ライフサイエンスコーパス: eIF2

1 tion factor, eukaryotic initiation factor 2 (eIF2).

2 hosphorylate eukaryotic initiation factor 2 (eIF2).

3 a subunit of eukaryotic initiation factor 2 (eIF2).

4 g with eIF5 for the Met-tRNAi-binding factor eIF2.

5 through a translational mechanism involving eIF2.

6 ects is to control translation by inhibiting eIF2.

7 ion of 5MP with eIF5 for the main substrate, eIF2.

8 g guanine nucleotide exchange on its partner eIF2.

9 release, and changes in the conformation of eIF2.

10 ichiometry and interactions within eIF2B and eIF2.

11 the alpha-subunit of the translation factor eIF2.

12 of eukaryotic translation initiation factor, eIF2.

13 , 5MP1 is not a GEF but a weak GDI for yeast eIF2.

14 e HEAT domain, mediates its interaction with eIF2.

15 2B, a guanine nucleotide exchange factor for eIF2.

16 RNA(Met)(i)) by eukaryotic initiation factor eIF2.

17 ted eukaryotic translation initiation factor eIF2.

18 of the general translation initiation factor eIF2.

19 dies and results in a decreased shuttling of eIF2.

20 phorylation of translation initiation factor eIF2.

21 pha-subunit of translation initiation factor eIF2.

22 IF2S3 gene that encodes the gamma subunit of eIF2.

23 gulation by phosphorylation of the substrate eIF2.

24 trolled by the translation initiation factor eIF2(11).

25 phosphate (CTP) synthase, or subunits of the eIF2/2B translation factor complex.

26 eIF2, a heterotrimeric G-protein, is activated by guanin

27 This reduction in eIF2 activity results in dysregulation of global and gen

28 ssion indicating that Cdc123 is critical for eIF2 activity.

29 eIF2beta mutation does not affect intrinsic eIF2 affinities for these ligands, neither does it inter

30 ylation of the translation initiation factor eIF2 alpha at a conserved serine residue mediates transl

31 (HRI)-eukaryotic initiation factor 2 alpha (eIF2 alpha) kinase is activated in acute heme-deficient

32 To discover compounds that have anti-eIF2α-P activity suitable for clinical use, we per

33 ablishing translation rates by inhibition of eIF2α-P activity, genetically or pharmacologically

34 on this article.Signalling through the PERK/eIF2α-P branch of the unfolded protein response pl

35 ve disease, prolonged overactivation of PERK/eIF2α-P signalling causes sustained attenuation of

36 hloride and dibenzoylmethane, which reversed eIF2α-P-mediated translational attenuation in

37 The upstream UPR constituents pancreatic EIF2-alpha kinase (PERK) and inositol-requiring enzyme 1

38 ion of injury pathways related to persistent eif2-alpha phosphorylation (activating transcription fac

39 with an impaired ability to dephosphorylate eif2-alpha through GADD34, impairing cellular recovery.

40 s observed preferentially in the presence of eIF2(alphaP) and is attenuated by mutations that desensi

41 In vitro, eIF2(alphaP) and ISRIB reciprocally opposed each other's

42 this, beta/Gcd7 can overcome the toxicity of eIF2(alphaP) and rescue native eIF2B function when overe

43 ISRIB and eIF2(alphaP) bind distinct sites in their common target,

44 gement of both eIF2B regulatory sites by two eIF2(alphaP) molecules remodels both the ISRIB-binding p

45 x that mediates tight, inhibitory binding of eIF2(alphaP)-GDP, but the essential functions of delta/G

46 sphorylated translation initiation factor 2, eIF2(alphaP).

47 esensitize eIF2B to the inhibitory effect of eIF2(alphaP).

48 hibitor in cells also depends on presence of eIF2(alphaP).

49 Phosphorylation of eIF2 [eIF2(alphaP)] is critical for translational control in d

50 n a manner inhibited by phosphorylated eIF2 [eIF2(alphaP)].

51 osphorylates eukaryotic initiation factor 2 (eIF2), altering gene-specific translation and initiating

52 ay, glutaryl-CoA/tryptophan degradations and EIF2/AMPK/mTOR signaling.

