Regulatory T cells facilitate the nuclear accumulation of inducible cAMP early repressor (ICER) and suppress nuclear factor of activated T cell c1 (NFATc1).

Abstract:

:Inducible cAMP early repressor (ICER) is a transcriptional repressor, which, because of alternate promoter use, is generated from the 3' region of the cAMP response modulator (Crem) gene. Its expression and nuclear occurrence are elevated by high cAMP levels in naturally occurring regulatory T cells (nTregs). Using two mouse models, we demonstrate that nTregs control the cellular localization of ICER/CREM, and thereby inhibit IL-2 synthesis in conventional CD4(+) T cells. Ablation of nTregs in depletion of regulatory T-cell (DEREG) mice resulted in cytosolic localization of ICER/CREM and increased IL-2 synthesis upon stimulation. Direct contacts between nTregs and conventional CD4(+) T cells led to nuclear accumulation of ICER/CREM and suppression of IL-2 synthesis on administration of CD28 superagonistic (CD28SA) Ab. In a similar way, nTregs communicated with B cells and induced the cAMP-driven nuclear localization of ICER/CREM. High levels of ICER suppressed the induction of nuclear factor of activated T cell c1 (Nfatc1) gene in T cells whose inducible Nfatc1 P1 promoter bears two highly conserved cAMP-responsive elements to which ICER/CREM can bind. These findings suggest that nTregs suppress T-cell responses by the cAMP-dependent nuclear accumulation of ICER/CREM and inhibition of NFATc1 and IL-2 induction.

authors

Vaeth M,Gogishvili T,Bopp T,Klein M,Berberich-Siebelt F,Gattenloehner S,Avots A,Sparwasser T,Grebe N,Schmitt E,Hünig T,Serfling E,Bodor J

doi

10.1073/pnas.1009463108

subject

Has Abstract

pub_date

2011-02-08 00:00:00

pages

2480-5

issue

6

eissn

0027-8424

issn

1091-6490

pii

1009463108

journal_volume

108

pub_type

杂志文章
  • CCAAT/enhancer binding protein alpha (C/EBP alpha) undifferentiated protein: a developmentally regulated nuclear protein that binds to the C/EBP alpha gene promoter.

    abstract::During differentiation of 3T3-L1 preadipocytes into adipocytes, transcription of the C/EBP alpha (CCA-AT/enhancer binding protein alpha) gene is activated. The promoter of the C/EBP alpha gene contains a bipartite cis element with binding sites for C/EBP alpha undifferentiated protein (CUP) and an Sp1-like GT box bind...

    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.90.15.7312

    authors: Vasseur-Cognet M,Lane MD

    更新日期:1993-08-01 00:00:00

  • Quantifying archaeal community autotrophy in the mesopelagic ocean using natural radiocarbon.

    abstract::An ammonia-oxidizing, carbon-fixing archaeon, Candidatus "Nitrosopumilus maritimus," recently was isolated from a salt-water aquarium, definitively confirming that chemoautotrophy exists among the marine archaea. However, in other incubation studies, pelagic archaea also were capable of using organic carbon. It has re...

    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.0510157103

    authors: Ingalls AE,Shah SR,Hansman RL,Aluwihare LI,Santos GM,Druffel ER,Pearson A

    更新日期:2006-04-25 00:00:00

  • Ipilimumab-dependent cell-mediated cytotoxicity of regulatory T cells ex vivo by nonclassical monocytes in melanoma patients.

    abstract::Enhancing immune responses with immune-modulatory monoclonal antibodies directed to inhibitory immune receptors is a promising modality in cancer therapy. Clinical efficacy has been demonstrated with antibodies blocking inhibitory immune checkpoints such as cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) or PD-1/...

