ライフサイエンスコーパス: sting

1 induction of stimulator of interferon genes (STING).

2 nd activates stimulator of interferon genes (STING).

3 ile preserving IFN-independent activities of STING.

4 ng COPII-mediated ER-to-Golgi trafficking of STING.

5 at induces the same "closed" conformation of STING.

6 ed by the induction of type I interferons by STING.

7 at he had anaphylaxis caused by the insect's sting.

8 to the cytoplasmic, ligand-binding domain of STING.

9 ller cytotoxicity was dependent on MyD88 and STING.

10 recognized as the main signaling activity of STING.

11 rt mediated by IFN-independent activities of STING.

12 solution, but only dimers bind and activate STING.

13 ts, as it correlates with protection from re-stings.

14 y unspecified causes (20.7%) and hymenoptera stings (5.6%).

15 -mediated disease due to gain-of-function in STING, a key adaptor of IFN signaling.

16 the adaptor STIMULATOR OF INTERFERON GENES (STING), activating an INTERFERON REGULATORY FACTOR 3 (IR

17 Using STING-activating nanoparticles (STING-NPs) - a polymerso

18 usly (i.v.) administered STING-NPs to induce STING activation and inhibit tumor growth.

19 ng pathway, suggesting that GPX4 facilitates STING activation by maintaining redox homeostasis of lip

20 Erroneous STING activation can exacerbate many autoimmune and infl

21 esulting in increased cGAMP accumulation and STING activation in the liver and spleen, which we ident

22 As a consequence of STING activation in tumors, i.v. administered STING-NPs

23 We report that STING activation induces LC3B lipidation onto single-mem

24 , how the intracellular redox state controls STING activation is unclear.

25 Surprisingly, cGAS-STING activation leads to type I IFN transcription but n

26 also found that pharmacologically inhibiting STING activation partially prevented AAD development.

27 mination of the PK-PD relationship governing STING activation upon systemic delivery using STING-NPs,

28 or cells, suggesting that the major role for STING activation was to produce type I IFN.

29 tathione peroxidase 4 (GPX4) is required for STING activation.

30 s, including stimulator of interferon genes (STING) activation.

31 ial strain, referred to as SYNB1891, targets STING-activation to phagocytic antigen-presenting cells

32 ies of STING in macrophages and T cells, and STING activities in T cells are predominantly IFN indepe

33 Stimulator of interferon genes (STING) acts as a cytoplasmic signaling hub of innate imm

34 ING recycling that may have implications for STING agonism in the clinic.

35 Upon direct stimulation of pDCs by STING agonist 2'3' cGAMP or dsDNA, pDC-s produced type I

36 cyclase gene and releases high levels of the STING agonist bis-(3'-5')-cyclic dimeric adenosine monop

37 Overproduction of the STING agonist c-di-AMP significantly enhanced the protec

38 We now show that MCMV acts as a STING agonist in the tumor.

39 The STING agonist was electrostatically complexed with nanot

40 we found to be readily stimulated by a mouse STING agonist, DMXAA.

41 identified a non-nucleotide, small-molecule STING agonist, termed SR-717, that demonstrates broad in

42 -2, an orally available non-nucleotide human STING agonist.

43 Mechanistically, STING agonists activated STAT3 and promoted glycolysis i

44 r future optimization for nanoparticle-based STING agonists and other immunomodulating nanomedicines.

45 enhance intratumoural immune activation, but STING agonists are associated with high toxicity and deg

46 ings support the development of BCG-vectored STING agonists as a tuberculosis vaccine strategy.

47 Locally delivered STING agonists could help to reduce tumour immunosuppres

48 Cyclic dinucleotide STING agonists may comprise a novel class of vaccine adj

49 STING agonists, both 10-carboxymethyl-9-acridanone (CMA)

50 null TNBC cell lines were hyperresponsive to STING agonists.

51 simultaneous miR-181a mediated inhibition of STING allows cells to bypass interferon mediated cell de

52 associated with increased ubiquitination of STING and elevated phosphorylation of STING, TBK1, and I

53 complex represents a new modulatory axis of STING and innate immune signalling at the ER membrane.

