANK-binding kinase 1 (TBK1) plays an essential role in Toll-like receptor (TLR)- and retinoic acid-inducible gene I (RIG-I)-mediated induction of type I interferon (IFN; IFN-α/β) and host antiviral responses...
  47. pmc TANK-binding kinase 1 (TBK1) controls cell survival through PAI-2/serpinB2 and transglutaminase 2
    Mireille Delhase
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 109:E177-86. 2012
    ..Genetic studies in mice have identified the IκB kinase-related kinase TANK-binding kinase 1 (TBK1; also called NAK or T2K) as an additional regulatory molecule that promotes survival downstream of TNF, but the ..
  48. doi Identification of the protein kinases that activate the E3 ubiquitin ligase Pellino 1 in the innate immune system
    Eddy T H Goh
    MRC Protein Phosphorylation Unit and Scottish Institute for Cell Signalling, Sir James Black Centre, University of Dundee, Dundee DD1 5EH, Scotland, U K
    Biochem J 441:339-46. 2012
    ..IRAK1 and IRAK4, or the IKK {IκB [inhibitor of NF-κB (nuclear factor κB)] kinase}-related kinases [IKKϵ and TBK1 (TANK {TRAF [TNF (tumour-necrosis-factor)-receptor-associated factor]-associated NF-κB activator}-binding kinase 1)..
  49. pmc Structural insights into the functions of TBK1 in innate antimicrobial immunity
    Chang Shu
    Department of Biochemistry and Biophysics, Texas A and M University, College Station, TX 77843 2128, USA
    Structure 21:1137-48. 2013
    Tank-binding kinase 1 (TBK1) is a serine/threonine protein-kinase mediating innate antimicrobial immunity. TBK1 is involved in the signaling of TLRs, RLRs, and STING-mediated sensing of cytosolic DNA...
  50. doi A novel IRAK1-IKKε signaling axis limits the activation of TAK1-IKKβ downstream of TLR3
    Daniela Bruni
    Institute of Immunology, National University of Ireland Maynooth, Maynooth, County Kildare, Ireland
    J Immunol 190:2844-56. 2013
    ..Recently, IKKε and TANK-binding kinase 1 (TBK1) were reported to limit activation of the NF-κB pathway downstream of IL-1R, TNFR1, and TLRs...
  51. pmc Toll-like receptor ligands induce expression of the costimulatory molecule CD155 on antigen-presenting cells
    Neha Kamran
    Immunology Programme, Department of Microbiology, National University of Singapore, Singapore, Singapore
    PLoS ONE 8:e54406. 2013
    ..Our data suggest that CD155 regulates T(h)2 differentiation. Targeting of CD155 in immunization protocols using peptides may represent a promising new approach to boost protective humoral immunity in viral vaccines...
  52. pmc Endoplasmic reticulum stress regulates the innate immunity critical transcription factor IRF3
    Yi Ping Liu
    Department of Pediatrics, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53792, USA
    J Immunol 189:4630-9. 2012
    ..Our results also suggest certain types of ER stress accomplish IRF3 phosphorylation by co-opting existing innate immune pathogen response pathways. These data have implications for diseases involving ER stress and type I IFN...
  53. pmc TBK-1 promotes autophagy-mediated antimicrobial defense by controlling autophagosome maturation
    Manohar Pilli
    Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, NE, Albuquerque, NM 87131, USA
    Immunity 37:223-34. 2012
    ..Thus, TBK-1 is a key regulator of immunological autophagy and is responsible for the maturation of autophagosomes into lytic bactericidal organelles...
  54. pmc TRAF6-dependent Act1 phosphorylation by the IκB kinase-related kinases suppresses interleukin-17-induced NF-κB activation
    Fangfang Qu
    The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China
    Mol Cell Biol 32:3925-37. 2012
    ..Here we show that TANK binding kinase 1 (TBK1), the other IKK-related kinase, directly phosphorylated Act1 on three other Ser sites to suppress IL-17R-mediated ..
  55. pmc Transcriptional regulation of murine IL-33 by TLR and non-TLR agonists
    Swamy Kumar Polumuri
    Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
    J Immunol 189:50-60. 2012
    ..Together, these studies greatly extend what is currently known about the regulation of IL-33 induction in macrophages stimulated by bacterial and viral agonists that engage distinct innate immune signaling pathways...
  56. pmc Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1
    Shigeki Chiba
    Research Center for Infection Associated Cancer, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan
    Nat Immunol 13:832-42. 2012
    ..Our findings define a mechanism whereby tumor microenvironments suppress antitumor immunity mediated by nucleic acids...
  57. pmc Contribution of a TANK-binding kinase 1-interferon (IFN) regulatory factor 7 pathway to IFN-γ-induced gene expression
    Matthias Farlik
    Max F Perutz Laboratories, Department of Genetics, Microbiology and Immunobiology, University of Vienna, Vienna, Austria
    Mol Cell Biol 32:1032-43. 2012
    ..control of the Gbp2 gene required the presence and basal activity of the S/T kinase TANK-binding kinase 1 (TBK1), whereas the binding of IRF7 to the Gbp2 promoter did not...
