TMEM203 is a binding partner and regulator of STING-mediated inflammatory signaling in macrophages.

Abstract:

:Regulation of IFN signaling is critical in host recognition and response to pathogens while its dysregulation underlies the pathogenesis of several chronic diseases. STimulator of IFN Genes (STING) has been identified as a critical mediator of IFN inducing innate immune pathways, but little is known about direct coregulators of this protein. We report here that TMEM203, a conserved putative transmembrane protein, is an intracellular regulator of STING-mediated signaling. We show that TMEM203 interacts, functionally cooperates, and comigrates with STING following cell stimulation, which in turn leads to the activation of the kinase TBK1, and the IRF3 transcription factor. This induces target genes in macrophages, including IFN-β. Using Tmem203 knockout bone marrow-derived macrophages and transient knockdown of TMEM203 in human monocyte-derived macrophages, we show that TMEM203 protein is required for cGAMP-induced STING activation. Unlike STING, TMEM203 mRNA levels are elevated in T cells from patients with systemic lupus erythematosus, a disease characterized by the overexpression of type I interferons. Moreover, TMEM203 mRNA levels are associated with disease activity, as assessed by serum levels of the complement protein C3. Identification of TMEM203 sheds light into the control of STING-mediated innate immune responses, providing a potential novel mechanism for therapeutic interventions in STING-associated inflammatory diseases.

authors

Li Y,James SJ,Wyllie DH,Wynne C,Czibula A,Bukhari A,Pye K,Bte Mustafah SM,Fajka-Boja R,Szabo E,Angyal A,Hegedus Z,Kovacs L,Hill AVS,Jefferies CA,Wilson HL,Yongliang Z,Kiss-Toth E

doi

10.1073/pnas.1901090116

subject

Has Abstract

pub_date

2019-08-13 00:00:00

pages

16479-16488

issue

33

eissn

0027-8424

issn

1091-6490

pii

1901090116

journal_volume

116

pub_type

杂志文章
  • Activation of Na+/H+ exchange in cultured fibroblasts: synergism and antagonism between phorbol ester, Ca2+ ionophore, and growth factors.

    abstract::The effects of phorbol 12-myristate 13-acetate (PMA), a potent activator of protein kinase C, on Na+ influx were investigated in cultured human foreskin fibroblasts (HSWP cells). We report here that in serum-deprived HSWP cells the addition of PMA alone has no significant effect on Na+ influx. However, the addition of...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.82.23.8053

    authors: Vicentini LM,Villereal ML

    更新日期:1985-12-01 00:00:00

  • Stationary spherical vortices in a perfect fluid.

    abstract::Necessary conditions are derived for a spherical vortex in a perfect fluid to be stationary in the case when the velocities depend on a single surface harmonic. The motion is indeterminate unless an additional condition is imposed. In the case when this condition is incompressibility, the equations are solved, yieldin...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.69.9.2460

    authors: Pekeris CL

    更新日期:1972-09-01 00:00:00

  • Adenosine acts by A1 receptors to stimulate release of prolactin from anterior-pituitaries in vitro.

    abstract::Adenosine has been identified in the anterior pituitary gland and is secreted from cultured folliculostellate (FS) cells. To determine whether adenosine controls the secretion of anterior pituitary hormones in vitro, adenosine was incubated with anterior pituitaries. It stimulated prolactin (PRL) release at the lowest...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.13.7795

    authors: Yu WH,Kimura M,Walczewska A,Porter JC,McCann SM

    更新日期:1998-06-23 00:00:00

  • Molecular definition of bovine argininosuccinate synthetase deficiency.

    abstract::Citrullinemia is an inborn error of metabolism due to deficiency of the urea cycle enzyme, argininosuccinate synthetase [L-citrulline:L-aspartate ligase (AMP-forming), EC 6.3.4.5]. The disease was first described in humans but was recently reported in dairy cattle in Australia. Here we report the nucleotide sequence o...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.86.20.7947

    authors: Dennis JA,Healy PJ,Beaudet AL,O'Brien WE

    更新日期:1989-10-01 00:00:00

  • Dynamic bookmarking of primary response genes by p300 and RNA polymerase II complexes.

    abstract::Profiling the dynamic interaction of p300 with proximal promoters of human T cells identified a class of genes that rapidly coassemble p300 and RNA polymerase II (pol II) following mitogen stimulation. Several of these p300 targets are immediate early genes, including FOS, implicating a prominent role for p300 in the ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0905469106

    authors: Byun JS,Wong MM,Cui W,Idelman G,Li Q,De Siervi A,Bilke S,Haggerty CM,Player A,Wang YH,Thirman MJ,Kaberlein JJ,Petrovas C,Koup RA,Longo D,Ozato K,Gardner K

