Cell type-specific function of TAK1 in innate immune signaling.

Transforming growth factor β-activated kinase 1 (TAK1 or MAP3K7) is a key signaling component of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Activation of TAK1 is tightly regulated through its binding partners and protein modifications. Although TAK1 functions as an essential and positive regulator of innate immune signaling and apoptosis in mouse embryonic fibroblasts (MEFs), T cells, and other cells, it negatively regulates cell development and activation of proinflammatory signaling pathways in neutrophils. However, the molecular mechanisms responsible for the opposite roles of TAK1 in different cell types remain to be addressed. In this article, we discuss the latest progresses in our understanding of TAK1 regulation, function, and mechanisms in a cell-type specific manner.

[1]  C. M. Owens,et al.  The cytoplasmic body component TRIM5α restricts HIV-1 infection in Old World monkeys , 2004, Nature.

[2]  H. Shu,et al.  Tripartite motif 8 (TRIM8) modulates TNFα- and IL-1β–triggered NF-κB activation by targeting TAK1 for K63-linked polyubiquitination , 2011, Proceedings of the National Academy of Sciences.

[3]  Zhijian J. Chen,et al.  Ubiquitin-mediated activation of TAK1 and IKK , 2007, Oncogene.

[4]  D. V. van Aalten,et al.  O-GlcNAcylation of TAB1 modulates TAK1-mediated cytokine release , 2010, The EMBO journal.

[5]  J. Qin,et al.  Lys48-linked TAK1 polyubiquitination at lysine-72 downregulates TNFα-induced NF-κB activation via mediating TAK1 degradation. , 2012, Cellular signalling.

[6]  Songbin Fu,et al.  TAK1 lysine 158 is required for TGF-β-induced TRAF6-mediated Smad-independent IKK/NF-κB and JNK/AP-1 activation. , 2011, Cellular signalling.

[7]  M. O’Connor,et al.  The TGFβ activated kinase TAK1 regulates vascular development in vivo , 2006 .

[8]  Zhijian J. Chen,et al.  TAB2 and TAB3 activate the NF-kappaB pathway through binding to polyubiquitin chains. , 2004, Molecular cell.

[9]  Min Yu,et al.  TAK1 Inhibition Promotes Apoptosis in KRAS-Dependent Colon Cancers , 2012, Cell.

[10]  Michael D. Schneider,et al.  A pivotal role for endogenous TGF-β-activated kinase-1 in the LKB1/AMP-activated protein kinase energy-sensor pathway , 2006, Proceedings of the National Academy of Sciences.

[11]  M. Hoenerhoff,et al.  Inhibition of transforming growth factor-β-activated kinase-1 blocks cancer cell adhesion, invasion, and metastasis , 2012, British Journal of Cancer.

[12]  J. Ninomiya-Tsuji,et al.  Generation of a conditional mutant allele for Tab1 in mouse , 2008, Genesis.

[13]  E. Chun,et al.  Reciprocal Inhibition between the Transforming Growth Factor-β-activated Kinase 1 (TAK1) and Apoptosis Signal-regulating Kinase 1 (ASK1) Mitogen-activated Protein Kinase Kinase Kinases and Its Suppression by TAK1-binding Protein 2 (TAB2), an Adapter Protein for TAK1* , 2011, The Journal of Biological Chemistry.

[14]  S. Akira,et al.  Two Mechanistically and Temporally Distinct NF-κB Activation Pathways in IL-1 Signaling , 2009, Science Signaling.

[15]  Jiahuai Han,et al.  MAPKK-Independent Activation of p38α Mediated by TAB1-Dependent Autophosphorylation of p38α , 2002, Science.

[16]  Michael D. Schneider,et al.  Deletion of TAK1 in the Myeloid Lineage Results in the Spontaneous Development of Myelomonocytic Leukemia in Mice , 2012, PloS one.

[17]  C. Weston,et al.  The JNK signal transduction pathway. , 2007, Current opinion in genetics & development.

[18]  J. Whisstock,et al.  The Type III Effectors NleE and NleB from Enteropathogenic E. coli and OspZ from Shigella Block Nuclear Translocation of NF-κB p65 , 2010, PLoS pathogens.

[19]  D. Green,et al.  Suppression of TNF-alpha-induced apoptosis by NF-kappaB. , 1996, Science.

