The E3 ligase Itch negatively regulates inflammatory signaling pathways by controlling the function of the ubiquitin-editing enzyme A20.

Abstract:

:The ubiquitin-editing enzyme A20 is a critical negative regulator of inflammation and cytokine-mediated activation of the transcription factor NF-kappaB; however, little is known about the mechanisms of A20-mediated inactivation of signaling intermediates such as RIP1. Here we demonstrate that the regulatory molecule TAX1BP1 recruited the E3 ligase Itch to A20 via two 'PPXY' motifs. Itch was essential for the termination of tumor necrosis factor receptor signaling by controlling A20-mediated recruitment and inactivation of RIP1. Furthermore, the Tax oncoprotein of human T cell leukemia virus type I targeted this complex for inactivation by disrupting the interaction among TAX1BP1, A20 and Itch. Thus, our studies show a previously unappreciated complexity of A20 substrate recognition and inactivation whereby TAX1BP1 and Itch function as essential subunits of an A20 ubiquitin-editing complex.

journal_name

Nat Immunol

journal_title

Nature immunology

authors

Shembade N,Harhaj NS,Parvatiyar K,Copeland NG,Jenkins NA,Matesic LE,Harhaj EW

doi

10.1038/ni1563

subject

Has Abstract

pub_date

2008-03-01 00:00:00

pages

254-62

issue

3

eissn

1529-2908

issn

1529-2916

pii

ni1563

journal_volume

9

pub_type

杂志文章
  • Stimulation of CD25(+)CD4(+) regulatory T cells through GITR breaks immunological self-tolerance.

    abstract::CD25(+)CD4(+) regulatory T cells in normal animals are engaged in the maintenance of immunological self-tolerance. We show here that glucocorticoid-induced tumor necrosis factor receptor family-related gene (GITR, also known as TNFRSF18)--a member of the tumor necrosis factor-nerve growth factor (TNF-NGF) receptor gen...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni759

    authors: Shimizu J,Yamazaki S,Takahashi T,Ishida Y,Sakaguchi S

    更新日期:2002-02-01 00:00:00

  • The ER aminopeptidase ERAP1 enhances or limits antigen presentation by trimming epitopes to 8-9 residues.

    abstract::Endoplasmic reticulum (ER) aminopeptidase 1 (ERAP1) appears to be specialized to produce peptides presented on class I major histocompatibility complex molecules. We found that purified ERAP1 trimmed peptides that were ten residues or longer, but spared eight-residue peptides. In vivo, ERAP1 enhanced production of an ...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni860

    authors: York IA,Chang SC,Saric T,Keys JA,Favreau JM,Goldberg AL,Rock KL

    更新日期:2002-12-01 00:00:00

  • Binding of the Drosophila cytokine Spätzle to Toll is direct and establishes signaling.

    abstract::The extracellular protein Spätzle is required for activation of the Toll signaling pathway in the embryonic development and innate immune defense of Drosophila. Spätzle is synthesized as a pro-protein and is processed to a functional form by a serine protease. We show here that the mature form of Spätzle triggers a To...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni955

    authors: Weber AN,Tauszig-Delamasure S,Hoffmann JA,Lelièvre E,Gascan H,Ray KP,Morse MA,Imler JL,Gay NJ

    更新日期:2003-08-01 00:00:00

  • TCR sequencing paired with massively parallel 3' RNA-seq reveals clonotypic T cell signatures.

    abstract::High-throughput 3' single-cell RNA-sequencing (scRNA-seq) allows cost-effective, detailed characterization of individual immune cells from tissues. Current techniques, however, are limited in their ability to elucidate essential immune cell features, including variable sequences of T cell antigen receptors (TCRs) that...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/s41590-019-0544-5

    authors: Tu AA,Gierahn TM,Monian B,Morgan DM,Mehta NK,Ruiter B,Shreffler WG,Shalek AK,Love JC

    更新日期:2019-12-01 00:00:00

  • The genetics of complex autoimmune diseases: non-MHC susceptibility genes.

    abstract::Susceptibility to complex autoimmune diseases (AIDs) is a multigenic phenotype affected by a variety of genetic and environmental or stochastic factors. After over a decade of linkage analyses, the identification of non-major histocompatibility complex (non-MHC) susceptibility alleles has proved to be difficult, predo...