54 to fibroblasts, leading to the activation of STING and IRF3-mediated expression of interferon-beta1 a

55 ngulfed by macrophages in which it activated STING and its target interferon regulatory factor 3, whi

56 ctivity of cGAS (based on the phosphorylated STING and phosphorylated TBK1 levels), and the expressio

57 , we tested for genetic interactions between Sting and Pink1/parkin in Drosophila.

58 STEEP was associated with STING and promoted trafficking from the ER.

59 ivity of EGFR and innate immune functions of STING and suggest new experimental and therapeutic appro

60 that the relative contributions of the cGAS-STING and the TLR3 pathways in the attenuation of viral

61 cells with HSV-1 revealed that both the cGAS-STING and the TLR3 signaling pathways are required for t

62 holesterol enrichment in the ER, ER-resident STING and type I IFN (IFN) activation was repressed duri

63 thase (cGAS)-stimulator of interferon genes (STING) and Toll-like receptor 3 (TLR3) pathways.

64 therapy in a stimulator of interferon genes (STING)- and interferon-dependent fashion.

65 We detected an interaction between COPA and STING, and mutant COPA was associated with an accumulati

66 -null TNBC tumors expressed higher levels of STING, and PTEN-null TNBC cell lines were hyperresponsiv

67 examined expression and activities of cGAS, STING, and PYHINs in human lung epithelial cells.

68 dant, cytosolic surveillance systems such as STING are well positioned to detect pathogenic bacteria.

69 ase (cGAS), and the stimulator of IFN genes (STING) are required for pathogenesis, but specific cells

70 sociated with an accumulation of ER-resident STING at the Golgi.

71 tative biomarker and identifies the miR-181a-STING axis as a promising target for therapeutic exploit

72 recognizes baculoviral DNA and that the cGAS-STING axis is primarily responsible for the attenuation

73 (n = 78), followed by drugs (n = 38), insect stings/bites or animal bites (n = 3) and others (n = 11)

74 th (1) breast pain, (2) bother from itching, stinging/burning, swelling, or hurting of the treated br

75 te (2'3'-cGAMP) is the endogenous ligand for STING, but is rapidly metabolized and poorly membrane pe

76 s such as autophagy also occur downstream of STING, but their relative importance during in vivo infe

77 tient was diagnosed with anaphylaxis after a sting by the ant.

78 horylation of a specific tyrosine residue in STING by the epidermal growth factor receptor (EGFR) is

79 Anaphylaxis following insect stings by this ant has been reported frequently in South

80 We also developed STING-CAP, a STING-mediated method to concentrate and pu

81 o nematocysts, the cnidarian venom-producing stinging capsules.

82 oduction of lipid peroxidation, which led to STING carbonylation at C88 and inhibited its trafficking

83 using structure guided design of the murine STING CDN binding domain, we engineer a Forster resonanc

84 anemones, both detect and capture prey using stinging cells called nematocytes which fire a venom-cov

85 In response to MCC cells with restored STING, cocultured T cells expressing MCPyV-specific T ce

86 Thus, MyD88 and STING contribute to MCMV control in distinct cell types

87 lenges the prevailing view and suggests that STING controls HSV-1 infection through IFN-independent a

88 which is equivalent to Cysteine 148 of human STING, controls interferon production.

89 tivating the stimulator of interferon genes (STING) cytosolic DNA-sensing pathway and downstream inte

90 lso indicate that pDC prestimulation of cGAS-STING dampened the TLR9-mediated IFN production.

91 Our study therefore suggests that STING deficiency contributes to the immune suppressive n

92 s-induced enterocolitis did not recapitulate STING deficiency.

93 of STING in AAD development was evaluated in Sting-deficient (Sting(gt/gt)) mice in a sporadic AAD mo

94 No effect of AdrA wt was seen in STING-deficient animals.

95 mise for the treatment of MCC and many other STING-deficient cancers.

96 mSTING) did not rescue RV-A16 replication in STING-deficient cells.

97 In this study, we found that STING-deficient mice had increased weight loss and rough

98 MCMV infection of tumors in STING-deficient mice resulted in normal recruitment of m

99 For dendritic cells derived from STING-deficient mice, no activation was detected.

100 mal-mediated stimulator of interferon genes (STING) degradation.

101 feron-independent functions of STING mediate STING-dependent antiviral responses in vivo.