53 s the guanine nucleotide exchange factor for eIF2 and a critical regulator of protein synthesis, (e.g

54 trate, eIF2-GDP, reaction intermediates, apo-eIF2 and eIF2-GTP, and product, TC, with direct implicat

55 Only minor differences are observed between eIF2 and eIF2alphaP binding to eIF2B, suggesting that th

56 Cross-links between eIF2 and eIF2B allow modelling of interactions that cont

57 Thus, ISRIB targets an interaction between eIF2 and eIF2B that lies at the core of the ISR.

58 Human 5MP1 interacts with eIF2 and eIF3 and inhibits general and gene-specific tra

59 Sel-TCP-seq demonstrated that eIF2 and eIF3 travel along 5' UTRs with scanning 40Ss to

60 eIF4E, and ribosomal protein S6 and studied eIF2 and eIF4F complex.

61 ein termed eIF5-mimic protein (5MP) can bind eIF2 and inhibit general translation.

62 w that eIF5 stabilizes the binding of GDP to eIF2 and is therefore a bi-functional protein that acts

63 l guidance signaling, synaptic transmission, eIF2 and mammalian target of rapamycin (mTOR) signaling

64 eIF1 and a ternary complex (TC) of GTP-bound eIF2 and Met-RNAi scans the mRNA for the start codon.

65 synaptic plasticity, mitochondria function, eIF2 and mTOR signaling and inflammation and provides ne

66 We conclude that eIF2 and p-eIF2 differ in their interaction with eIF2B t

67 Gcn2p phosphorylation of translation factor eIF2 and preferential translation of GCN4, a transcripti

68 sults suggest that 5MP1 interacts with yeast eIF2 and promotes TC formation, but inhibits TC binding

69 inactivate the translation initiation factor eIF2 and stimulate RNA cleavage by RNase L.

70 ghtly linked to the levels of phosphorylated eIF2 and stress damage.

71 e of the platform domain that binds eIF1 and eIF2, and A1193U, changing the h31 loop located below th

72 dentified previously, including eIF1A, eIF1, eIF2, and eIF5.

73 f critical signaling networks, including AR, EIF2, and mTOR/MAPK.

74 Brains from Bdk(-/-) pups exhibited robust eIF2 approximately P and amino acid stress response indu

75 Together these results illustrate how eIF2 approximately P and translational control combined

76 Although eIF2 approximately P elicits translational control in re

77 discordant induction of ATF4 expression and eIF2 approximately P in response to UV irradiation is th

78 tion of eukaryotic initiation factor 2alpha (eIF2 approximately P) by general control nonderepressibl

79 stresses induce the phosphorylation of eIF2 (eIF2 approximately P), repressing global protein synthes

80 not increase ATF4 expression despite robust eIF2 approximately P.

81 not increase ATF4 expression despite robust eIF2 approximately P.

82 of ATF4 and its target genes in response to eIF2 approximately P.

83 ses and their respective stress signals, the eIF2 approximately P/ATF4 pathway is collectively referr

84 Key to controlling the activity of eIF2 are translation factors eIF2B and eIF5, thought to

85 Thus, Cdc123 is a specific eIF2 assembly factor indispensable for the onset of prot

86 f yeast eIF2B in complex with phosphorylated eIF2 at an overall resolution of 4.2 angstrom.

87 of signaling mechanisms, including the GCN2-eIF2-ATF4 pathway.

88 ring asparaginase exposure is not driven via eIF2-ATF4-Sestrin2.

89 ) required for reactivation of the G protein eIF2 between rounds of protein synthesis initiation.

90 hese ligands, neither does it interfere with eIF2 binding to 43S pre-initiation complex components.

91 In protein synthesis translation factor eIF2 binds initiator tRNA to ribosomes and facilitates s

92 ded by a disease risk locus, and, therefore, eIF2 biogenesis control by Cdc123 may prove relevant for

93 control we have determined the structures of eIF2 both in phosphorylated and unphosphorylated forms b

94 eport cryo-electron microscopy structures of eIF2 bound to eIF2B in the dephosphorylated state.

95 eIF5-induced hydrolysis of eIF2-bound GTP is essential for stimulation.