    journal_title:Nature immunology

    pub_type: 杂志文章,评审

    doi:10.1038/ni0901-802

    authors: Wandstrat A,Wakeland E

    更新日期:2001-09-01 00:00:00

  • Activation of autophagy by inflammatory signals limits IL-1β production by targeting ubiquitinated inflammasomes for destruction.

    abstract::Autophagosomes delivers cytoplasmic constituents to lysosomes for degradation, whereas inflammasomes are molecular platforms activated by infection or stress that regulate the activity of caspase-1 and the maturation of interleukin 1β (IL-1β) and IL-18. Here we show that the induction of AIM2 or NLRP3 inflammasomes in...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.2215

    authors: Shi CS,Shenderov K,Huang NN,Kabat J,Abu-Asab M,Fitzgerald KA,Sher A,Kehrl JH

    更新日期:2012-01-29 00:00:00

  • Chemokine CXCL13 is essential for lymph node initiation and is induced by retinoic acid and neuronal stimulation.

    abstract::The location of embryonic lymph node development is determined by the initial clustering of lymphoid tissue-inducer (LTi) cells. Here we demonstrate that both the chemokine CXCL13 and the chemokine CCL21 attracted LTi cells at embryonic days 12.5-14.5 and that initial clustering depended exclusively on CXCL13. Retinoi...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.1789

    authors: van de Pavert SA,Olivier BJ,Goverse G,Vondenhoff MF,Greuter M,Beke P,Kusser K,Höpken UE,Lipp M,Niederreither K,Blomhoff R,Sitnik K,Agace WW,Randall TD,de Jonge WJ,Mebius RE

    更新日期:2009-11-01 00:00:00

  • T cell sensing of antigen dose governs interactive behavior with dendritic cells and sets a threshold for T cell activation.

    abstract::After homing to lymph nodes, CD8+ T cells are primed by dendritic cells (DCs) in three phases. During phase one, T cells undergo brief serial contacts with DCs for several hours, whereas phase two is characterized by stable T cell-DC interactions. We show here that the duration of phase one and T cell activation kinet...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1559

    authors: Henrickson SE,Mempel TR,Mazo IB,Liu B,Artyomov MN,Zheng H,Peixoto A,Flynn MP,Senman B,Junt T,Wong HC,Chakraborty AK,von Andrian UH

    更新日期:2008-03-01 00:00:00

  • Membrane metalloprotease TRABD2A restricts HIV-1 progeny production in resting CD4+ T cells by degrading viral Gag polyprotein.

    abstract::Resting CD4+ T cells are highly resistant to the production of human immunodeficiency virus type 1 (HIV-1). However, the mechanism by which resting CD4+ T cells restrict such production in the late viral replication phase of infection has remained unclear. In this study, we found that the cell membrane metalloprotease...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/s41590-019-0385-2

    authors: Liang G,Zhao L,Qiao Y,Geng W,Zhang X,Liu M,Dong J,Ding H,Sun H,Shang H

    更新日期:2019-06-01 00:00:00

  • Transcriptomic and epigenetic mechanisms underlying myeloid diversity in the lung.

    abstract::The lung is inhabited by resident alveolar and interstitial macrophages as well as monocytic cells that survey lung tissues. Each cell type plays distinct functional roles under homeostatic and inflammatory conditions, but mechanisms establishing their molecular identities and functional potential remain poorly unders...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/s41590-019-0582-z

    authors: Sajti E,Link VM,Ouyang Z,Spann NJ,Westin E,Romanoski CE,Fonseca GJ,Prince LS,Glass CK

    更新日期:2020-02-01 00:00:00

  • Distinct antibody responses to SARS-CoV-2 in children and adults across the COVID-19 clinical spectrum.

