ライフサイエンスコーパス: cGAMP

1 cGAMP activates stimulator of interferon genes (STING),

2 cGAMP activates STING which triggers innate immune respo

3 cGAMP alone enhances expression of inflammasome componen

4 cGAMP enhances innate immune responses by inducing produ

5 cGAMP functions as a second messenger that binds to and

6 cGAMP induced LC3 lipidation through a pathway that is d

7 cGAMP is generated from GTP and ATP by cytoplasmic dsDNA

8 cGAMP treatment activated dendritic cells and enhanced c

9 cGAMP-PC7A NP requires endocytosis for intracellular del

10 cGAMP-PC7A NP-induced protection is mediated through typ

11 cGAMP-PC7A NPs also inhibit HIV-1 replication in HIV(+)

12 ct stimulation of pDCs by STING agonist 2'3' cGAMP or dsDNA, pDC-s produced type I, and type III IFN.

13 ess, anemone STING binds mixed-linkage 2',3' cGAMP indistinguishably from human STING, trapping a uni

14 thus the evolutionary origins of human 2',3' cGAMP signaling are unknown.

15 gnals in response to cytosolic DNA via 2',3' cGAMP, a cyclic dinucleotide (CDN) second messenger cont

16 2'3'-cGAMP acts as a second messenger for STING activation an

17 Streptococcus pneumoniae infection than 2'3'-cGAMP adjuvanted vaccine.

18 genomes and define a prominent role for 2'3'-cGAMP cleavage in metazoan host-pathogen conflict.

19 vely active in the absence of exogenous 2'3'-cGAMP in vitro.

20 port that the metazoan second messenger 2'3'-cGAMP induces closing of the human STING homodimer and r

21 Exogenous 2'3'-cGAMP produced by malignant cells(9) and other CDNs, inc

22 Our data suggest widespread 2'3'-cGAMP signaling in insect antiviral immunity and explain

23 er, and acts as a partial antagonist of 2'3'-cGAMP signaling.

24 hat degrade the immune second messenger 2'3'-cGAMP to inhibit cGAS-STING immunity in mammalian cells.

25 ential binding of the asymmetric ligand 2'3'-cGAMP to the symmetric dimer of STING represents a physi

26 ation of mixed phosphodiester linkages (2'3'-cGAMP) is an endogenous second messenger molecule that a

27 monophosphate-adenosine monophosphate (2'3'-cGAMP) is the endogenous ligand for STING, but is rapidl

28 monophosphate-adenosine monophosphate (2'3'-cGAMP)(4-7).

29 s upon treatment with 2'3'-cyclic GAMP (2'3'-cGAMP), the natural agonist of STING (i.e., stimulator o

30 thioate linkages, are more potent than 2',3'-cGAMP (EC50 of 19.6 muM).

31 triggered by ligands of STING such as 2',3'-cGAMP and also activated IFN-beta and ISG expression; an

32 cellular nucleases are known to cleave 2',3'-cGAMP and prevent the activation of the receptor stimula

33 Here we show that 2'3'-cGAMP, but not its linkage isomers, adopts an organized

34 The cyclic dinucleotide 2',3'-cGAMP can bind the adaptor protein STING (stimulator of

35 host poxin homologues retain selective 2',3'-cGAMP degradation activity, suggesting an ancient role f

36 ates define the mechanism of selective 2',3'-cGAMP degradation through metal-independent cleavage of

37 cleavage of the 3'-5' bond, converting 2',3'-cGAMP into linear Gp[2'-5']Ap[3'].

38 2',3'-cGAMP is a potent inducer of immune signalling; however,

39 This molecule, termed 2'3'-cGAMP, is unique in that it binds to the adaptor protein

40 cAIMP analogs are more resistant than 2',3'-cGAMP to enzymatic cleavage in vitro.

41 Poxins cleave 2',3'-cGAMP to restrict STING-dependent signalling and deletio

42 ctively compared with either ssRNA40 or 2'3'-cGAMP, which activate other pattern recognition receptor

43 Activated cGAS synthesizes 2'3'-cGAMP, which we subsequently can detect using liquid chr

44 agonists for murine (DMXAA) or human (2',3'-cGAMP) STING.