102 8-OHG release and thus activates the TMEM173/STING-dependent DNA sensor pathway, which results in mac

103 the cytokines TNF or interleukin-1 increased STING-dependent IFN response to extracellular but not in

104 of mutant COPA and silencing of COPA induced STING-dependent IFN signaling.

105 The discovery of TMEM173/STING-dependent innate immunity has recently provided gu

106 ogrammed cell death 1 ligand 1 (PD-L1), in a STING-dependent manner.

107 ragments, which may either activate the cGAS/STING-dependent pathway or-especially in the case of AT-

108 STing determines the sequence type of traditional 7-gene

109 Because STING directly binds to TRIF, we identified the STING-in

110 pid peroxidation specifically attenuates the STING DNA-sensing pathway, suggesting that GPX4 facilita

111 Bacterial STING domains couple the recognition of cyclic dinucleot

112 al immunity and explain how a family of cGAS-STING evasion enzymes evolved from viral proteases throu

113 t viruses suggesting a key mechanism of cGAS-STING evasion may have evolved outside of mammalian biol

114 se they lacked STING expression, and ectopic STING expression restored a cGAS-dependent DNA response

115 failed to respond to DNA because they lacked STING expression, and ectopic STING expression restored

116 ial cells, deficient in cGAS and in cGAS and STING expression, respectively.

117 of the antiviral response, both dependent on STING expression.

118 eutic approaches for selective regulation of STING functions.

119 determine the structure of a full-length TIR-STING fusion from the Pacific oyster Crassostrea gigas.

120 Interestingly, STING gain-of-function mutants from patients interacted

121 In the sporadic AAD model, Sting(gt/gt) mice showed significant reductions in chall

122 induced by anti-MerTK treatment was lost in Sting(gt/gt) mice, but not in Cgas(-/-) mice.

123 These changes were attenuated in challenged Sting(gt/gt) mice.

124 evelopment was evaluated in Sting-deficient (Sting(gt/gt)) mice in a sporadic AAD model induced by ch

125 ecular mechanisms not only give clues to how STING has evolved to distinguish between self and foreig

126 Here we reveal functional STING homologues encoded within prokaryotic defence isla

127 Consistently, STING(-/-) IECs showed reduced capacity to inhibit bacte

128 second messenger 2'3'-cGAMP to inhibit cGAS-STING immunity in mammalian cells.

129 The role of STING in AAD development was evaluated in Sting-deficien

130 ontrasted anti-viral effects of MyD88 versus STING in distinct cell types that are infected with muri

131 hanistic insights into the roles of cGAS and STING in immunity and diseases revealed by these recent

132 als widespread IFN-independent activities of STING in macrophages and T cells, and STING activities i

133 To reactivate STING in MCC, we developed an application of a human STI

134 There were 23 re-stings in 17 (53%) patients during VIT.

135 Furthermore, triggering of cGAS-STING induced expression of SOCS1 and SOCS3 in pDCs, ind

136 The absence of urticaria/angioedema during sting-induced anaphylaxis is indicative of a severe reac

137 worldwide, and approximately one-quarter of sting-induced reactions are classified as severe.

138 n of STAT3 pathway and glycolysis suppressed STING-induced REG3gamma production in IECs, and abrogate

139 ian cells, cyclic dinucleotide activation of STING induces interferon beta expression to initiate inn

140 interferon response can be suppressed with a STING inhibitor.

141 clic GMP-AMP synthase interferon genes (cGAS-STING) innate immune pathway.

142 axis deaths, the most common cause was venom-stinging insect (51.4%).

143 NG directly binds to TRIF, we identified the STING-interacting domain of TRIF and generated STING-non

144 and activates the host cytosolic DNA sensing STING/interferon I pathway, resulting in enhanced cross-

145 nary events that followed the acquisition of STING into metazoan innate immunity, and determine the s

146 Cytosolic mtDNA activated the cGAS/STING/IRF3 pathway, stimulating inflammatory cytokine ge

147 STING is essential for control of infections and for tum

148 Thus, although STING is indispensable for the antiviral activity of Adr

149 e 365 (S365) in the C-terminal tail (CTT) of STING is phosphorylated, leading to induction of type I

150 how that the innate immune signaling protein STING is required for efficient replication of members o

151 Stimulator of interferon genes (STING) is a receptor in human cells that senses foreign

152 te immune regulator stimulator of IFN genes (STING) is completely silenced in MCCs.

