ライフサイエンスコーパス: cGAMP

1 cGAMP activates STING which triggers innate immune respo

2 cGAMP alone enhances expression of inflammasome componen

3 cGAMP bound to STING, leading to the activation of IRF3

4 cGAMP enhances innate immune responses by inducing produ

5 cGAMP is generated from GTP and ATP by cytoplasmic dsDNA

6 cGAMP treatment activated dendritic cells and enhanced c

7 cGAMP-PC7A NP requires endocytosis for intracellular del

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

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

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

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

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

13 2'3'-cGAMP acts as a second messenger for STING activation an

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

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

16 The crystal structure of STING bound to 2'3'-cGAMP revealed the structural basis of this high-affinit

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

46 Recent studies identified cyclic GMP-AMP (cGAMP) as a metazoan second messenger triggering an inte

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

109 nterferons by producing the second messenger cGAMP.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

125 dramatically reduced the antitumor effect of cGAMP.

126 of STING enhanced the inhibitory effects of cGAMP.

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

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

129 tion by cGAS and the catalytic mechanisms of cGAMP generation.

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

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

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

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

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

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

136 -adenosine monophosphate (cyclic GMP-AMP, or cGAMP) in vitro from adenosine triphosphate and guanosin

137 -adenosine monophosphate (cyclic GMP-AMP, or cGAMP), which binds to and activates the adaptor protein

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

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

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

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

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

143 ansferase cGAS, its second-messenger product cGAMP, and the cGAMP sensor STING form the basic mechani

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

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

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

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

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

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

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

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

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

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

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

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

156 We also show that cGAMP is an adjuvant that boosts antigen-specific T cell

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

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

159 its second-messenger product cGAMP, and the cGAMP sensor STING form the basic mechanism of DNA sensi

160 2'3' cyclic GMP-AMP (cGAMP) produced by the cGAMP synthase in response to cytosolic DNA.

161 K) and was elicited by CDNs generated by the cGAMP synthase, cGAS.

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

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

164 Thus, cGAMP functions as an endogenous second messenger in met

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

166 NS4B was identified to confer resistance to cGAMP.

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

168 responsible for the decreased sensitivity to cGAMP.

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

170 infection of mammalian cells also triggered cGAMP production.

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

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

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

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

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

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

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

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