45 h the noncanonical cyclic dinucleotide 2',3'-cGAMP, suggesting that the STING pathway may be compromi

46 mune nucleases (poxins) as a family of 2',3'-cGAMP-degrading enzymes.

47 r results define poxins as a family of 2',3'-cGAMP-specific nucleases and demonstrate a mechanism for

48 also inhibited the priming efficacy of 2'3'-cGAMP.

49 MP-AMP (3'3'-cGAMP) but not c-di-GMP or 2'3'-cGAMP.

50 tivity of the potent STING agonist, CDN 3'3'-cGAMP (cGAMP), encapsulated in acid-sensitive acetalated

51 eukemia, injection of the STING agonist 3'3'-cGAMP induced apoptosis and tumor regression.

52 ly efficacious effects were elicited by 3'3'-cGAMP injection in syngeneic or immunodeficient mice gra

53 and with lower affinity cyclic GMP-AMP (3'3'-cGAMP) but not c-di-GMP or 2'3'-cGAMP.

54 aling molecule cyclic AMP-GMP (cAG or 3', 3'-cGAMP).

55 specifically regulates cyclic GMP-AMP (3',3'-cGAMP) levels in vivo to stimulate gene expression assoc

56 onally, treatment with the STING ligand, 2,3-cGAMP, inhibited C. rodentium-induced colitis in vivo.

57 cture of mouse cGAS bound to dsDNA and 2',5' cGAMP provided insight into the catalytic mechanism of c

58 of a noncanonical cyclic dinucleotide, 2',5' cGAMP, that binds to STING and mediates the activation o

59 the unique ability of cGAS to produce 2'-5' cGAMP.

60 MP-GMP (cAG, also referenced as 3'-5', 3'-5' cGAMP) called DncV is associated with hyperinfectivity o

61 the human cGAS active site to produce 3'-5' cGAMP, leading to selective stimulation of alternative S

62 We previously identified SLC19A1 as a cGAMP importer, but its use across human cell lines is l

63 ntitative mass spectrometry, we identified a cGAMP synthase (cGAS), which belongs to the nucleotidylt

64 , we reveal that the HD-GYP enzyme PmxA is a cGAMP-specific phosphodiesterase (GAP) that promotes res

65 Abolishing cGAMP production in Cgas(-/-) tumor cells, depletion of

66 We report that the STING activator cGAMP possesses significant antitumor activity in mice b

67 osphorylation in hepatocytes and adipocytes, cGAMP weakens the effects of glucagon on stimulating hep

68 is essential for induction of IFNbeta after cGAMP stimulation.

69 uction, and STING agonists such as cGMP-AMP (cGAMP) and other cyclic dinucleotides elicit potent immu

70 2',5'/3',5'-cGMP-AMP (cGAMP) is a second messenger produced in response to cyt

71 cGMP-AMP (cGAMP) synthase (cGAS) is a cytosolic DNA sensor that ac

72 t produces the cyclic dinucleotide cGMP-AMP (cGAMP) upon activation, which binds to and activates sti

73 and catalyzes the formation of 2'3'cGMP-AMP (cGAMP), which in turn triggers interferon (IFN) producti

74 Cyclic-G/AMP (cGAMP) synthase (cGAS) triggers host innate immune respo

75 Endogenous cyclic GMP-AMP (cGAMP) binds and activates STING to induce type I interf

76 to catalyse the synthesis of cyclic GMP-AMP (cGAMP) from GTP and ATP(3).