96 Hydrolysis of eIF2-bound GTP is stimulated by eIF5 in the scanning PIC

97 he P site, where it directly base-pairs with eIF2-bound initiator methionyl transfer RNA to form a 48

98 ric eukaryotic translation initiation factor eIF2, cause MEHMO syndrome, an X-linked intellectual dis

99 nus of eIF2gamma impairs CDC123 promotion of eIF2 complex formation and decreases the level of eIF2-G

100 Here we report that assembly of the eIF2 complex in vivo depends on Cdc123, a cell prolifera

101 The elevation of the CUGBP1-eIF2 complex increases translation of C/EBPbeta and HDAC

102 2 complex, nearly comparable to that of eIF5:eIF2 complex produced by eIF5 overexpression.

103 e unassembled eIF2gamma subunit, but not the eIF2 complex, and the C-terminal domain III region of eI

104 uman cells leads to strong formation of 5MP1:eIF2 complex, nearly comparable to that of eIF5:eIF2 com

105 tion, leading to the formation of the CUGBP1-eIF2 complex, which is an activator of translation of CU

106 tors revealed that depletion of conventional eIF2 complexes has adverse effects on normal but not onc

107 in Met-tRNAiMet binding to the mutant yeast eIF2 complexes in vivo and in vitro.

108 of the alpha-subunit of initiation factor 2 (eIF2) controls protein synthesis by a conserved mechanis

109 a phosphorylation and recruitment of NCK1 to eIF2, decreases eIF2alpha phosphorylation and bolsters T

110 Protein synthesis factor eIF2 delivers initiator tRNA to the ribosome.

111 e 40S ribosomal subunit, thereby suppressing eIF2-dependent recognition of the start codon.

112 We conclude that eIF2 and p-eIF2 differ in their interaction with eIF2B to such effe

113 ation factor eIF5 is an important partner of eIF2, directly modulating its function in several critic

114 dly, its GTPase activating function promotes eIF2 dissociation for ribosomal subunit joining.

115 ons, phosphorylation of the alpha-subunit of eIF2 downregulates cellular protein synthesis.

116 PERK phosphorylation of the alpha subunit of eIF2 during ER stress represses protein synthesis, which

117 akes connections to the regulatory domain of eIF2?, eIF1A, and ribosomal elements that allow recognit

118 ental stresses induce the phosphorylation of eIF2 (eIF2 approximately P), repressing global protein s

119 Phosphorylation of eIF2 [eIF2(alphaP)] is critical for translational contro

120 (TC) in a manner inhibited by phosphorylated eIF2 [eIF2(alphaP)].

121 AK3) phosphorylation of the alpha subunit of eIF2 (eIF2alpha approximately P), which represses global

122 subunit of the translation initiation factor eIF2 (eIF2alpha) can promote apoptosis.

123 able of phosphorylating the alpha subunit of eIF2 (eIF2alpha), which sequesters eIF2B to prevent exch

124 ess, phosphorylation of the alpha subunit of eIF2 (eIF2alpha-P) represses global protein synthesis, c

125 the phosphorylation of the alpha subunit of eIF2 (eIF2alpha-P), which represses translation initiati

126 r when TC/eIF5 is formed with phosphorylated eIF2, eIF2B outcompetes eIF5 and destabilizes TC.

127 interaction with eIF2B to such effect that p-eIF2-eIF2B association can be selectively inhibited.

128 the eukaryotic translation initiation factor eIF2-eIF2B complex, reversed the changes in translation

129 re by acting as a competitive inhibitor of p-eIF2-eIF2B interaction.

130 e exchange and initiator tRNA binding to the eIF2/eIF2B complex.

131 in iftb-1, which encodes the beta-subunit of eIF2 (eIF2beta).

132 d eIF2Bgamma subunits and identified a novel eIF2-eIF2Bgamma interaction.