  58. pmc The chemotherapeutic agent DMXAA potently and specifically activates the TBK1-IRF-3 signaling axis
    Zachary J Roberts
    Department of Microbiology and Immunology, University of Maryland Baltimore, Baltimore, MD 21201, USA
    J Exp Med 204:1559-69. 2007
    ..Our data demonstrate that DMXAA is a novel and specific activator of the TANK-binding kinase 1 (TBK1)-interferon (IFN) regulatory factor 3 (IRF-3) signaling pathway...
  59. ncbi IRF3-dependent type I interferon response in B cells regulates CpG-mediated antibody production
    Gagik Oganesyan
    Department of Microbiology, Immunology and Molecular Genetics, University of California at Los Angeles, California 90095, USA
    J Biol Chem 283:802-8. 2008
    ..on the transcription factor IRF3, but similar to dendritic cells this pathway was independent of the IRF3 kinase TBK1. Utilizing type I IFN receptor-deficient mice, we were able to demonstrate that this IFN pathway enhanced Syndecan-..
  60. ncbi The Type I IFN response to infection with Mycobacterium tuberculosis requires ESX-1-mediated secretion and contributes to pathogenesis
    Sarah A Stanley
    Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94158, USA
    J Immunol 178:3143-52. 2007
    ..We propose that the ESX-1 secretion system secretes effectors into the cytosol of infected macrophages, thereby triggering the type I IFN response for the manipulation of host immunity...
  61. doi Homeostatic maintenance of pathogen-containing vacuoles requires TBK1-dependent regulation of aquaporin-1
    Andrea L Radtke
    Department of Microbiology and Immunology, University of Michigan Medical School, 1150 W Medical Center Drive, 5641 Medical Sciences II, Ann Arbor, MI 48109 5620, USA
    Cell Microbiol 10:2197-207. 2008
    ..TANK-binding-kinase-1 (TBK1), a kinase of the IkappaB kinase family, is required for maintaining integrity of pathogen-containing vacuoles (PCV)..
  62. doi Negative regulation of virus-triggered IFN-beta signaling pathway by alternative splicing of TBK1
    Weiwen Deng
    Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
    J Biol Chem 283:35590-7. 2008
    ..Induction of Type I IFNs is a central event in antiviral responses and must be tightly controlled. The protein kinase TBK1 is critically involved in virus-triggered type I IFN signaling...
  63. pmc Control of TANK-binding kinase 1-mediated signaling by the gamma(1)34.5 protein of herpes simplex virus 1
    Dustin Verpooten
    Department of Microbiology and Immunology, College of Medicine, University of Illinois, Chicago, Illinois 60612, USA
    J Biol Chem 284:1097-105. 2009
    TANK-binding kinase 1 (TBK1) is a key component of Toll-like receptor-dependent and -independent signaling pathways. In response to microbial components, TBK1 activates interferon regulatory factor 3 (IRF3) and cytokine expression...
  64. pmc A novel IFN regulatory factor 3-dependent pathway activated by trypanosomes triggers IFN-beta in macrophages and fibroblasts
    Anne Danielle C Chessler
    Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA
    J Immunol 181:7917-24. 2008
    ..In this study, we report that signaling through TBK1 and IFN regulatory factor 3 is required for T. cruzi-mediated expression of IFN-beta...
  65. doi TANK-binding kinase 1 mediates phosphorylation of insulin receptor at serine residue 994: a potential link between inflammation and insulin resistance
    Marina C Muñoz
    Instituto de Química y Fisicoquímica Biológicas UBA CONICET, IQUIFIB Cátedra de Farmacología, Facultad de Farmacia y Bioquimica, Universidad de Buenos Aires, Junin 956, Capital Federal, 1113 Buenos Aires, Argentina
    J Endocrinol 201:185-97. 2009
    ..In this study, we demonstrated that Ser994 of IR is a direct substrate for TANK-binding kinase 1 (TBK1), a new member of the IKK-related kinase family...
  66. doi Absence of SHIP-1 results in constitutive phosphorylation of tank-binding kinase 1 and enhanced TLR3-dependent IFN-beta production
    Joan Ní Gabhann
    Molecular and Cellular Therapeutics, Royal College of Surgeons, Ireland Research Institute, Dublin 2, Ireland
    J Immunol 184:2314-20. 2010
    ..Further dissection of the IFN-beta pathway implicates TANK-binding kinase 1 (TBK1) as the target for SHIP-1...
  67. ncbi Involvement of the IkappaB kinase (IKK)-related kinases tank-binding kinase 1/IKKi and cullin-based ubiquitin ligases in IFN regulatory factor-3 degradation
    Annie Bibeau-Poirier
    Faculty of Pharmacy, University of Montreal, Montreal, Canada
    J Immunol 177:5059-67. 2006
    ..In addition, no degradation of IRF-3 was observed in TBK1(-/-) mouse embryonic fibroblasts...