    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.1417320112

    authors: Romano E,Kusio-Kobialka M,Foukas PG,Baumgaertner P,Meyer C,Ballabeni P,Michielin O,Weide B,Romero P,Speiser DE

    更新日期:2015-05-12 00:00:00

  • Probing the open state of cytochrome P450cam with ruthenium-linker substrates.

    abstract::Cytochromes P450 play key roles in drug metabolism and disease by oxidizing a wide variety of natural and xenobiotic compounds. High-resolution crystal structures of P450cam bound to ruthenium sensitizer-linked substrates reveal an open conformation of the enzyme that allows substrates to access the active center via ...

    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.221297998

    authors: Dunn AR,Dmochowski IJ,Bilwes AM,Gray HB,Crane BR

    更新日期:2001-10-23 00:00:00

  • IonStar enables high-precision, low-missing-data proteomics quantification in large biological cohorts.

    abstract::Reproducible quantification of large biological cohorts is critical for clinical/pharmaceutical proteomics yet remains challenging because most prevalent methods suffer from drastically declined commonly quantified proteins and substantially deteriorated quantitative quality as cohort size expands. MS2-based data-inde...

    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.1800541115

    authors: Shen X,Shen S,Li J,Hu Q,Nie L,Tu C,Wang X,Poulsen DJ,Orsburn BC,Wang J,Qu J

    更新日期:2018-05-22 00:00:00

  • Molecular mechanical simulations on double intercalation of 9-amino acridine into d(CGCGCGC) X d(GCGCGCG): analysis of the physical basis for the neighbor-exclusion principle.

    abstract::The neighbor-exclusion principle is one of the most general and interesting rules describing intercalative DNA binding by small molecules. It suggests that such binding can only occur at every other base-pair site, reflecting a very large negative cooperativity in the binding process. We have carried out molecular mec...

    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.84.16.5735

    authors: Rao SN,Kollman PA

    更新日期:1987-08-01 00:00:00

  • Two-dimensional infrared spectra reveal relaxation of the nonnucleoside inhibitor TMC278 complexed with HIV-1 reverse transcriptase.

    abstract::The two nitrile groups at the wings of the nonnucleoside HIV-1 reverse transcriptase (RT) inhibitor TMC278 are both identified in high-sensitivity 2D IR spectroscopy experiments of the HIV-1 RT/TMC278 complex. The vibrational spectra indicate that the two arms of the inhibitor sense quite different environments within...

    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.0709320104

    authors: Fang C,Bauman JD,Das K,Remorino A,Arnold E,Hochstrasser RM

    更新日期:2008-02-05 00:00:00

  • Single cell sequencing reveals low levels of aneuploidy across mammalian tissues.

    abstract::Whole-chromosome copy number alterations, also known as aneuploidy, are associated with adverse consequences in most cells and organisms. However, high frequencies of aneuploidy have been reported to occur naturally in the mammalian liver and brain, fueling speculation that aneuploidy provides a selective advantage in...

    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.1415287111

    authors: Knouse KA,Wu J,Whittaker CA,Amon A

    更新日期:2014-09-16 00:00:00

  • Long-term maintenance of species-specific bacterial microbiota in the basal metazoan Hydra.

    abstract::Epithelia in animals are colonized by complex communities of microbes. Although a topic of long-standing interest, understanding the evolution of the microbial communities and their role in triggering innate immune responses has resisted analysis. Cnidaria are among the simplest animals at the tissue grade of organiza...

    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.0703375104

    authors: Fraune S,Bosch TC

    更新日期:2007-08-07 00:00:00

  • LR16, a compound with potent effects on the oxygen affinity of hemoglobin, on blood cholesterol, and on low density lipoprotein.

    abstract::2-[4-(3,4-Dichlorophenylureido)phenoxy]-2-methylpropionic acid, LR16, combines with two symmetrically related sites in the central cavity of deoxyhemoglobin, 20 A away from the binding site of 2,3-bisphosphoglycerate, and acts as an allosteric effector synergistic with 2,3-bisphosphoglycerate. LR16 (1 mM) raises P50, ...