77 2'3'-cyclic-GMP-AMP (cGAMP) is a second messenger that activates the antivira

78 Extracellular 2'3'-cyclic-GMP-AMP (cGAMP) is an immunotransmitter exported by diseased cell

79 3',3'-cyclic GMP-AMP (cGAMP) is the third cyclic dinucleotide (CDN) to be disc

80 on, which is induced by 2'3' cyclic GMP-AMP (cGAMP) produced by the cGAMP synthase in response to cyt

81 rs including the DNA sensors cyclic GMP-AMP (cGAMP) synthase (cGAS) and interferon gamma (IFNgamma)-i

82 A-sensing pathway comprising cyclic GMP-AMP (cGAMP) synthase (cGAS) and stimulator of IFN gene (STING

83 Cyclic GMP-AMP (cGAMP) synthase (cGAS) detects infections or tissue dama

84 Cyclic GMP-AMP (cGAMP) synthase (cGAS) is a cytosolic DNA sensor that ac

85 Cyclic GMP-AMP (cGAMP) synthase (cGAS) is a cytosolic DNA sensor that ac

86 Cyclic GMP-AMP (cGAMP) synthase (cGAS) is a major responder to the patho

87 Cyclic GMP-AMP (cGAMP) synthase (cGAS) is recently identified as a cytos

88 Here, we show that cyclic-di-GMP-AMP (cGAMP) synthase (cGAS) is the primary sensor that mediat

89 The cytosolic DNA sensor cyclic GMP-AMP (cGAMP) synthase (cGAS) mediated sensing of irradiated-tu

90 been well demonstrated that cyclic GMP-AMP (cGAMP) synthase (cGAS) plays an important role in sensin

91 Binding of dsDNA by cyclic GMP-AMP (cGAMP) synthase (cGAS) triggers formation of the metazoa

92 osolic nucleic acid receptor cyclic GMP-AMP (cGAMP) synthase (cGAS), but cGAS nevertheless contribute

93 e host cytosolic DNA sensor, cyclic GMP-AMP (cGAMP) synthase (cGAS), resulting in production of the s

94 l detected by the DNA sensor cyclic-GMP-AMP (cGAMP) synthase (cGAS), which catalyzes the production o

95 NA, the cytosolic DNA sensor cyclic GMP-AMP (cGAMP) synthetase (cGAS) produces the second messenger c

96 ynthase, which produces 2'3'-cyclic GMP-AMP (cGAMP) that binds to and activates stimulator of interfe

97 otide second messenger 2',3'-cyclic GMP-AMP (cGAMP)(1-4).

98 t catalyses the synthesis of cyclic GMP-AMP (cGAMP)(9-12), which stimulates the induction of type I i

99 nses than the mammalian 2'3'-cyclic GMP-AMP (cGAMP), and generated better protection against Streptoc

100 al injection of cyclic dinucleotide GMP-AMP (cGAMP), potently enhanced antitumor CD8 T responses lead

101 hesis of a second messenger, cyclic GMP-AMP (cGAMP), which activates stimulator of interferon genes (

102 ion of the second messenger, cyclic GMP-AMP (cGAMP), which binds and activates stimulator of interfer

103 cGAS synthesizes cyclic GMP-AMP (cGAMP), which binds to the adaptor STIMULATOR OF INTERFE

104 the inhibition of the 2',3'-cyclic GMP-AMP (cGAMP)-dependent immune responses during infection.

105 ly lysophosphatidic acid and cyclic GMP-AMP (cGAMP).

106 or the natural STING ligand cyclic GMP-AMP (cGAMP).

107 roduces the second messenger cyclic GMP-AMP (cGAMP).

108 osphate (GMP)-adenosine monophosphate (AMP) (cGAMP) synthase (cGAS), which produces the second messen

109 ng lipid A, LPS, poly(I:C), poly(dA:dT), and cGAMP, induce cGAS expression in an IFN-I-dependent mann

110 itive liposomes co-encapsulating CpG ODN and cGAMP induced synergistic innate immune response by elev

111 ric state (about 80 kDa in size), as well as cGAMP-bound chicken STING in both the dimeric and tetram

112 Upon binding cGAMP, STING translocates to the endoplasmic reticulum-G

113 ull-length STING oligomerizes after it binds cGAMP, and highlight this as an essential step in the ac

114 s innate immune responses by regulating both cGAMP production and autophagy, resulting in well-balanc

115 two signals, both of which are activated by cGAMP.

116 The vigorous immune responses elicited by cGAMP with no overt skin irritation was attributable to

117 ure of the ligand-binding domain, induced by cGAMP, leads to a 180 degrees rotation of the ligand-bin

118 ligomerization of STING and TBK1, induced by cGAMP, leads to STING phosphorylation by TBK1.