[20]  D. Ferrari,et al.  Apoptosis signaling by death receptors. , 1998, European journal of biochemistry.

[21]  C. Fortin,et al.  Constitutive Association of TGF-β–Activated Kinase 1 with the IκB Kinase Complex in the Nucleus and Cytoplasm of Human Neutrophils and Its Impact on Downstream Processes , 2010, The Journal of Immunology.

[22]  L. Fitzpatrick,et al.  Deubiquitinating enzyme CYLD negatively regulates the ubiquitin-dependent kinase Tak1 and prevents abnormal T cell responses , 2007, The Journal of experimental medicine.

[23]  Zhijian J. Chen,et al.  Direct Activation of Protein Kinases by Unanchored Polyubiquitin Chains , 2009, Nature.

[24]  K. Irie,et al.  TAB1: An Activator of the TAK1 MAPKKK in TGF-β Signal Transduction , 1996, Science.

[25]  S. Akira,et al.  TAK1 Is a Master Regulator of Epidermal Homeostasis Involving Skin Inflammation and Apoptosis* , 2006, Journal of Biological Chemistry.

[26]  Michael D. Schneider,et al.  Essential role of TAK1 in thymocyte development and activation. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[27]  R. Schwabe,et al.  Mechanisms of Liver Injury. I. TNF-alpha-induced liver injury: role of IKK, JNK, and ROS pathways. , 2006, American journal of physiology. Gastrointestinal and liver physiology.

[28]  E. Abraham,et al.  Involvement of Reactive Oxygen Species in Toll-Like Receptor 4-Dependent Activation of NF-κB 1 , 2004, The Journal of Immunology.

[29]  Yi Lu,et al.  Interleukin-1 (IL-1)-induced TAK1-dependent Versus MEKK3-dependent NFκB Activation Pathways Bifurcate at IL-1 Receptor-associated Kinase Modification* , 2007, Journal of Biological Chemistry.

[30]  M. Karin Nuclear factor-κB in cancer development and progression , 2006, Nature.

[31]  M. Xie,et al.  Phosphorylation of Thr-178 and Thr-184 in the TAK1 T-loop Is Required for Interleukin (IL)-1-mediated Optimal NFκB and AP-1 Activation as Well as IL-6 Gene Expression* , 2008, Journal of Biological Chemistry.

[32]  Songbin Fu,et al.  USP4 targets TAK1 to downregulate TNFα-induced NF-κB activation , 2011, Cell Death and Differentiation.

[33]  Jay K Kolls,et al.  The Biological Functions of T Helper 17 Cell Effector Cytokines in Inflammation , 2022 .

[34]  B. Su,et al.  TAK1 negatively regulates NF-κB and p38 MAP kinase activation in Gr-1+CD11b+ neutrophils. , 2012, Immunity.

[35]  S. Akira,et al.  Enterocyte-Derived TAK1 Signaling Prevents Epithelium Apoptosis and the Development of Ileitis and Colitis1 , 2008, The Journal of Immunology.

[36]  Jianfeng Xu,et al.  Deletion of a Small Consensus Region at 6q15, Including the MAP3K7 Gene, Is Significantly Associated with High-Grade Prostate Cancers , 2007, Clinical Cancer Research.

[37]  David A. Brenner,et al.  Mechanisms of Liver Injury. I. TNF-α-induced liver injury: role of IKK, JNK, and ROS pathways , 2006 .

[38]  Helen Y Wang,et al.  Toll-like receptors and immune regulation: implications for cancer therapy , 2008, Oncogene.

[39]  Jianfeng Xu,et al.  Suppression of Tak1 promotes prostate tumorigenesis. , 2012, Cancer research.

[40]  Jiwang Zhang,et al.  Transforming Growth Factor--activated Kinase 1 Regulates Natural Killer Cell-mediated Cytotoxicity and Cytokine , 2011 .

[41]  H. Sakurai,et al.  Critical Roles of Threonine 187 Phosphorylation in Cellular Stress-induced Rapid and Transient Activation of Transforming Growth Factor-β-activated Kinase 1 (TAK1) in a Signaling Complex Containing TAK1-binding Protein TAB1 and TAB2* , 2005, Journal of Biological Chemistry.

[42]  M. Carlson,et al.  Mammalian TAK1 Activates Snf1 Protein Kinase in Yeast and Phosphorylates AMP-activated Protein Kinase in Vitro* , 2006, Journal of Biological Chemistry.