133 e multifactor complex (MFC) comprising eIF1, eIF2, eIF3 and eIF5, similar to the MFC reported in yeas

134 eIF2, eIF3, eIF1 and eIF1A promote efficient 48S initiat

135 The presence of eIF2, eIF3, eIF1, eIF1A, and Met-tRNAi(Met) was sufficie

136 All of them require eIF2, eIF3, eIF4A, eIF4G, eIF4B, eIF1A, and a single ITA

137 e critical biological pathways including the EIF2, eIF4/p70S6K, mTOR signaling and mitochondrial dysf

138 When TC is formed with unphosphorylated eIF2, eIF5 can out-compete eIF2B to stabilize TC/eIF5 co

139 t inhibits the translation initiation factor eIF2 (eukaryotic initiation factor 2).

140 to the interferon signaling pathway and the eIF2 family was evaluated at two- and six-days post infe

141 itiation the eukaryotic initiation factor 2 (eIF2) forms a ternary complex (TC) with GTP and the init

142 Phosphorylation converts eIF2 from a substrate into an inhibitor of eIF2B.

143 I displacement factor (GDF) that can recruit eIF2 from the eIF2*GDP/eIF5 GDI complex prior to GEF act

144 verts protein synthesis initiation factor 2 (eIF2) from a GDP-bound form to the active eIF2-GTP compl

145 consequences of MEHMO syndrome mutations on eIF2 function, we generated a yeast model of the human e

146 g with the key steps by which eIF5 regulates eIF2 function.

147 horylate the eukaryotic initiation factor-2 (eIF2) function in translational control and drive differ

148 eIF2 GDP/GTP status is regulated by eIF5 (GAP and GDI fu

149 t AUG codons, from which Pi is released from eIF2 . GDP . Pi.

150 ICs are less stable owing to dissociation of eIF2*GDP from initiator tRNA, and eIF5B is then required

151 otide exchange factor that recycles inactive eIF2*GDP to active eIF2*GTP.

152 2, thereby altering the off-rate of GDP from eIF2*GDP/eIF5 complexes.

153 onitor the kinetics of eIF2 release from the eIF2*GDP/eIF5 GDI complex and determine the effect of eI

154 factor (GDF) that can recruit eIF2 from the eIF2*GDP/eIF5 GDI complex prior to GEF action.

155 and eIF5, thought to primarily function with eIF2-GDP and TC respectively.

156 components may play a role in the release of eIF2-GDP from the ribosome following AUG recognition.

157 Following GTP hydrolysis, eIF2-GDP is recycled back to TC by its guanine nucleotid

158 for the complex of eIF2B with its substrate, eIF2-GDP, reaction intermediates, apo-eIF2 and eIF2-GTP,

159 affinity to Met-tRNA(i) compared to that for eIF2-GDP, suggesting that MFC components may play a role

160 s to allow subsequent phosphate release from eIF2-GDP.

161 eukaryotic translation initiation factor 2 (eIF2) gene family is a likely candidate for control of v

162 ion of eIF2alpha reduces the level of active eIF2, globally inhibiting translation.

163 the GTPase activating protein (GAP) for the eIF2 . GTP . Met-tRNAi (Met) ternary complex with a crit

164 x containing eukaryotic initiation factor 2 (eIF2), GTP, and methionine-charged initiator methionyl-t

165 , and mutations within eIF3b/i/g destabilize eIF2*GTP*Met-tRNAi binding to the PIC.

166 s also regulate hydrolysis of the GTP in the eIF2*GTP*Met-tRNAiMet complex to GDP and Pi.

167 re critical for efficient recruitment of the eIF2*GTP*Met-tRNAiMet ternary complex to the ribosome an

168 or that recycles inactive eIF2*GDP to active eIF2*GTP.

169 by way of a ternary complex (TC) comprising eIF2, GTP and Met-tRNA(i).

170 ow that eIF2B can compete with Met-tRNAi for eIF2-GTP and can destabilize TC.

171 eIF2-GTP binds Met-tRNAi to form the eIF2-GTP*Met-tRNAi

172 2 (eIF2) from a GDP-bound form to the active eIF2-GTP complex.