119 tion in human macrophages from inhibition by cGAMP, the product of activated cGAS.

120 g liquid-phase condensation, as monitored by cGAMP formation, gel shift, spin-down, and turbidity ass

121 induced by membrane fusion or IAV but not by cGAMP or DNA.

122 for the downstream signalling stimulated by cGAMP, facilitating recruitment and activation of TANK-b

123 ot interferons in response to stimulation by cGAMP, which suggests that induction of autophagy is a p

124 echanisms that govern activation of STING by cGAMP and subsequent activation of TBK1 by STING remain

125 Innate immune responses triggered by cGAMP contribute to limiting the spread of DENV to adjac

126 okaryotic dinucleotide cyclase for canonical cGAMP share conserved secondary structures and catalytic

127 lic DNA sensor and generates a non-canonical cGAMP that contains G(2',5')pA and A(3',5')pG phosphodie

128 bound to DNA in the cytoplasm and catalyzed cGAMP synthesis.

129 of the potent STING agonist, CDN 3'3'-cGAMP (cGAMP), encapsulated in acid-sensitive acetalated dextra

130 The cyclic GMP-AMP synthase (cGAS)-cGAMP-STING pathway plays a key role in innate immunity,

131 of DNA sensing by the newly discovered cGAS-cGAMP-STING pathway and highlight recent progress in dis

132 The newly discovered DNA-sensing cGAS-cGAMP-STING pathway mediates type I interferon inflammat

133 t, tissue-specific or integrated in the cGAS-cGAMP pathway is unclear.

134 s demonstrated an expanding role of the cGAS-cGAMP-STING pathway in many physiological and pathologic

135 ed, suggesting an important role of the cGAS-cGAMP-STING pathway in the networking and coordination o

136 Potential interactions of the cGAS-cGAMP-STING pathway with mTORC1 signaling, autophagy, an

137 everse-transcribed and detected via the cGAS-cGAMP-STING pathway, triggering a second, sustained wave

138 action, and tissue-specific role of the cGAS-cGAMP-STING signaling pathway in metabolic disorders rem

139 The cGAS-cGAMP-STING-IRF3 pathway of cytosolic DNA sensing plays

140 In mice, cGAS/cGAMP amplify both inflammasome and IFN-I to control mur

141 These mutations confer cGAMP-independent constitutive activation of type I inte

142 g hSTING to mSting, 2',5'-linkage-containing cGAMP isomers were more specific triggers of the IFN pat

143 that involves the transport of tumor-derived cGAMP into macrophages via the ATP-activated channel P2X

144 mportant evidence for potentially developing cGAMP or other STING agonists as a new class of immune-s

145 Compared to soluble cGAMP, the Ace-DEX cGAMP MPs enhanced type-I interferon responses nearly 10

146 The cyclic dinucleotide cGAMP was found to potently inhibit the replication of H

147 ular dsDNA producing the cyclic dinucleotide cGAMP, a second messenger initiating cytokine production

148 S) and generation of the cyclic dinucleotide cGAMP, followed by the induction of stimulator of interf

149 es the production of the cyclic dinucleotide cGAMP, resulting in type I interferon responses.

150 duces a cyclic guanine-adenine dinucleotide (cGAMP) inducer of STING, has been examined to determine

151 AS synthesizes a unique cyclic dinucleotide (cGAMP) containing a 2'-5' phosphodiester linkage essenti

152 AG)) and the other to a cyclic dinucleotide (cGAMP), are solved using NMR spectroscopy.

153 For these reasons, Ace-DEX MP-encapsulated cGAMP represents a potent vaccine adjuvant of humoral an

154 ation improves the half-life of encapsulated cGAMP by 40-fold, allowing for sufficient accumulation o

155 Furthermore, the encapsulated cGAMP elicited no observable toxicity in animals and ach

156 unique phosphodiester linkages in endogenous cGAMP that distinguish it from microbial cGAMP and other

157 Here we show that endogenous cGAMP in mammalian cells contains two distinct phosphodi

158 - a polymersome platform designed to enhance cGAMP delivery - we investigate the pharmacokinetic (PK)

159 Here we show that exogenous cGAMP ameliorates obesity-associated metabolic dysregula

160 d anion channels (VRAC), as widely expressed cGAMP transporters.