    abstract::Clinical manifestations of COVID-19 caused by the new coronavirus SARS-CoV-2 are associated with age1,2. Adults develop respiratory symptoms, which can progress to acute respiratory distress syndrome (ARDS) in the most severe form, while children are largely spared from respiratory illness but can develop a life-threa...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/s41590-020-00826-9

    authors: Weisberg SP,Connors TJ,Zhu Y,Baldwin MR,Lin WH,Wontakal S,Szabo PA,Wells SB,Dogra P,Gray J,Idzikowski E,Stelitano D,Bovier FT,Davis-Porada J,Matsumoto R,Poon MML,Chait M,Mathieu C,Horvat B,Decimo D,Hudson KE,Zot

    更新日期:2021-01-01 00:00:00

  • IL-25-responsive, lineage-negative KLRG1(hi) cells are multipotential 'inflammatory' type 2 innate lymphoid cells.

    abstract::Innate lymphoid cells (ILCs) are lymphocyte-like cells that lack T cell or B cell antigen receptors and mediate protective and repair functions through cytokine secretion. Among these, type 2 ILCs (ILC2 cells) are able to produce type 2 cytokines. We report the existence of an inflammatory ILC2 (iILC2) population resp...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.3078

    authors: Huang Y,Guo L,Qiu J,Chen X,Hu-Li J,Siebenlist U,Williamson PR,Urban JF Jr,Paul WE

    更新日期:2015-02-01 00:00:00

  • Plasma cell differentiation and the unfolded protein response intersect at the transcription factor XBP-1.

    abstract::The transcription factor X-box binding protein 1 (XBP-1) is essential for the differentiation of plasma cells and the unfolded protein response (UPR). Here we show that UPR-induced splicing of XBP-1 by the transmembrane endonuclease IRE1 is required to restore production of immunoglobulin in XBP-1-/- mouse B cells, pr...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni907

    authors: Iwakoshi NN,Lee AH,Vallabhajosyula P,Otipoby KL,Rajewsky K,Glimcher LH

    更新日期:2003-04-01 00:00:00

  • Prevention of T cell-driven complement activation and inflammation by tryptophan catabolism during pregnancy.

    abstract::Indoleamine 2,3 dioxygenase (IDO) activity during pregnancy protects developing fetuses from maternal immune responses in CBA mice. We show here that fetal allografts were rejected only in mating combinations where paternally inherited tissue antigens elicited potent maternal T cell responses after exposure to IDO inh...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/83183

    authors: Mellor AL,Sivakumar J,Chandler P,Smith K,Molina H,Mao D,Munn DH

    更新日期:2001-01-01 00:00:00

  • Egr-2 and Egr-3 are negative regulators of T cell activation.

    abstract::T cell receptor engagement in the absence of proper accessory signals leads to T cell anergy. E3 ligases are involved in maintaining the anergic state. However, the specific molecules responsible for the induction of anergy have yet to be elucidated. Using microarray analysis we have identified here early growth respo...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1193

    authors: Safford M,Collins S,Lutz MA,Allen A,Huang CT,Kowalski J,Blackford A,Horton MR,Drake C,Schwartz RH,Powell JD

    更新日期:2005-05-01 00:00:00

  • Sensing and alarm function of resident memory CD8⁺ T cells.

    abstract::CD8(+) T cells eliminate intracellular infections through two contact-dependent effector functions: cytolysis and secretion of antiviral cytokines. Here we identify the following additional function for memory CD8(+) T cells that persist at front-line sites of microbial exposure: to serve as local sensors of previousl...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.2568

    authors: Schenkel JM,Fraser KA,Vezys V,Masopust D

    更新日期:2013-05-01 00:00:00

  • Intrusive HIV-1-infected cells.

    abstract::Macrophages infected with human immunodeficiency virus type 1 emit long intercellular conduits that shuttle the viral protein Nef to bystander B cells, where it impairs cellular function and immunoglobulin class switching. ...

    journal_title:Nature immunology

    pub_type: 新闻

    doi:10.1038/ni0909-933

    authors: Rudnicka D,Schwartz O

    更新日期:2009-09-01 00:00:00

  • The IκB kinase complex regulates the stability of cytokine-encoding mRNA induced by TLR-IL-1R by controlling degradation of regnase-1.