    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.85.16.6117

    authors: Lalezari I,Rahbar S,Lalezari P,Fermi G,Perutz MF

    更新日期:1988-08-01 00:00:00

  • Flow of information in the light-triggered cyclic nucleotide cascade of vision.

    abstract::Photolyzed rhodopsin catalyzes the exchange of GTP for FDP bound to a protein in retinal rod outer segments. We previously proposed that the GTP complex of this protein regulates the cyclic GMP phosphodiesterase and that it may be the first amplified intermediate in visual excitation [Fung, B. K.-K. & Stryer, L. (1980...

    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.78.1.152

    authors: Fung BK,Hurley JB,Stryer L

    更新日期:1981-01-01 00:00:00

  • Sex chromosome evolution: platypus gene mapping suggests that part of the human X chromosome was originally autosomal.

    abstract::To investigate the evolution of the mammalian sex chromosomes, we have compared the gene content of the X chromosomes in the mammalian groups most distantly related to man (marsupials and monotremes). Previous work established that genes on the long arm of the human X chromosome are conserved on the X chromosomes in a...

    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.88.24.11256

    authors: Watson JM,Spencer JA,Riggs AD,Graves JA

    更新日期:1991-12-15 00:00:00

  • Resources and energetics determined dinosaur maximal size.

    abstract::Some dinosaurs reached masses that were approximately 8 times those of the largest, ecologically equivalent terrestrial mammals. The factors most responsible for setting the maximal body size of vertebrates are resource quality and quantity, as modified by the mobility of the consumer, and the vertebrate's rate of ene...

    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.0904000106

    authors: McNab BK

    更新日期:2009-07-21 00:00:00

  • Ionizing radiation and tritium transmutation both cause formation of 5-hydroxymethyl-2'-deoxyuridine in cellular DNA.

    abstract::HeLa cells grown in the presence of [methyl-3H]thymidine contained large amounts of 5-hydroxymethyl-2'-deoxyuridine (HMdU) in their DNA. When the cells were grown in [6-3H]thymidine and their DNA was labeled to the same specific activity, no HMdU was present. When such [6-3H]thymidine-labeled cells were exposed to inc...

    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.81.2.318

    authors: Teebor GW,Frenkel K,Goldstein MS

    更新日期:1984-01-01 00:00:00

  • X chromosome and autosomal recombination are differentially sensitive to disruptions in SC maintenance.

    abstract::The synaptonemal complex (SC) is a conserved meiotic structure that regulates the repair of double-strand breaks (DSBs) into crossovers or gene conversions. The removal of any central-region SC component, such as the Drosophila melanogaster transverse filament protein C(3)G, causes a complete loss of SC structure and ...

    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.1910840116

    authors: Billmyre KK,Cahoon CK,Heenan GM,Wesley ER,Yu Z,Unruh JR,Takeo S,Hawley RS

    更新日期:2019-10-22 00:00:00

  • Induction of glucose-regulated proteins during anaerobic exposure and of heat-shock proteins after reoxygenation.

    abstract::In this report we examine the effects of chronic anaerobic exposure and subsequent reoxygenation on protein synthesis patterns in Chinese hamster ovary cells. It is observed by two-dimensional gel electrophoresis (isoelectric focusing/NaDodSO4/PAGE) that the transition from an atmospheric environment to an anaerobic s...

    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.81.15.4843

    authors: Sciandra JJ,Subjeck JR,Hughes CS

    更新日期:1984-08-01 00:00:00

  • Ten-Eleven-Translocation 2 (TET2) negatively regulates homeostasis and differentiation of hematopoietic stem cells in mice.

    abstract::The Ten-Eleven-Translocation 2 (TET2) gene encodes a member of TET family enzymes that alters the epigenetic status of DNA by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine (5hmC). Somatic loss-of-function mutations of TET2 are frequently observed in patients with diverse myeloid malignancies, including myelody...