161 ies that advance insights into extracellular cGAMP levels in healthy and diseased tissues, such as ca

162 7R to enhance the transport of extracellular cGAMP into macrophages and subsequent STING activation.

163 The enhancement of extracellular cGAMP levels therefore holds great promise for managing

164 n identified, and the signaling pathways for cGAMP have been inferred to display a narrow distributio

165 we show that TMEM203 protein is required for cGAMP-induced STING activation.

166 We recently identified a novel role for cGAMP as a soluble, extracellular immunotransmitter that

167 these results suggest an essential role for cGAMP in linking innate immunity and metabolic homeostas

168 nson et al. report an unanticipated role for cGAMP in priming and activation of inflammasomes in addi

169 Furthermore, cGAMP improved the antitumor activity of 5-FU, and clear

170 nt host response to cytosolic DNA, c-di-GMP, cGAMP, HIV-1, and DNA viruses.

171 However, how cGAMP-bound STING activates TBK1 and IRF3 is not underst

172 However, it is unknown how cGAMP and other CDNs cross the cell membrane to activate

173 e we illuminate the ancient origins of human cGAMP signaling by discovery of a functional cGAS-STING

174 human vasculature cells and universal human cGAMP transporters when activated.

175 Depletion of IFI16 in macrophages impairs cGAMP production on DNA stimulation, whereas overexpress

176 distribution profile, resulting in increased cGAMP accumulation and STING activation in the liver and

177 In contrast, LRRC8D inhibits cGAMP transport.

178 ed to the injection site before the injected cGAMP was diffused out.

179 These discoveries will provide insight into cGAMP's role as an immunotransmitter and aid in the deve

180 he production of dsDNA-induced intracellular cGAMP is suppressed in a dose-dependent manner.

181 ponse to extracellular but not intracellular cGAMP.

182 in growing tumors or induced by intratumoral cGAMP injection was dependent on type I IFNs produced in

183 nd trafficking through a mechanism involving cGAMP.

184 Finally, LRRC8A channels are key cGAMP transporters in resting primary human vasculature

185 ctivated by RNA, Toll-like receptor ligands, cGAMP, or recombinant interferon.

186 hese results reveal that human mixed-linkage cGAMP achieves universal signaling by exploiting a deepl

187 hemical tools to manipulate channel-mediated cGAMP transport.

188 y, activation of STING by a second messenger cGAMP administration enhanced antitumor immunity induced

189 e cyclic dinucleotide (CDN) second messenger cGAMP to activate the signaling adaptor STING.

190 se channels to transfer the second messenger cGAMP to astrocytes, activating the STING pathway and pr

191 thetase (cGAS) produces the second messenger cGAMP to initiate the stimulator of interferon genes (ST

192 ally active to generate the second messenger cGAMP, leading to activation of inflammatory genes, type

193 s through production of the second messenger cGAMP, which activates the adaptor STING.

194 ulting in production of the second messenger cGAMP, which directs the adaptor protein STING to stimul

195 nsor cGAS and generated the second messenger cGAMP, which suppressed endothelial cell proliferation b

196 nterferons by producing the second messenger cGAMP.

197 (cGAS), which produces the second messenger cGAMP.

198 nd host DNA and generates a second-messenger cGAMP, which in turn binds and activates stimulator of I

199 ous cGAMP that distinguish it from microbial cGAMP and other cyclic dinucleotides.

200 osine monophosphate-adenosine monophosphate (cGAMP) mimetic that induces the same "closed" conformati

201 osine monophosphate-adenosine monophosphate (cGAMP) production in vitro more efficiently.

202 osine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) as a cytosolic DNA sensor that tr

203 osine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) binds to DNA and produces cGAMP,

204 osine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) in macrophages to produce cGAMP,

205 osine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) to produce cGAMP, which binds to

206 osine monophosphate-adenosine monophosphate (cGAMP), an agonist of the interferon gene inducer STING

207 osine monophosphate-adenosine monophosphate (cGAMP), robustly augmented and prolonged the cellular an

208 osine monophosphate-adenosine monophosphate (cGAMP), we stimulated peripheral-blood mononuclear cells

209 osine monophosphate-adenosine monophosphate (cGAMP).