    更新日期:2009-11-17 00:00:00

  • Transcriptionally repressed genes become aberrantly methylated and distinguish tumors of different lineages in breast cancer.

    abstract::Aberrant promoter hypermethylation is frequently observed in cancer. The potential for this mechanism to contribute to tumor development depends on whether the genes affected are repressed because of their methylation. Many aberrantly methylated genes play important roles in development and are bivalently marked in ES...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1013224108

    authors: Sproul D,Nestor C,Culley J,Dickson JH,Dixon JM,Harrison DJ,Meehan RR,Sims AH,Ramsahoye BH

    更新日期:2011-03-15 00:00:00

  • Translocation of a functional protein by a voltage-dependent ion channel.

    abstract::The voltage-dependent gating of the colicin channel involves a substantial structural rearrangement that results in the transfer of about 35% of the 200 residues in its pore-forming domain across the membrane. This transfer appears to represent an unusual type of protein translocation that does not depend on a large, ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.022480199

    authors: Slatin SL,Nardi A,Jakes KS,Baty D,Duché D

    更新日期:2002-02-05 00:00:00

  • The integrin alpha4beta7 forms a complex with cell-surface CD4 and defines a T-cell subset that is highly susceptible to infection by HIV-1.

    abstract::Both activated and resting CD4(+) T cells in mucosal tissues play important roles in the earliest phases of infection after sexual transmission of HIV-1, a process that is inefficient. HIV-1 gp120 binds to integrin alpha(4)beta(7) (alpha(4)beta(7)), the gut mucosal homing receptor. We find that alpha(4)beta(7)(high) C...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0911796106

    authors: Cicala C,Martinelli E,McNally JP,Goode DJ,Gopaul R,Hiatt J,Jelicic K,Kottilil S,Macleod K,O'Shea A,Patel N,Van Ryk D,Wei D,Pascuccio M,Yi L,McKinnon L,Izulla P,Kimani J,Kaul R,Fauci AS,Arthos J

    更新日期:2009-12-08 00:00:00

  • Efficient and stable expression of recombinant fibronectin polypeptides.

    abstract::We describe retroviral expression vectors containing cDNAs encoding part of fibronectin preceded by the signal and "pro" sequences of parathyroid hormone. The recombinant retroviruses were used to generate NIH 3T3 cell lines stably producing functionally active fragments of fibronectin. The recombinant fibronectins (d...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.84.3.754

    authors: Schwarzbauer JE,Mulligan RC,Hynes RO

    更新日期:1987-02-01 00:00:00

  • Single dopaminergic neurons that modulate aggression in Drosophila.

    abstract::Monoamines, including dopamine (DA), have been linked to aggression in various species. However, the precise role or roles served by the amine in aggression have been difficult to define because dopaminergic systems influence many behaviors, and all can be altered by changing the function of dopaminergic neurons. In t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1303446110

    authors: Alekseyenko OV,Chan YB,Li R,Kravitz EA

    更新日期:2013-04-09 00:00:00

  • Prediction of an U2S3-type polymorph of Al2O3 at 3.7 Mbar.

    abstract::We predict by first principles a phase transition in alumina at approximately 3.7 Mbar and room temperature from the CaIrO(3)-type polymorph to another with the U(2)S(3)-type structure. Because alumina is used as window material in shock-wave experiments, this transformation should be important for the analysis of sho...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0711925105

    authors: Umemoto K,Wentzcovitch RM

    更新日期:2008-05-06 00:00:00

  • Pseudouridinylation of mRNA coding sequences alters translation.

    abstract::Chemical modifications of RNAs have long been established as key modulators of nonprotein-coding RNA structure and function in cells. There is a growing appreciation that messenger RNA (mRNA) sequences responsible for directing protein synthesis can also be posttranscriptionally modified. The enzymatic incorporation o...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1821754116

    authors: Eyler DE,Franco MK,Batool Z,Wu MZ,Dubuke ML,Dobosz-Bartoszek M,Jones JD,Polikanov YS,Roy B,Koutmou KS

    更新日期:2019-11-12 00:00:00

  • Targeted ablation of cholinergic interneurons in the dorsolateral striatum produces behavioral manifestations of Tourette syndrome.

    abstract::Gilles de la Tourette syndrome (TS) is characterized by tics, which are transiently worsened by stress, acute administration of dopaminergic drugs, and by subtle deficits in motor coordination and sensorimotor gating. It represents the most severe end of a spectrum of tic disorders that, in aggregate, affect ∼ 5% of t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1419533112

    authors: Xu M,Kobets A,Du JC,Lennington J,Li L,Banasr M,Duman RS,Vaccarino FM,DiLeone RJ,Pittenger C