153 Stimulator-of-interferon genes (STING) is vital for sensing cytosolic DNA and initiating

154 ron (IFN), which could be limited by CGAS or STING knockdown, mitochondrial DNA depletion or mitochon

155 VP1-2 associated directly with STING, leading to its deubiquitination.

156 se mouse striatum sequester TOLLIP away from STING, leading to reduced STING protein and dampened imm

157 model antigen ovalbumin along with TLR9 and STING ligands within liposomes, a well-established drug

158 Stimulator of interferon genes (STING) links innate immunity to biological processes ran

159 r mechanistic analogy with the IRF3 adaptors STING, MAVS and TRIF(10,11).

160 sm in aortic degeneration and that targeting STING may prevent sporadic AAD development.

161 Thus, interferon-independent functions of STING mediate STING-dependent antiviral responses in viv

162 Tollip(-/-) also ameliorates STING-mediated autoimmune disease in Trex1(-/-) mice.

163 We found that the tumor induces STING-mediated cell death in T cells to evade immune con

164 REG3gamma production in IECs, and abrogated STING-mediated IEC killing of C. rodentium.

165 Moreover, we documented that cGAS-STING-mediated IFN production is mediated by nuclear tra

166 against HSV-1 infection, despite lacking the STING-mediated IFN response.

167 tifying AdrA as the most potent inducer of a STING-mediated IFN response.

168 c GMP-AMP synthase, and their involvement in STING-mediated immunity have been extensively studied.

169 Bone marrow chimeras revealed STING-mediated MCMV control in hematological cells, simi

170 We also developed STING-CAP, a STING-mediated method to concentrate and purify cGAMP fr

171 ssociated molecular patterns, MyD88(-/-) and STING(-/-) mice had 1,350 and 80 copies of spliced trans

172 In this study, we found that STING(-/-) mice were more susceptible to enteric infecti

173 This STING molecule was efficiently delivered to MCC cells vi

174 ity of STING was species-specific, as murine STING (mSTING) did not rescue RV-A16 replication in STIN

175 MCC, we developed an application of a human STING mutant, STING(S162A/G230I/Q266I), which we found t

176 e role in protecting tolerant cultivars from sting nematode feeding and could be targeted in breeding

177 ed to plant defense have negative impacts on sting nematode population densities.

178 Stinging nettle is an annual plant.

179 reparation of the bread with addition of the stinging nettle leaves and its extract, and bread's comp

180 -divanillyltetrahydrofuran (DVT), present in stinging nettle root extracts and used as a nutraceutica

181 ING-interacting domain of TRIF and generated STING-noninteracting mutants of human and mouse TRIFs.

182 Consequently, STING-NPs increased response rates to alphaPD-L1 antibod

183 TING activation in tumors, i.v. administered STING-NPs reprogram the TME towards a more immunogenic a

184 ability of intravenously (i.v.) administered STING-NPs to induce STING activation and inhibit tumor g

185 Using STING-activating nanoparticles (STING-NPs) - a polymersome platform designed to enhance

186 TING activation upon systemic delivery using STING-NPs, providing insight for future optimization for

187 For many, job loss carries the added sting of losing health insurance.

188 ugh CRISPR/Cas9 technology of genes encoding STING or cGAS in NIH/3T3 murine fibroblasts and the infe

189 Accordingly, loss of STING or cGAS in tumor cells decreases tumor infiltratio

190 When alveolar epithelial cells (AECs) lacked Sting or gap junctions were blocked, PS-GAMP-mediated ad

191 function, the response in mice deficient in STING or its downstream effector molecules was analyzed.

192 n of NRF2 signaling, conditional deletion of STING, or blockade of type I interferon receptor I resto

193 able with ICB alone, was independent of TLR, STING, or IFNAR pathways.

194 sDNA, leading to the activation of the IFI16/STING pathway and the production of type I IFNs.