210 NP-cGAMP designed for enhanced cytosolic release of cGAMP s

211 umor-bearing lung synergizes with inhaled NP-cGAMP, eliciting systemic anticancer immunity, controlli

212 ne monophosphate-adenosine monophosphate (NP-cGAMP) in mouse models of lung metastases enables rapid

213 metastases enables rapid distribution of NP-cGAMP to both lungs and subsequent uptake by APCs withou

214 The ability of cGAMP to trigger antitumor immunity was further enhanced

215 old, allowing for sufficient accumulation of cGAMP in tumors and activation of the STING pathway in t

216 No activators of cGAMP signaling have yet been identified, and the signal

217 The addition of cGAMP into 1b/Con1 replicon cells significantly increase

218 hown to allow for systemic administration of cGAMP and other cyclic dinucleotides (CDN), but little i

219 this article, we show that administration of cGAMP, delivered by an ultra-pH-sensitive nanoparticle (

220 stasis, indicating potential applications of cGAMP in treating obesity-associated inflammatory and me

221 STING oligomerizes after binding of cGAMP, leading to the recruitment and activation of the

222 ore to understand about the basic biology of cGAMP before its full therapeutic potential can be reali

223 The combination of cGAMP and PD-L1 antibody exerted stronger antitumor effe

224 specifically accelerates the cyclization of cGAMP.

225 zyme assay that relies on the degradation of cGAMP to AMP by ectonucleotide pyrophosphatase phosphodi

226 Consistently, intramuscular delivery of cGAMP inhibited melanoma growth and prolonged the surviv

227 Here, we describe the development of cGAMP-Luc, a coupled enzyme assay that relies on the deg

228 DNA viruses STING is activated downstream of cGAMP synthase (cGAS) to induce type I interferon.

229 s less sensitive to the inhibitory effect of cGAMP than was that of 1b/Con1 replicon.

230 dramatically reduced the antitumor effect of cGAMP.

231 Due to the antitumoral effects of cGAMP, other CDN-based STING agonists are currently unde

232 of STING enhanced the inhibitory effects of cGAMP.

233 is leads to enhanced therapeutic efficacy of cGAMP, inhibition of tumour growth, increased rates of l

234 ified SLC19A1 as the first known importer of cGAMP and other CDNs, including the investigational new

235 ER exit and to activate STING independent of cGAMP binding.

236 Inhibition of cGAMP hydrolysis augmented the UVB-triggered IFN-I respo

237 The antitumor mechanism of cGAMP was verified by STING and IRF3, which were up-regu

238 The potency of cGAMP for cutaneous vaccination was ascribed to a large

239 STING-NPs increase the biological potency of cGAMP, enhance STING signalling in the tumour microenvir

240 drial DNA (mtDNA) to drive the production of cGAMP by cGAS.

241 se (cGAS), which catalyzes the production of cGAMP that in turn serves as a second messenger to activ

242 P designed for enhanced cytosolic release of cGAMP stimulates STING signaling and type I interferons

243 The superior adjuvant effect and safety of cGAMP were also confirmed in a more clinically relevant

244 on limit of MS, the current gold standard of cGAMP quantitation.

245 cGAS catalyzes the synthesis of cGAMP, which functions as a second messenger that binds

246 AS is activated to catalyze the synthesis of cGAMP, which functions as a second messenger that binds

247 gs suggest that cell-to-cell transmission of cGAMP via LRRC8/VRAC channels is central to effective an

248 under diverse stresses, strongly potentiates cGAMP transport.

249 s a nucleotidyltransferase and could produce cGAMP and other cyclic dinucleotides.

250 P) synthase (cGAS) in macrophages to produce cGAMP, a second messenger that activates the adaptor pro

251 phosphate (cGAMP) synthase (cGAS) to produce cGAMP, which binds to and activates the adaptor protein

252 P) synthase (cGAS) binds to DNA and produces cGAMP, which in turn binds to stimulator of interferon g

253 Upon binding DNA, cGAS produces cGAMP that binds to and activates the adaptor protein ST

254 pe I interferon (IFN) signaling by producing cGAMP to initiate antiviral immunity.