173 eIF5 for TC and identify that phosphorylated eIF2-GTP translation initiation intermediate complexes c

174 )) binding (in the ternary complex [TC] with eIF2-GTP) to reconstituted preinitiation complexes (PICs

175 eIF2-GTP binds Met-tRNAi to form the eIF2-GTP*Met-tRNAi ternary complex (TC), which is recrui

176 F2-GDP, reaction intermediates, apo-eIF2 and eIF2-GTP, and product, TC, with direct implications for

177 omal subunit, in a ternary complex (TC) with eIF2-GTP, is stimulated by eukaryotic initiation factor

178 factor 2, which stimulates formation of the eIF2-GTP-Met-tRNA(i)(Met) ternary complex (TC) in a mann

179 complex formation and decreases the level of eIF2-GTP-Met-tRNA(i)(Met) ternary complexes.

180 contributions of eIF1, eIF1A, eIF3, and the eIF2-GTP-Met-tRNAi ternary complex (TC) in stabilizing t

181 This allows continued formation of the eIF2-GTP-Met-tRNAi ternary complex and unabated global t

182 subunit, eIF1, eIF1A, eIF3, ternary complex (eIF2-GTP-Met-tRNAi), and eIF5.

183 d GCN4 expression, an indicator of defective eIF2-GTP-Met-tRNAiMet complex formation, and, likewise,

184 ow availability of the eIF2 ternary complex (eIF2-GTP-tRNAi) by affecting the interaction of eIF2 wit

185 itiation by restricting the levels of active eIF2-GTP/Met-tRNAi ternary complexes (TC).

186 ng protein partner eIF2 via interaction with eIF2.GTP at an early step in translation initiation.

187 iphosphate-initiator methionyl transfer RNA (eIF2.GTP.Met-tRNA(i )(Met)).

188 o, R55G-R57E accelerated dissociation of the eIF2.GTP.Met-tRNAi ternary complex (TC) from reconstitut

189 eversible GTP hydrolysis (Pi release) by the eIF2.GTP.Met-tRNAi ternary complex (TC), rearrangement o

190 tic pre-initiation complex (PIC) bearing the eIF2.GTP.Met-tRNAi(Met) ternary complex (TC) scans the m

191 a GTPase accelerating protein (GAP) for the eIF2.GTP.tRNA(i)(Met) ternary complex within the ribosom

192 with eIF3, eIF1, and eIF1A, Met-tRNA(Met)(i)/eIF2/GTP binds to 40S subunits yielding 43S preinitiatio

193 Since assembly of the met-tRNAi/eIF2/GTP ternary complex is integral to protein synthesi

194 First, eIF5 binds eIF2/GTP/Met-tRNA(i)(Met) ternary complex (TC), promotin

195 nize eIF2 reactivation by competing with the eIF2 guanine exchange factor (GEF), eIF2B.

196 ition of the drug ISRIB, an activator of the eIF2 guanine nucleotide exchange factor, rescues the cel

197 rotein synthesis and promotes ISR by binding eIF2, hydrolyzing GTP, and interfering with TC formation

198 of tRNAiMet restored Met-tRNAiMet binding to eIF2 in vivo and rescued the growth defect in the eIF2ga

199 Phosphorylated eIF2 (p-eIF2) in turn sequesters the eIF2-specific guanine excha

200 substrate, the translation initiation factor eIF2, in vitro.

201 of Ligatin, respectively) promote efficient eIF2-independent recruitment of Met-tRNA(Met)(i) to 40S/

202 It reveals that eIF2 interacts with the 40S subunit via its alpha subuni

203 sponse to various cellular stresses converts eIF2 into a competitive inhibitor of eIF2B, which trigge

204 eIF2 is a guanosine triphosphatase that becomes activate

205 The general translation initiation factor eIF2 is a major translational control point.

206 Eukaryotic initiation factor 2 (eIF2) is a G protein critical for translation.

207 Eukaryotic translation initiation factor 2 (eIF2) is a heterotrimeric GTPase, which plays a critical

208 Eukaryotic initiation factor 2 (eIF2) is a key integrator of cellular stress responses a

209 eukaryotic translation initiation factor 2 (eIF2) is central to the onset of protein synthesis and i

210 nt limitation, leading to activation of this eIF2 kinase and translational control.

211 show that activating EIF2 signaling through EIF2 kinase inhibition mitigated stress-induced behavior

212 Second, this eIF2 kinase is activated by select uncharged tRNAs, whic

213 ulation and translational control allows the eIF2 kinase pathway to selectively repress or activate k

214 is that coincided with activation of another eIF2 kinase PKR-like endoplasmic reticulum kinase (PERK)

215 he importance of eIF2Balpha in mediating the eIF2 kinase translation-inhibitory activity and may prov

216 etion by the eukaryotic initiation factor 2 (eIF2) kinase GCN2.