    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.1112317108

    authors: Ko M,Bandukwala HS,An J,Lamperti ED,Thompson EC,Hastie R,Tsangaratou A,Rajewsky K,Koralov SB,Rao A

    更新日期:2011-08-30 00:00:00

  • Mutation of Asp74 of the rat angiotensin II receptor confers changes in antagonist affinities and abolishes G-protein coupling.

    abstract::Aspartic acid in the second transmembrane domain is a highly conserved amino acid among the G protein-coupled receptors and is functionally important for agonist binding and G-protein coupling in beta 2-adrenergic and luteinizing hormone receptors. To determine whether this aspartic acid is also involved in the functi...

    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.90.11.5133

    authors: Bihoreau C,Monnot C,Davies E,Teutsch B,Bernstein KE,Corvol P,Clauser E

    更新日期:1993-06-01 00:00:00

  • Methane transport from the active layer to lakes in the Arctic using Toolik Lake, Alaska, as a case study.

    abstract::Methane emissions in the Arctic are important, and may be contributing to global warming. While methane emission rates from Arctic lakes are well documented, methods are needed to quantify the relative contribution of active layer groundwater to the overall lake methane budget. Here we report measurements of natural 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.1417392112

    authors: Paytan A,Lecher AL,Dimova N,Sparrow KJ,Kodovska FG,Murray J,Tulaczyk S,Kessler JD

    更新日期:2015-03-24 00:00:00

  • Designing a functional type 2 copper center that has nitrite reductase activity within α-helical coiled coils.

    abstract::One of the ultimate objectives of de novo protein design is to realize systems capable of catalyzing redox reactions on substrates. This goal is challenging as redox-active proteins require design considerations for both the reduced and oxidized states of the protein. In this paper, we describe the spectroscopic chara...

    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.1212893110

    authors: Tegoni M,Yu F,Bersellini M,Penner-Hahn JE,Pecoraro VL

    更新日期:2012-12-26 00:00:00

  • CDK8/19 Mediator kinases potentiate induction of transcription by NFκB.

    abstract::The nuclear factor-κB (NFκB) family of transcription factors has been implicated in inflammatory disorders, viral infections, and cancer. Most of the drugs that inhibit NFκB show significant side effects, possibly due to sustained NFκB suppression. Drugs affecting induced, but not basal, NFκB activity may have the pot...

    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.1710467114

    authors: Chen M,Liang J,Ji H,Yang Z,Altilia S,Hu B,Schronce A,McDermott MSJ,Schools GP,Lim CU,Oliver D,Shtutman MS,Lu T,Stark GR,Porter DC,Broude EV,Roninson IB

    更新日期:2017-09-19 00:00:00

  • Local auxin biosynthesis regulation by PLETHORA transcription factors controls phyllotaxis in Arabidopsis.

    abstract::Lateral organ distribution at the shoot apical meristem defines specific and robust phyllotaxis patterns that have intrigued biologists and mathematicians for centuries. In silico studies have revealed that this self-organizing process can be recapitulated by modeling the polar transport of the phytohormone auxin. Phy...

    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.1213497110

    authors: Pinon V,Prasad K,Grigg SP,Sanchez-Perez GF,Scheres B

    更新日期:2013-01-15 00:00:00

  • Myoglobin-mediated oxygen delivery to mitochondria of isolated cardiac myocytes.

    abstract::Myoglobin-mediated oxygen delivery to intracellular mitochondria is demonstrated in cardiac myocytes isolated from the hearts of mature rats. Myocytes are held at high ambient oxygen pressure, 40-340 torr (5-45 kPa); sarcoplasmic myoglobin is fully oxygenated. In this condition oxygen availability does not limit respi...

    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.84.21.7503

    authors: Wittenberg BA,Wittenberg JB

    更新日期:1987-11-01 00:00:00

  • Integration of light and abscisic acid signaling during seed germination and early seedling development.

    abstract::Seed germination is regulated by endogenous hormonal cues and external environmental stimuli such as water, low temperature, and light. After germination, the young seedling must rapidly establish its root system and the photoautotrophic capability appropriate to its surrounding environment. Light and the phytohormone...