195 activates STING, yet the in vivo role of the STING pathway during bacterial pathogenesis remains uncl

196 es, one of the most prominent being the cGAS-STING pathway for DNA and the RLR-MAVS pathway for RNA,

197 nstrated an expanding role of the cGAS-cGAMP-STING pathway in many physiological and pathological pro

198 results indicate that activation of the cGAS-STING pathway induces V-ATPase-dependent LC3B lipidation

199 The cGAS-STING pathway is a major mechanism that mammalian cells

200 The STING pathway is an essential innate immune signaling ca

201 Dysregulation of the cGAS-STING pathway is responsible for a broad array of inflam

202 nce has shown that self-DNA release and cGAS-STING pathway over-activation can drive lung disease, ma

203 w rapidly, effectively, and specifically the STING pathway responds to a myriad of threats while gene

204 The cGAS-STING pathway responds to viral, bacterial, and self-DNA

205 Particularly, the cGAS-STING pathway resulted in the more relevant production o

206 Therefore, we propose that the cGAS-STING pathway senses unnatural cell fusion through micro

207 ic DNA in aortic cells and activation of the STING pathway were examined in aortic tissues from patie

208 ate immune signalling, mediated via the cGAS/STING pathway, causing degeneration of dopaminergic neur

209 triggers interferon (IFN) production via the STING pathway.

210 ng innate immune signalling through the cGAS-STING pathway.

211 DNA into the cytoplasm, activating the cGAS-STING pathway.

212 R, it is unknown how dMMR activates the cGAS-STING pathway.

213 acrophages and significant activation of the STING pathway.

214 niversally due to aberrant activation of the STING pathway.

215 anism to counteract the IFN-stimulating cGAS-STING pathway.

216 ion and thus specifically inhibited the cGAS-STING pathway.

217 nto host cells to activate the innate immune STING pathway.

218 e innate immunity cytosolic DNA sensing cGAS-STING pathway.

219 undermine antiviral responses induced by the STING pathway.

220 is sensed, a signal is relayed via the cGAS-STING pathway: this involves the activation of cyclic GM

221 ynthase-stimulator of interferon genes (cGAS-STING) pathway activation, and anti-tumoral immunity is

222 onist of the stimulator of interferon genes (STING) pathway and an agonist of the Toll-like receptor

223 ynthase-stimulator of interferon genes (cGAS-STING) pathway by using two approaches: the genetic edit

224 ation of the stimulator of interferon genes (STING) pathway can enhance intratumoural immune activati

225 by the cGAS-stimulator of interferon genes (STING) pathway in patient-derived fibroblasts.

226 The Stimulator of Interferon Genes (STING) pathway initiates potent immune responses upon re

227 The stimulator of interferon genes (STING) pathway plays an important role in the immune sur

228 synthase (cGAS) and stimulator of IFN genes (STING) pathway to induce type I IFN production.

229 cGAMP synthase-stimulator of IFN genes (cGAS-STING) pathway, independent of bacterial ligands.

230 ctivates the stimulator of interferon genes (STING) pathway.

231 thase (cGAS)-stimulator of interferon genes (STING) pathway.

232 M cell lines, in which both the TLR3 and the STING pathways are operational, were used.

233 s the relative contributions of the TLR3 and STING pathways to the attenuation of HSV-1 replication i

234 To determine whether Sting plays a conserved role in Pink1/parkin related pat

235 This inhibited STING polymerization and activation of downstream signal

236 Our data demonstrate that mammalian STING possesses widespread IFN-independent activities th

237 Overall, STING promotes IEC REG3gamma expression to inhibit enter

238 r TOLLIP away from STING, leading to reduced STING protein and dampened immune signaling.

239 he absence of EGFR-mediated phosphorylation, STING rapidly transits into autophagosomes, and IRF3 act

240 Fatal sting reactions are exceedingly rare, but certain factor

241 nderstanding of the anticancer potential for STING receptor activation is currently limited by metabo

242 eals previously unrecognized cross-talk with STING recycling that may have implications for STING ago

243 e development of novel therapeutics to treat STING-related diseases.

244 STING resides on the endoplasmic reticulum (ER) and traf

245 s reveal a molecular basis for the cnidarian stinging response and highlight general principles by wh

246 FN signaling due to a failure of Golgi-to-ER STING retrieval.

247 eplicons failed to amplify in the absence of STING, revealing it to be required for a step in RNA rep

248 More importantly, DMXAA stimulation of STING(S162A/G230I/Q266I) causes robust cell death in MCC

249 Introducing STING(S162A/G230I/Q266I) expression and stimulating its

250 tes that targeted delivery and activation of STING(S162A/G230I/Q266I) in tumor cells holds great ther

251 oped an application of a human STING mutant, STING(S162A/G230I/Q266I), which we found to be readily s

252 Sting(S365A/S365A) mice protect against HSV-1 infection,

253 how metazoan-specific additions to the core STING scaffold enabled a switch from direct effector fun

254 STING shares no structural homology with other known sig

255 for signaling, but we recently reported that STING signaling also requires TRIF.