217 get that integrates signaling from different eIF2 kinases and their respective stress signals, the eI

218 Because there are multiple mammalian eIF2 kinases, each responding to different stress arrang

219 tivate kinases that phosphorylate the GTPase eIF2 leading to inhibition of its exchange factor eIF2B.

220 the eukaryotic translation initiation factor eIF2, leading to global downregulation of translation to

221 ino acid starvation, GCN2 phosphorylation of eIF2 leads to repression of general translation and init

222 ex and unabated global translation at high p-eIF2 levels that would otherwise cause translational arr

223 eIF2 localizes to eIF2B bodies and shuttles within these

224 mplicated in eukaryotic initiation factor 2 (eIF2)-mediated translational control, but its physiologi

225 in mood-related phenotypes, (2) deregulated EIF2-mediated protein translation may represent a mechan

226 strated that a single uORF is sufficient for eIF2-mediated translation control in both cases.

227 Two eIF2 molecules bind opposite sides of an eIF2B hetero-de

228 Phosphorylated eIF2 (p-eIF2) in turn sequesters the eIF2-specific guani

229 Phosphorylation of the alpha-subunit of eIF2 (p-eIF2alpha), the central component of the integra

230 Inhibition of eIF2-P and translational control reduced viability follo

231 Although eIF2-P elicits translational control in response to many

232 that UVB irradiation is a potent inducer of eIF2-P in keratinocytes, leading to decreased levels of

233 dicating that translation repression through eIF2-P is central to keratinocyte survival.

234 orylation of eukaryotic initiation factor 2 (eIF2-P) that causes decreased global protein synthesis c

235 Central to the changes in gene expression, eIF2 phosphorylation also enhances translation of ATF4,

236 4.5beta is unable to counteract PKR-mediated eIF2 phosphorylation but does not interfere with ICP34.5

237 Interestingly, hepatic eIF2 phosphorylation by MR was uncompromised in Gcn2(-/-

238 However, in yeast, the effect of eIF2 phosphorylation can be mimicked by eIF5 overexpress

239 We also discuss how eIF2 phosphorylation contributes to the maintenance of l

240 Enhanced eIF2 phosphorylation during stress facilitates ribosome

241 In this study, we show that eIF2 phosphorylation induces preferential translation of

242 Failure of eIF2B to sense eIF2 phosphorylation likely leads to unregulated unfolde

243 eIF2 phosphorylation thereby represses translation.

244 ion factor whose translation is activated by eIF2 phosphorylation through delayed re-initiation invol

245 olly or partially resistant to inhibition by eIF2 phosphorylation, despite requiring Met-tRNA(Met)(i)

246 In the absence of stress and low eIF2 phosphorylation, translation of the uORF serves as

247 ants render the eIF2B complex insensitive to eIF2 phosphorylation, which occurs under stress conditio

248 Those identified so far prevent or reverse eIF2 phosphorylation.

249 te to nucleotide exchange and its control by eIF2 phosphorylation.

250 ficient eIF2 recycling and its regulation by eIF2 phosphorylation.

251 5, which is preferentially translated during eIF2 phosphorylation.

252 upstream open reading (uORFs) in response to eIF2 phosphorylation.

253 In eukaryotes, initiation factor 2 (eIF2) plays an important role in translation initiation

254 orylation of eukaryotic initiation factor-2 (eIF2) rapidly reduces protein synthesis, which lowers en

255 ion inhibition (GDI) activity can antagonize eIF2 reactivation by competing with the eIF2 guanine exc

256 F2B GDF function in the context of efficient eIF2 recycling and its regulation by eIF2 phosphorylatio

257 cific guanine exchange factor eIF2B to block eIF2 recycling, thereby halting translation initiation a

258 by eIF2B mutations that, like phosphorylated eIF2, reduce its activity.