    更新日期:2015-01-20 00:00:00

  • Mycobacterium tuberculosis glycosylated phosphatidylinositol causes phagosome maturation arrest.

    abstract::The tubercle bacillus parasitizes macrophages by inhibiting phagosome maturation into the phagolysosome. This phenomenon underlies the tuberculosis pandemic involving 2 billion people. We report here how Mycobacterium tuberculosis causes phagosome maturation arrest. A glycosylated M. tuberculosis phosphatidylinositol ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0737613100

    authors: Fratti RA,Chua J,Vergne I,Deretic V

    更新日期:2003-04-29 00:00:00

  • Transcriptional repression specifies the central cell for double fertilization.

    abstract::Double fertilization is a key innovation for the evolutionary success of angiosperms by which the two fertilized female gametes, the egg cell and central cell, generate the embryo and endosperm, respectively. The female gametophyte (embryo sac) enclosed in the sporophyte is derived from a one-celled haploid cell linea...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1909465117

    authors: Zhang MX,Zhu SS,Xu YC,Guo YL,Yang WC,Li HJ

    更新日期:2020-03-17 00:00:00

  • An approach to the multiple-minima problem by relaxing dimensionality.

    abstract::A method is presented for starting from a very-low-energy high-dimensional conformation and obtaining a low-energy three-dimensional structure by gradual contraction of the dimensionality. The contraction in dimensionality is achieved by use of Cayley-Menger determinants, of which a simplified form is derived here. Pr...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.83.9.2782

    authors: Purisima EO,Scheraga HA

    更新日期:1986-05-01 00:00:00

  • An experimental test for lineage-specific position effects on alcohol dehydrogenase (Adh) genes in Drosophila.

    abstract::Independent transgene insertions differ in expression based on their location in the genome; these position effects are of interest because they reflect the influence of genome organization on gene regulation. Position effects also represent potentially insurmountable obstacles to the rigorous functional comparison of...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.26.15513

    authors: Siegal ML,Hartl DL

    更新日期:1998-12-22 00:00:00

  • Nonmuscle myosin II powered transport of newly formed collagen fibrils at the plasma membrane.

    abstract::Collagen fibrils can exceed thousands of microns in length and are therefore the longest, largest, and most size-pleomorphic protein polymers in vertebrates; thus, knowing how cells transport collagen fibrils is essential for a more complete understanding of protein transport and its role in tissue morphogenesis. Here...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1314348110

    authors: Kalson NS,Starborg T,Lu Y,Mironov A,Humphries SM,Holmes DF,Kadler KE

    更新日期:2013-12-03 00:00:00

  • Inhibition of growth of pancreatic carcinomas in animal models by analogs of hypothalamic hormones.

    abstract::Using animal models of acinar and ductal pancreatic cancer, we investigated the effect of analogs of hypothalamic hormones on tumor growth. In Wistar/Lewis rats bearing the acinar pancreatic tumor DNCP-322, chronic administration of [L-5-Br-Trp8]somatostatin-14 significantly decreased tumor weights and volume. Somatos...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.81.1.248

    authors: Redding TW,Schally AV

    更新日期:1984-01-01 00:00:00

  • Genetic elimination of dengue vector mosquitoes.

    abstract::An approach based on mosquitoes carrying a conditional dominant lethal gene (release of insects carrying a dominant lethal, RIDL) is being developed to control the transmission of dengue viruses by vector population suppression. A transgenic strain, designated OX3604C, of the major dengue vector, Aedes aegypti, was en...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1019295108

    authors: Wise de Valdez MR,Nimmo D,Betz J,Gong HF,James AA,Alphey L,Black WC 4th

    更新日期:2011-03-22 00:00:00

  • Nuclear structure in normal and Bloom syndrome cells.

    abstract::Bloom syndrome (BS) is a rare cancer-predisposing disorder in which the cells of affected persons have a high frequency of somatic mutation and genomic instability. BLM, the protein altered in BS, is a RecQ DNA helicase. This report shows that BLM is found in the nucleus of normal human cells in the nuclear domain 10 ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.090525897

    authors: Yankiwski V,Marciniak RA,Guarente L,Neff NF

    更新日期:2000-05-09 00:00:00

  • Structure of CrgA, a cell division structural and regulatory protein from Mycobacterium tuberculosis, in lipid bilayers.

    abstract::The 93-residue transmembrane protein CrgA in Mycobacterium tuberculosis is a central component of the divisome, a large macromolecular machine responsible for cell division. Through interactions with multiple other components including FtsZ, FtsQ, FtsI (PBPB), PBPA, and CwsA, CrgA facilitates the recruitment of the pr...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1415908112

    authors: Das N,Dai J,Hung I,Rajagopalan MR,Zhou HX,Cross TA

    更新日期:2015-01-13 00:00:00

  • In situ growth of a PEG-like polymer from the C terminus of an intein fusion protein improves pharmacokinetics and tumor accumulation.