    abstract::Toll-like receptor (TLR) signaling activates the inhibitor of transcription factor NF-κB (IκB) kinase (IKK) complex, which governs NF-κB-mediated transcription during inflammation. The RNase regnase-1 serves a critical role in preventing autoimmunity by controlling the stability of mRNAs that encode cytokines. Here we...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.2137

    authors: Iwasaki H,Takeuchi O,Teraguchi S,Matsushita K,Uehata T,Kuniyoshi K,Satoh T,Saitoh T,Matsushita M,Standley DM,Akira S

    更新日期:2011-10-30 00:00:00

  • Mechanisms and consequences of Jak-STAT signaling in the immune system.

    abstract::Kinases of the Jak ('Janus kinase') family and transcription factors (TFs) of the STAT ('signal transducer and activator of transcription') family constitute a rapid membrane-to-nucleus signaling module that affects every aspect of the mammalian immune system. Research on this paradigmatic pathway has experienced brea...

    journal_title:Nature immunology

    pub_type: 杂志文章,评审

    doi:10.1038/ni.3691

    authors: Villarino AV,Kanno Y,O'Shea JJ

    更新日期:2017-03-22 00:00:00

  • Nonspecific effects of neonatal and infant vaccination: public-health, immunological and conceptual challenges.

    abstract::Vaccines can have nonspecific effects through their modulation of responses to infections not specifically targeted by the vaccine. However, lack of knowledge about the underlying immunological mechanisms and molecular cause-and-effect relationships prevent use of this potentially powerful early-life intervention to i...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.2961

    authors: Aaby P,Kollmann TR,Benn CS

    更新日期:2014-10-01 00:00:00

  • CCL19-CCR7-dependent reverse transendothelial migration of myeloid cells clears Chlamydia muridarum from the arterial intima.

    abstract::Regions of the normal arterial intima predisposed to atherosclerosis are sites of ongoing monocyte trafficking and also contain resident myeloid cells with features of dendritic cells. However, the pathophysiological roles of these cells are poorly understood. Here we found that intimal myeloid cells underwent reverse...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.3564

    authors: Roufaiel M,Gracey E,Siu A,Zhu SN,Lau A,Ibrahim H,Althagafi M,Tai K,Hyduk SJ,Cybulsky KO,Ensan S,Li A,Besla R,Becker HM,Xiao H,Luther SA,Inman RD,Robbins CS,Jongstra-Bilen J,Cybulsky MI

    更新日期:2016-11-01 00:00:00

  • The zinc-finger protein MAZR is part of the transcription factor network that controls the CD4 versus CD8 lineage fate of double-positive thymocytes.

    abstract::The CD4 versus CD8 lineage specification of thymocytes is linked to coreceptor expression. The transcription factor MAZR has been identified as an important regulator of Cd8 expression. Here we show that variegated CD8 expression by loss of Cd8 enhancers was reverted in MAZR-deficient mice, which confirms that MAZR ne...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.1860

    authors: Sakaguchi S,Hombauer M,Bilic I,Naoe Y,Schebesta A,Taniuchi I,Ellmeier W

    更新日期:2010-05-01 00:00:00

  • CEACAM1 inhibits Toll-like receptor 2-triggered antibacterial responses of human pulmonary epithelial cells.

    abstract::Although Moraxella catarrhalis and Neisseria meningitidis are important human pathogens, they often colonize the human respiratory tract without causing overt clinical symptoms. Both pathogens express structurally unrelated proteins that share the ability to stimulate the adhesion molecule CEACAM1 expressed on human c...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.1661

    authors: Slevogt H,Zabel S,Opitz B,Hocke A,Eitel J,N'guessan PD,Lucka L,Riesbeck K,Zimmermann W,Zweigner J,Temmesfeld-Wollbrueck B,Suttorp N,Singer BB

    更新日期:2008-11-01 00:00:00

  • Monocytes-macrophages that express α-smooth muscle actin preserve primitive hematopoietic cells in the bone marrow.

    abstract::Hematopoietic stem and progenitor cells (HSPCs) are regulated by various bone marrow stromal cell types. Here we identified rare activated bone marrow monocytes and macrophages with high expression of α-smooth muscle actin (α-SMA) and the cyclooxygenase COX-2 that were adjacent to primitive HSPCs. These myeloid cells ...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.2408

    authors: Ludin A,Itkin T,Gur-Cohen S,Mildner A,Shezen E,Golan K,Kollet O,Kalinkovich A,Porat Z,D'Uva G,Schajnovitz A,Voronov E,Brenner DA,Apte RN,Jung S,Lapidot T