259 development of AD through the activation of eIF2, regulation of eIF4 and p70S6K signaling, and mTOR

260 of the ancient Obg family of GTPases, is an eIF2-regulatory protein that inhibits protein synthesis

261 he genetic line differences in expression of eIF2-related genes may contribute to their differential

262 e exchange assays to monitor the kinetics of eIF2 release from the eIF2*GDP/eIF5 GDI complex and dete

263 PERK phosphorylation of eIF2 represses global protein synthesis, lowering influx

264 y the CUGBP1-eukaryotic initiation factor 2 (eIF2) repressor complex.

265 hich phosphorylation of the alpha subunit of eIF2 results in a coincident global reduction in transla

266 nd heterodecameric complex that functions as eIF2's dedicated nucleotide exchange factor.

267 the phosphorylation of the alpha subunit of eIF2 (Ser51), resulting in inhibition of global protein

268 the integrated stress response phosphorylate eIF2 serine-51, inhibiting nucleotide exchange by eIF2B.

269 ingly, drugs that inhibit the ISR can rescue eIF2 shuttling in a manner correlating to levels of eIF2

270 In contrast, smaller bodies show increased eIF2 shuttling in response to stress, which is accompani

271 lly, we found that they selectively utilized EIF2 signaling and oxidative phosphorylation pathways.

272 erability of SST neurons and (3) that global EIF2 signaling has antidepressant/anxiolytic potential.

273 with our yeast-based findings, YopJ reduces eIF2 signaling in response to endoplasmic reticulum stre

274 how in mammalian cells that induction of the eIF2 signaling pathway occurs following infection with b

275 Thus, our findings reveal a noncanonical eIF2 signaling pathway that controls selective changes i

276 forced abstinence length including RELN, the Eif2 signaling pathway, synaptogenesis and neurogenesis

277 our data indicate that the highly conserved eIF2 signaling pathway, which is vitally important for a

278 expression, are both dependent on an intact eIF2 signaling pathway.

279 We then show that activating EIF2 signaling through EIF2 kinase inhibition mitigated

280 pectedly, we found that cells with defective eIF2 signaling were more susceptible to bacterial invasi

281 nscriptomic responses included alteration of EIF2 signaling, steroid biosynthesis, ribosome biogenesi

282 o-Virus group by 100 genes, some involved in eIF2 signaling.

283 tion through eukaryotic initiation factor 2 (EIF2) signaling, a pathway previously implicated in neur

284 Gs with stress markers TIA-1, CUGBP1, and ph-eIF2, site-specific mutagenesis, and examinations of RNA

285 rylated eIF2 (p-eIF2) in turn sequesters the eIF2-specific guanine exchange factor eIF2B to block eIF

286 Moreover, the combined overexpression of eIF2 subunits rescued an otherwise inviable cdc123 delet

287 in budding yeast reduced the association of eIF2 subunits, diminished polysome levels, and increased

288 orylation results in low availability of the eIF2 ternary complex (eIF2-GTP-tRNAi) by affecting the i

289 taepsilon)2 decamers show greater binding to eIF2 than to eIF2B(betagammadeltaepsilon) tetramers, whi

290 s eIF5 GDI stabilizing nucleotide binding to eIF2, thereby altering the off-rate of GDP from eIF2*GDP

291 ctivates the eukaryotic initiation factor 2 (eIF2) translation initiation factor upon binding to vira

292 rotein homeostasis induce phosphorylation of eIF2, triggering repression of global protein synthesis

293 atic platform upon which one or two flexible eIF2 trimers bind and align with eIF2B's bipartite catal

294 The structures reveal that eIF2 undergoes large rearrangements to promote binding o

295 or (GEF) for its GTP-binding protein partner eIF2 via interaction with eIF2.GTP at an early step in t

296 t nucleotides and initiator tRNA to purified eIF2 we show that the eIF2beta mutation does not affect

297 Based on these findings and the structure of eIF2, we propose that the I259M mutation impairs Met-tRN

298 n order to trigger release of phosphate from eIF2, which converts the latter to its GDP-bound state.

299 proteins we demonstrate that eIF2B binds to eIF2 with equal affinity irrespective of the presence or

300 2-GTP-tRNAi) by affecting the interaction of eIF2 with its GTP-GDP exchange factor eIF2B.