[43]  K. Irie,et al.  TAB1: an activator of the TAK1 MAPKKK in TGF-beta signal transduction. , 1996, Science.

[44]  E. Reddy,et al.  Modulation of life and death by the TNF receptor superfamily , 1998, Oncogene.

[45]  J. Ninomiya-Tsuji,et al.  TAK1 kinase signaling regulates embryonic angiogenesis by modulating endothelial cell survival and migration. , 2012, Blood.

[46]  D. Golenbock,et al.  YopJ targets TRAF proteins to inhibit TLR‐mediated NF‐κB, MAPK and IRF3 signal transduction , 2007, Cellular microbiology.

[47]  S. Akira,et al.  TAK1 is indispensable for development of T cells and prevention of colitis by the generation of regulatory T cells. , 2006, International immunology.

[48]  Honglin Zhou,et al.  Yersinia virulence factor YopJ acts as a deubiquitinase to inhibit NF-κB activation , 2005, The Journal of experimental medicine.

[49]  Kunihiro Matsumoto,et al.  The Yersinia enterocolitica effector YopP inhibits host cell signalling by inactivating the protein kinase TAK1 in the IL‐1 signalling pathway , 2006, EMBO reports.

[50]  A. Brivanlou,et al.  Gene profiling during neural induction in Xenopus laevis: regulation of BMP signaling by post-transcriptional mechanisms and TAB3, a novel TAK1-binding protein , 2002, Development.

[51]  A. Zychlinsky,et al.  Neutrophil function: from mechanisms to disease. , 2012, Annual review of immunology.

[52]  Jiwang Zhang,et al.  TNF-α/Fas-RIP-1-induced cell death signaling separates murine hematopoietic stem cells/progenitors into 2 distinct populations. , 2011, Blood.

[53]  J. Ninomiya-Tsuji,et al.  Protein Phosphatase 6 Down-regulates TAK1 Kinase Activation in the IL-1 Signaling Pathway* , 2006, Journal of Biological Chemistry.

[54]  J. Hugot,et al.  Yersinia pseudotuberculosis effector YopJ subverts the Nod2/RICK/TAK1 pathway and activates caspase-1 to induce intestinal barrier dysfunction. , 2012, Cell host & microbe.

[55]  P. Cohen,et al.  TAB3, a new binding partner of the protein kinase TAK1. , 2004, The Biochemical journal.

[56]  H. Sakurai Targeting of TAK1 in inflammatory disorders and cancer. , 2012, Trends in pharmacological sciences.

[57]  R. Gaynor,et al.  Role of the TAB2‐related protein TAB3 in IL‐1 and TNF signaling , 2003, The EMBO journal.

[58]  S. Akira,et al.  Disruption of TAK1 in hepatocytes causes hepatic injury, inflammation, fibrosis, and carcinogenesis , 2009, Proceedings of the National Academy of Sciences.

[59]  S. Akira,et al.  TAB2 Is Essential for Prevention of Apoptosis in Fetal Liver but Not for Interleukin-1 Signaling , 2003, Molecular and Cellular Biology.

[60]  Ki-Young Lee,et al.  TAK1, but not TAB1 or TAB2, plays an essential role in multiple signaling pathways in vivo. , 2005, Genes & development.

[61]  Hong-Hsing Liu,et al.  A critical role of TAK1 in B-cell receptor-mediated nuclear factor kappaB activation. , 2009, Blood.

[62]  David Baltimore,et al.  An Essential Role for NF-κB in Preventing TNF-α-Induced Cell Death , 1996, Science.

[63]  Hisayuki Nomiyama,et al.  Regulation of the Interleukin-1-induced Signaling Pathways by a Novel Member of the Protein Phosphatase 2C Family (PP2Cε)* , 2003, The Journal of Biological Chemistry.

[64]  F. Rus,et al.  Serine/threonine acetylation of TGFβ-activated kinase (TAK1) by Yersinia pestis YopJ inhibits innate immune signaling , 2012, Proceedings of the National Academy of Sciences.

[65]  Xin-yu Liu,et al.  TAK1, more than just innate immunity , 2012, IUBMB life.

[66]  L. Norton,et al.  Tumor entrained neutrophils inhibit seeding in the premetastatic lung. , 2011, Cancer cell.