256 f the neglected interferon (IFN)-independent STING signaling axis in mice.

257 that chromosomal instability activates cGAS/STING signaling but strongly suppresses invasiveness.

258 Thus, STEEP enables STING signaling by promoting ER exit.

259 ance of cancer and, accordingly, agonists of STING signaling have recently emerged as promising thera

260 This review focuses on cGAS-STING signaling in aging, neurodegeneration, and neuroin

261 sing in tumor-associated macrophages through STING signaling is sufficient to promote antitumor immun

262 a due to atypical activation of the neuronal-STING signaling pathway.

263 activation of cytosolic DNA sensing adaptor STING signaling represent a key mechanism in aortic dege

264 l work that collectively paints a picture of STING signaling with atomic resolution.

265 sequent leak of DNA to the cytosol activated STING signaling, which induced cell death through apopto

266 of linkage specificity beyond mammalian cGAS-STING signaling.

267 Type I interferon (IFN) is a major output of STING signaling; however, disrupting IFN signaling durin

268 cell death in MCCs as well as several other STING-silenced cancers.

269 STING (STimulator of INterferon Genes) mediates protecti

270 ifically, the CGAS (cyclic GMP-AMP synthase)-STING (stimulator of interferon genes) pathway mitigates

271 ivation of the cytosolic DNA sensing adaptor STING (stimulator of interferon genes) play a critical r

272 Pharmacological activation of the STING (stimulator of interferon genes)-controlled innate

273 ), an agonist of the interferon gene inducer STING (stimulator of interferon genes).

274 in C9orf72(-/-) myeloid cells, and blocking STING suppresses hyperactive type I interferon responses

275 ion of STING and elevated phosphorylation of STING, TBK1, and IRF3.

276 induction of type I interferons through the STING-TBK1-IRF3 signalling axis(7-11).

277 replication, nor was the C-terminal tail of STING that mediates IRF3 signaling.

278 In the absence of STING, the intestinal immune response was associated wit

279 ere, we identified TOLLIP as a stabilizer of STING through direct interaction to prevent its degradat

280 Degradation of STING through the autolysosomal pathway is diminished in

281 or receptor (EGFR) is required for directing STING to endosomes, where it interacts with its downstre

282 We developed the algorithm STing to provide turn-key solutions for molecular typing

283 TING, suggesting a role for 2C in recruiting STING to RV-A replication organelles.

284 We compared STing to six of the most widely used programs for genome

285 n of RB1 and stimulator-of-interferon-genes (STING) to propagate cells with a high degree of GI.

286 n in part by stimulator of interferon genes (STING), to unexpectedly directly generate HRD.

287 tion, the endoplasmic reticulum (ER) protein STING translocates to endosomes for induction of interfe

288 tivation on Rab7-S72 phosphorylation limited STING turnover and increased downstream production of IR

289 Our implementation of STing uses an innovative k-mer search strategy that elim

290 Recruitment of VP1-2 to STING was dependent on K150 of STING, which was ubiquiti

291 Palmitoylation of STING was not required for RV-A16 replication, nor was t

292 The host factor activity of STING was species-specific, as murine STING (mSTING) did

293 Genetic knockout of Sting was sufficient to completely prevent neurodegenera

294 pecies as that by which the patient had been stung were collected and finally identified as the Asian

295 of RV-A serotypes was strictly dependent on STING, whereas RV-B serotypes were notably less dependen

296 at redox regulation of Cysteine 147 of mouse STING, which is equivalent to Cysteine 148 of human STIN

297 human bronchial epithelial cells did express STING, which was activated after DNA stimulation and med

298 t of VP1-2 to STING was dependent on K150 of STING, which was ubiquitinated by TRIM32.

299 We hope that the adoption of STing will help to democratize microbial genomics and th

300 athogen that secretes c-di-AMP and activates STING, yet the in vivo role of the STING pathway during