    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.0710778105

    authors: Chen H,Zhang J,Neff MM,Hong SW,Zhang H,Deng XW,Xiong L

    更新日期:2008-03-18 00:00:00

  • Regulated surface expression and shedding support a dual role for semaphorin 4D in platelet responses to vascular injury.

    abstract::Semaphorin 4D (sema4D; CD100) is an integral membrane protein and the ligand for two receptors, CD72 and plexin-B1. Soluble sema4D has been shown to evoke angiogenic responses from endothelial cells and impair monocyte migration, but the origin of soluble sema4D, particularly at sites of vascular injury, has been uncl...

    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.0606344104

    authors: Zhu L,Bergmeier W,Wu J,Jiang H,Stalker TJ,Cieslak M,Fan R,Boumsell L,Kumanogoh A,Kikutani H,Tamagnone L,Wagner DD,Milla ME,Brass LF

    更新日期:2007-01-30 00:00:00

  • Modulation of rhythmic brain activity by diazepam: GABA(A) receptor subtype and state specificity.

    abstract::The inhibitory neurotransmitter gamma-aminobutyric acid (GABA) is involved in the generation of various brain rhythmic activities that can be modulated by benzodiazepines. Here, we assessed the contribution of alpha(2)GABA type A (GABA(A)) receptors to the effects of benzodiazepines on sleep and waking oscillatory pat...

    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.0306975101

    authors: Kopp C,Rudolph U,Löw K,Tobler I

    更新日期:2004-03-09 00:00:00

  • LDL receptor and its family members serve as the cellular receptors for vesicular stomatitis virus.

    abstract::Vesicular stomatitis virus (VSV) exhibits a remarkably robust and pantropic infectivity, mediated by its coat protein, VSV-G. Using this property, recombinant forms of VSV and VSV-G-pseudotyped viral vectors are being developed for gene therapy, vaccination, and viral oncolysis and are extensively used for gene transd...

    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.1214441110

    authors: Finkelshtein D,Werman A,Novick D,Barak S,Rubinstein M

    更新日期:2013-04-30 00:00:00

  • Decussion geometrics in the goldfish nervous system: correlation with probability of survival.

    abstract::In the goldfish, the optic nerve decussation occurs without intermingling of fibers from the two eyes. In two-thirds of juvenile and adult specimens, the left optic nerve is dorsal at the midline. In about 60% of the specimens, the decussation of Mauthner's neuron also has a left-dorsal-to-right (L/R) configuration. 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.76.8.4131

    authors: Roth RL

    更新日期:1979-08-01 00:00:00

  • Regulation of metallothionein genes by heavy metals appears to be mediated by a zinc-sensitive inhibitor that interacts with a constitutively active transcription factor, MTF-1.

    abstract::A construct, MRE-beta Geo, with five metal response elements fused to a selectable reporter gene was transfected into BHK cells and a stable clone that could be induced up to 100-fold by zinc, cadmium, bismuth, silver, cobalt, copper, mercury, or nickle was isolated. Some, and perhaps all, of these metals induce MRE-b...

    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.91.4.1219

    authors: Palmiter RD

    更新日期:1994-02-15 00:00:00

  • Determination of fructose metabolic pathways in normal and fructose-intolerant children: a 13C NMR study using [U-13C]fructose.

    abstract::An inborn deficiency in the ability of aldolase B to split fructose 1-phosphate is found in humans with hereditary fructose intolerance (HFI). A stable isotope procedure to elucidate the mechanism of conversion of fructose to glucose in normal children and in HFI children has been developed. A constant infusion of 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.87.14.5449

    authors: Gopher A,Vaisman N,Mandel H,Lapidot A

    更新日期:1990-07-01 00:00:00