255 NG-mediated method to concentrate and purify cGAMP from any type of biological sample.

256 ns, we must be able to detect and quantitate cGAMP with an assay that is high-throughput, sensitive,

257 Secreted cGAMP is then sensed by host cells, eliciting an antitum

258 from GTP and ATP by cytoplasmic dsDNA sensor cGAMP synthase (cGAS).

259 onally, when combined with a priming signal, cGAMP activates the inflammasome through an AIM2, NLRP3,

260 Compared to soluble cGAMP, the Ace-DEX cGAMP MPs enhanced type-I interferon

261 Strikingly, cGAMP exerts cell-type-specific anti-inflammatory effect

262 clin-1 autophagy protein not only suppresses cGAMP synthesis to halt IFN production upon double-stran

263 Temporally, cGAMP induction of IFN-I precedes inflammasome activatio

264 tein STING with a much greater affinity than cGAMP molecules containing other combinations of phospho

265 nt for intrinsic antitumor immunity and that cGAMP may be used directly for cancer immunotherapy.

266 We conclude that cGAMP-Luc is an economical high-throughput assay that ma

267 We demonstrate that cGAMP is effluxed or influxed via LRRC8 channels, as dic

268 These results demonstrated that cGAMP is a novel antitumor agent and has potential appli

269 We recently discovered that cGAMP is exported by cancer cells and that this extracel

270 uantitative mass spectrometry, we found that cGAMP accumulated in mouse tissues deficient in Trex1 or

271 We found that cGAMP added to the culture medium could suppress the rep

272 We propose that cGAMP-Luc is a powerful tool that may enable discoveries

273 Here we show that cGAMP has a noncanonical function in inflammasome activa

274 We show that cGAMP is incorporated into viral particles, including le

275 Furthermore, we show that cGAMP-induced autophagy is important for the clearance o

276 osolic DNA-sensing pathway and suggests that cGAMP treatment might provide a new strategy to improve

277 luxed via LRRC8 channels, as dictated by the cGAMP electrochemical gradient.

278 2'3' cyclic GMP-AMP (cGAMP) produced by the cGAMP synthase in response to cytosolic DNA.

279 IFI16 is also required for the cGAMP-induced activation of STING, and interacts with ST

280 n in the host and leads to activation of the cGAMP synthase-stimulator of IFN genes (cGAS-STING) path

281 Thus, cGAMP activates the inflammasome in addition to IFN-I, a

282 goes a conformational change upon binding to cGAMP(9,14).

283 helial cells, and exposure of these cells to cGAMP resulted in endothelial activation and apoptosis.

284 amined the contribution of anion channels to cGAMP transfer and anti-viral defense.

285 NS4B was identified to confer resistance to cGAMP.

286 In response to cGAMP injection, both in the mouse melanoma model and an

287 responsible for the decreased sensitivity to cGAMP.

288 Virions transferred cGAMP to newly infected cells and triggered a STING-depe

289 ing on their expression levels, to transport cGAMP and other 2'3'-cyclic dinucleotides.

290 hat LRRC8A/LRRC8E-containing VRACs transport cGAMP and cyclic dinucleotides across the plasma membran

291 These two cGAMP-mediated functions, priming and activation, have d

292 STING and IRF3, which were up-regulated upon cGAMP treatment.

293 luding phyla previously not known to utilize cGAMP signaling.

294 skin and ready for immediate activation when cGAMP was injected.

295 However, whether cGAMP plays any roles in regulating metabolic homeostasi

296 Moreover, infection of dendritic cells with cGAMP-loaded lentiviruses enhanced their activation.

297 copy structure of human TBK1 in complex with cGAMP-bound, full-length chicken STING.

298 On stimulation with cGAMP, fibroblasts from the patients showed increased tr

299 In obese mice, treatment with cGAMP significantly decreases diet-induced proinflammato

300 Loading viral vectors with cGAMP therefore holds promise for vaccine development.