[67]  H. Chi,et al.  Transforming growth factor beta-activated kinase 1 (TAK1)-dependent checkpoint in the survival of dendritic cells promotes immune homeostasis and function , 2012, Proceedings of the National Academy of Sciences.

[68]  Seamus J. Martin,et al.  Suppression of TNF-α-Induced Apoptosis by NF-κB , 1996, Science.

[69]  Lin-Feng Chen,et al.  Helicobacter pylori CagA activates NF‐κB by targeting TAK1 for TRAF6‐mediated Lys 63 ubiquitination , 2009, EMBO reports.

[70]  C. Heldin,et al.  The type I TGF-β receptor engages TRAF6 to activate TAK1 in a receptor kinase-independent manner , 2008, Nature Cell Biology.

[71]  Michael D. Schneider,et al.  The kinase TAK1 integrates antigen and cytokine receptor signaling for T cell development, survival and function , 2006, Nature Immunology.

[72]  D. Baltimore,et al.  An essential role for NF-kappaB in preventing TNF-alpha-induced cell death. , 1996, Science.

[73]  Min Xie,et al.  TAK1 is an essential regulator of BMP signalling in cartilage , 2009, The EMBO journal.

[74]  Thomas J. Fuchs,et al.  TAK1 suppresses a NEMO-dependent but NF-kappaB-independent pathway to liver cancer. , 2010, Cancer cell.

[75]  J. Chen,et al.  Cysteine methylation disrupts ubiquitin-chain sensing in NF-κB activation , 2011, Nature.

[76]  Jiahuai Han,et al.  MAPKK-independent activation of p38alpha mediated by TAB1-dependent autophosphorylation of p38alpha. , 2002, Science.

[77]  Ramon F. Thali,et al.  Autoactivation of Transforming Growth Factor β-activated Kinase 1 Is a Sequential Bimolecular Process* , 2010, The Journal of Biological Chemistry.

[78]  M. O’Connor,et al.  The TGF beta activated kinase TAK1 regulates vascular development in vivo. , 2006, Development.

[79]  R. Chen,et al.  The Dual-specificity Phosphatase DUSP14 Negatively Regulates Tumor Necrosis Factor- and Interleukin-1-induced Nuclear Factor-κB Activation by Dephosphorylating the Protein Kinase TAK1* , 2012, The Journal of Biological Chemistry.

[80]  J. Tschopp,et al.  NLRP3 inflammasome activation: the convergence of multiple signalling pathways on ROS production? , 2010, Nature Reviews Immunology.

[81]  Keisuke Ito,et al.  Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells , 2006, Nature Medicine.

[82]  G. Sen,et al.  A critical role for IRAK4 kinase activity in Toll-like receptor–mediated innate immunity , 2007, The Journal of experimental medicine.

[83]  G. Kollias,et al.  Correction: Myeloid Takl Acts as a Negative Regulator of the LPS Response and Mediates Resistance to Endotoxemia , 2012, PLoS ONE.

[84]  A. Younes,et al.  Essential role of TAK1 in regulating mantle cell lymphoma survival. , 2012, Blood.

[85]  S. Akira,et al.  Essential function for the kinase TAK1 in innate and adaptive immune responses , 2005, Nature Immunology.

[86]  N. Chandel,et al.  Mitochondrial ROS initiate phosphorylation of p38 MAP kinase during hypoxia in cardiomyocytes. , 2002, American journal of physiology. Lung cellular and molecular physiology.

[87]  M. Karin Nuclear factor-kappaB in cancer development and progression. , 2006, Nature.

[88]  A. López-Rivas,et al.  TAK1 activates AMPK‐dependent cytoprotective autophagy in TRAIL‐treated epithelial cells , 2009, The EMBO journal.

[89]  J. Ninomiya-Tsuji,et al.  Intestinal Epithelial-Derived TAK1 Signaling Is Essential for Cytoprotection against Chemical-Induced Colitis , 2009, PloS one.

[90]  J. Ninomiya-Tsuji,et al.  Epithelial transforming growth factor β-activated kinase 1 (TAK1) is activated through two independent mechanisms and regulates reactive oxygen species , 2012, Proceedings of the National Academy of Sciences.

[91]  J. Ninomiya-Tsuji,et al.  Regulation of the TAK1 Signaling Pathway by Protein Phosphatase 2C* , 2001, The Journal of Biological Chemistry.