  68. pmc NOD1 contributes to mouse host defense against Helicobacter pylori via induction of type I IFN and activation of the ISGF3 signaling pathway
    Tomohiro Watanabe
    Mucosal Immunity Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892, USA
    J Clin Invest 120:1645-62. 2010
    ..This in turn led to activation of TANK-binding kinase 1 (TBK1) and IkappaB kinase epsilon (IKKepsilon) and the subsequent activation of IFN regulatory factor 7 (IRF7)...
  69. doi Mice lacking Tbk1 activity exhibit immune cell infiltrates in multiple tissues and increased susceptibility to LPS-induced lethality
    Erica Marchlik
    Department of Inflammation, Wyeth Research, Cambridge, MA 02140, USA
    J Leukoc Biol 88:1171-80. 2010
    b>TBK1 is critical for immunity against microbial pathogens that activate TLR4- and TLR3-dependent signaling pathways. To address the role of TBK1 in inflammation, mice were generated that harbor two copies of a mutant Tbk1 allele...
  70. ncbi Induction of chemokine and cytokine genes in astrocytes following infection with Theiler's murine encephalomyelitis virus is mediated by the Toll-like receptor 3
    Eui Young So
    Department of Microbiology Immunology, Northwestern University Medical School, Chicago, Illinois, USA
    Glia 53:858-67. 2006
    ....
  71. doi The ubiquitin ligase TRIM56 regulates innate immune responses to intracellular double-stranded DNA
    Tetsuo Tsuchida
    Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, Osaka 565 0871, Japan
    Immunity 33:765-76. 2010
    ..This modification induced STING dimerization, which was a prerequisite for recruitment of the antiviral kinase TBK1 and subsequent induction of IFN-β...
  72. ncbi Promoter organization of the interferon-A genes differentially affects virus-induced expression and responsiveness to TBK1 and IKKepsilon
    Ahmet Civas
    UPR 2228 CNRS, Laboratoire de Régulation Transcriptionnelle et Maladies Génétiques, UFR Biomédicale des Saints Pères, Universite Paris V, 45 Rue des Saints Peres, 75270 Paris Cedex 06, France
    J Biol Chem 281:4856-66. 2006
    ..IRF-7, which are activated by phosphorylation during viral infection by the IKK-related serine/threonine kinases TBK1 and IkappaB kinase epsilon (IKKepsilon)...
  73. pmc Polyubiquitin binding to optineurin is required for optimal activation of TANK-binding kinase 1 and production of interferon β
    Catherine E Gleason
    Medical Research Council Protein Phosphorylation Unit, The Sir James Black Centre, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    J Biol Chem 286:35663-74. 2011
    TANK-binding kinase (TBK1) is essential for transcription of the interferon (IFN) β gene in response to lipopolysaccharide (LPS) and double-stranded RNA, but the molecular mechanisms that underlie the activation of TBK1 are incompletely ..
  74. pmc Innate immune recognition of an AT-rich stem-loop DNA motif in the Plasmodium falciparum genome
    Shruti Sharma
    Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA
    Immunity 35:194-207. 2011
    ..Rather, AT-rich DNA sensing involved an unknown receptor that coupled to the STING, TBK1 and IRF3-IRF7 signaling pathway...
  75. doi DNA released from dying host cells mediates aluminum adjuvant activity
    Thomas Marichal
    Laboratory of Cellular and Molecular Physiology, Groupe Interdisciplinaire de Genoproteomique Appliquee, University of Liege, Liege, Belgium
    Nat Med 17:996-1002. 2011
    ....
  76. doi The role of TBK1 and IKKε in the expression and activation of Pellino 1
    Hilary Smith
    MRC Protein Phosphorylation Unit, The Sir James Black Centre, College of Life Sciences, University of Dundee, Dundee, UK
    Biochem J 434:537-48. 2011
    ..and is prevented by inhibition of the IKK [IκB (inhibitor of nuclear factor κB) kinase]-related protein kinases, TBK1 {TANK [TRAF (tumour-necrosis-factor-receptor-associated factor)-associated nuclear factor κB activator]-binding ..
  77. pmc TANK-binding kinase 1 attenuates PTAP-dependent retroviral budding through targeting endosomal sorting complex required for transport-I
    Qi Da
    Key Laboratory of Infection and Immunity, Chinese Academy of Sciences, Institute of Biophysics, Beijing, China
    J Immunol 186:3023-30. 2011
    ..In this study, we demonstrated that TANK-binding kinase 1 (TBK1) directly interacted with VPS37C, a subunit of endosomal sorting complex required for transport-I (ESCRT-I) in the ..
  78. doi Intracellular MHC class II molecules promote TLR-triggered innate immune responses by maintaining activation of the kinase Btk
    Xingguang Liu
    National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai, China
    Nat Immunol 12:416-24. 2011
    ..Then, Btk interacted with the adaptor molecules MyD88 and TRIF and thereby promoted TLR signaling. Therefore, intracellular MHC class II molecules can act as adaptors, promoting full activation of TLR-triggered innate immune responses...