    abstract::This paper reports a general in situ method to grow a polymer conjugate solely from the C terminus of a recombinant protein. GFP was fused at its C terminus with an intein; cleavage of the intein provided a unique thioester moiety at the C terminus of GFP that was used to install an atom transfer radical polymerizatio...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1006044107

    authors: Gao W,Liu W,Christensen T,Zalutsky MR,Chilkoti A

    更新日期:2010-09-21 00:00:00

  • Placental-specific insulin-like growth factor 2 (Igf2) regulates the diffusional exchange characteristics of the mouse placenta.

    abstract::Restricted fetal growth is associated with postnatal mortality and morbidity and may be directly related to alterations in the capacity of the placenta to supply nutrients. We proposed previously that imprinted genes can regulate nutrient supply by the placenta. Here, we tested the hypothesis that the insulin-like gro...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0402508101

    authors: Sibley CP,Coan PM,Ferguson-Smith AC,Dean W,Hughes J,Smith P,Reik W,Burton GJ,Fowden AL,Constância M

    更新日期:2004-05-25 00:00:00

  • Transdominant genetic analysis of a growth control pathway.

    abstract::Genetic selections that use proteinaceous transdominant inhibitors encoded by DNA libraries to cause mutant phenocopies may facilitate genetic analysis in traditionally nongenetic organisms. We performed a selection for random short peptides and larger protein fragments (collectively termed "perturbagens") that inhibi...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.13.7508

    authors: Caponigro G,Abedi MR,Hurlburt AP,Maxfield A,Judd W,Kamb A

    更新日期:1998-06-23 00:00:00

  • Locus on human X chromosome for dihydrotestosterone receptor and androgen insensitivity.

    abstract::We have studied androgen binding characteristics of cells for androgen insensitivity from an obligate heterozygote, who is the mother of three male pseudohermaphrodites with dihydrotestosterone (17beta-hydroxy-5alpha-androstan-3-one) receptor deficiency. Specific dihydrotestosterone binding by skin fibroblasts from he...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.72.4.1469

    authors: Meyer WJ 3rd,Migeon BR,Migeon CJ

    更新日期:1975-04-01 00:00:00

  • Fibroblast growth factor signaling instructs ensheathing glia wrapping of Drosophila olfactory glomeruli.

    abstract::The formation of complex but highly organized neural circuits requires interactions between neurons and glia. During the assembly of the Drosophila olfactory circuit, 50 olfactory receptor neuron (ORN) classes and 50 projection neuron (PN) classes form synaptic connections in 50 glomerular compartments in the antennal...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1706533114

    authors: Wu B,Li J,Chou YH,Luginbuhl D,Luo L

    更新日期:2017-07-18 00:00:00

  • Calcium/calmodulin-dependent kinase II and long-term potentiation enhance synaptic transmission by the same mechanism.

    abstract::Ca(2+)-sensitive kinases are thought to play a role in long-term potentiation (LTP). To test the involvement of Ca2+/calmodulin-dependent kinase II (CaM-K II), truncated, constitutively active form of this kinase was directly injected into CA1 hippocampal pyramidal cells. Inclusion of CaM-K II in the recording pipette...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.92.24.11175

    authors: Lledo PM,Hjelmstad GO,Mukherji S,Soderling TR,Malenka RC,Nicoll RA

    更新日期:1995-11-21 00:00:00

  • Cell line-specific differences in the control of cell cycle progression in the absence of mitosis.

    abstract::This paper reports that there are major differences between mammalian cell lines in the propensity to progress into subsequent cell cycles when mitosis is inhibited with agents that disrupt the assembly of the mitotic spindle apparatus (Colcemid, nocodazole, and taxol). Human HeLa S3 cells, which represent one extreme...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.24.9553

    authors: Kung AL,Sherwood SW,Schimke RT

    更新日期:1990-12-01 00:00:00

  • An invariant aspartic acid in the DNA glycosylase domain of DEMETER is necessary for transcriptional activation of the imprinted MEDEA gene.

    abstract::Helix-hairpin-helix DNA glycosylases are typically small proteins that initiate repair of DNA by excising damaged or mispaired bases. An invariant aspartic acid in the active site is involved in catalyzing the excision reaction. Replacement of this critical residue with an asparagine severely reduces catalytic activit...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0402328101

    authors: Choi Y,Harada JJ,Goldberg RB,Fischer RL

    更新日期:2004-05-11 00:00:00