[92]  G. Cheng,et al.  Polarization of tumor-associated neutrophil phenotype by TGF-beta: "N1" versus "N2" TAN. , 2009, Cancer cell.

[93]  J. Ninomiya-Tsuji,et al.  The kinase TAK1 can activate the NIK-IκB as well as the MAP kinase cascade in the IL-1 signalling pathway , 1999, Nature.

[94]  J. Massagué TGF-beta signal transduction. , 1998, Annual review of biochemistry.

[95]  K. Irie,et al.  TAB2, a novel adaptor protein, mediates activation of TAK1 MAPKKK by linking TAK1 to TRAF6 in the IL-1 signal transduction pathway. , 2000, Molecular cell.

[96]  R. Flavell,et al.  Abstract 5395: The E3 ligase Itch and deubiquitinase Cyld act together to regulate Tak1 and inflammation , 2012 .

[97]  P. Cohen,et al.  Feedback control of the protein kinase TAK1 by SAPK2a/p38α , 2003, The EMBO journal.

[98]  J. Mizukami,et al.  Phosphorylation‐dependent activation of TAK1 mitogen‐activated protein kinase kinase kinase by TAB1 , 2000, FEBS letters.

[99]  Zhijian J. Chen,et al.  Reconstitution of the RIG-I Pathway Reveals a Signaling Role of Unanchored Polyubiquitin Chains in Innate Immunity , 2010, Cell.

[100]  Yang Yu,et al.  TAK1 Lys-158 but not Lys-209 is required for IL-1β-induced Lys63-linked TAK1 polyubiquitination and IKK/NF-κB activation. , 2011, Cellular signalling.

[101]  J. Ninomiya-Tsuji,et al.  Ablation of TAK1 upregulates reactive oxygen species and selectively kills tumor cells. , 2010, Cancer research.

[102]  K. Irie,et al.  Identification of a Member of the MAPKKK Family as a Potential Mediator of TGF-β Signal Transduction , 1995, Science.

[103]  A. Jermy Antiviral immunity: TRIM5 moonlights as a pattern recognition receptor , 2011, Nature Reviews Microbiology.

[104]  S. Akira,et al.  TAK1 is required for the survival of hematopoietic cells and hepatocytes in mice , 2008, The Journal of experimental medicine.

[105]  J. Ninomiya-Tsuji,et al.  TAK1 Regulates Reactive Oxygen Species and Cell Death in Keratinocytes, Which Is Essential for Skin Integrity* , 2008, Journal of Biological Chemistry.

[106]  T. Meyer,et al.  The Type III Secretion Effector NleE Inhibits NF-κB Activation , 2010, PLoS pathogens.

[107]  Zhijian J. Chen,et al.  TAK1 is a ubiquitin-dependent kinase of MKK and IKK , 2001, Nature.

[108]  J. Ninomiya-Tsuji,et al.  TAK1-binding Protein 1, TAB1, Mediates Osmotic Stress-induced TAK1 Activation but Is Dispensable for TAK1-mediated Cytokine Signaling* , 2008, Journal of Biological Chemistry.

[109]  Kunihiro Matsumoto,et al.  ROS-dependent activation of the TRAF6-ASK1-p38 pathway is selectively required for TLR4-mediated innate immunity , 2005, Nature Immunology.

[110]  J. Luban TRIM5 and the Regulation of HIV-1 Infectivity , 2012, Molecular biology international.

[111]  J. Qin,et al.  Lysine 63-linked Polyubiquitination of TAK1 at Lysine 158 Is Required for Tumor Necrosis Factor α- and Interleukin-1β-induced IKK/NF-κB and JNK/AP-1 Activation* , 2009, The Journal of Biological Chemistry.

[112]  W. Toriumi,et al.  Functional Interactions of Transforming Growth Factor β-activated Kinase 1 with IκB Kinases to Stimulate NF-κB Activation* , 1999, The Journal of Biological Chemistry.

[113]  J. Ninomiya-Tsuji,et al.  TGF-β–Activated Kinase 1 Signaling Maintains Intestinal Integrity by Preventing Accumulation of Reactive Oxygen Species in the Intestinal Epithelium , 2010, The Journal of Immunology.

[114]  R. Seth,et al.  Ubiquitin, TAK1 and IKK: is there a connection? , 2006, Cell Death and Differentiation.