    更新日期:2012-11-01 00:00:00

  • Disturbed mitochondrial dynamics in CD8+ TILs reinforce T cell exhaustion.

    abstract::The metabolic challenges present in tumors attenuate the metabolic fitness and antitumor activity of tumor-infiltrating T lymphocytes (TILs). However, it remains unclear whether persistent metabolic insufficiency can imprint permanent T cell dysfunction. We found that TILs accumulated depolarized mitochondria as a res...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/s41590-020-0793-3

    authors: Yu YR,Imrichova H,Wang H,Chao T,Xiao Z,Gao M,Rincon-Restrepo M,Franco F,Genolet R,Cheng WC,Jandus C,Coukos G,Jiang YF,Locasale JW,Zippelius A,Liu PS,Tang L,Bock C,Vannini N,Ho PC

    更新日期:2020-12-01 00:00:00

  • Lack of prominent peptide-major histocompatibility complex features limits repertoire diversity in virus-specific CD8+ T cell populations.

    abstract::Using both 'reverse genetics' and structural analysis, we have examined the in vivo relationship between antigenicity and T cell receptor (TCR) repertoire diversity. Influenza A virus infection of C57BL/6 mice induces profoundly different TCR repertoires specific for the nucleoprotein peptide of amino acids 366-374 (N...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1175

    authors: Turner SJ,Kedzierska K,Komodromou H,La Gruta NL,Dunstone MA,Webb AI,Webby R,Walden H,Xie W,McCluskey J,Purcell AW,Rossjohn J,Doherty PC

    更新日期:2005-04-01 00:00:00

  • Visualizing dendritic cell networks in vivo.

    abstract::In the steady state, dendritic cells (DCs) in the lymph node induce T cell tolerance to self antigens. Innate signals trigger the maturation of tissue DCs, which migrate into lymph nodes and activate T cells. To examine DCs in vivo, we produced transgenic mice whose DCs expressed enhanced yellow fluorescent protein. T...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1139

    authors: Lindquist RL,Shakhar G,Dudziak D,Wardemann H,Eisenreich T,Dustin ML,Nussenzweig MC

    更新日期:2004-12-01 00:00:00

  • Chd4 choreographs self-antigen expression for central immune tolerance.

    abstract::Autoreactive T cells are eliminated in the thymus to prevent autoimmunity by promiscuous expression of tissue-restricted self-antigens in medullary thymic epithelial cells. This expression is dependent on the transcription factor Fezf2, as well as the transcriptional regulator Aire, but the entire picture of the trans...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/s41590-020-0717-2

    authors: Tomofuji Y,Takaba H,Suzuki HI,Benlaribi R,Martinez CDP,Abe Y,Morishita Y,Okamura T,Taguchi A,Kodama T,Takayanagi H

    更新日期:2020-08-01 00:00:00

  • Medullary thymic epithelial cells expressing Aire represent a unique lineage derived from cells expressing claudin.

    abstract::The autoimmune regulator Aire is expressed in a small proportion of medullary thymic epithelial cells (mTECs) and is crucial in the induction of central T cell tolerance. The origin and development of Aire(+) mTECs, however, are not well understood. Here we demonstrate that the tight-junction components claudin-3 and ...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1438

    authors: Hamazaki Y,Fujita H,Kobayashi T,Choi Y,Scott HS,Matsumoto M,Minato N

    更新日期:2007-03-01 00:00:00

  • Tissue-resident macrophages.

    abstract::Tissue-resident macrophages are a heterogeneous population of immune cells that fulfill tissue-specific and niche-specific functions. These range from dedicated homeostatic functions, such as clearance of cellular debris and iron processing, to central roles in tissue immune surveillance, response to infection and the...

    journal_title:Nature immunology

    pub_type: 杂志文章,评审

    doi:10.1038/ni.2705

    authors: Davies LC,Jenkins SJ,Allen JE,Taylor PR

    更新日期:2013-10-01 00:00:00