ライフサイエンスコーパス: eIF2

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

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

3 ects is to control translation by inhibiting eIF2.

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

5 g guanine nucleotide exchange on its partner eIF2.

6 release, and changes in the conformation of eIF2.

7 ichiometry and interactions within eIF2B and eIF2.

8 the alpha-subunit of the translation factor eIF2.

9 of eukaryotic translation initiation factor, eIF2.

10 , 5MP1 is not a GEF but a weak GDI for yeast eIF2.

11 e HEAT domain, mediates its interaction with eIF2.

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

13 n to rapidly induce Gcn2p phosphorylation of eIF2.

14 UGBP1) and the translation initiation factor eIF2.

15 e recruitment of initiation factors eIF3 and eIF2.

16 eta subunit of translation initiation factor eIF2.

17 eta subunits of eukaryotic initiation factor eIF2.

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

19 through a translational mechanism involving eIF2.

20 gulation by phosphorylation of the substrate eIF2.

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

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

23 ssion indicating that Cdc123 is critical for eIF2 activity.

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

25 f HEp3 cells that displays strong basal PERK-eIF2 alpha activation, reverts their quiescent phenotype

26 ased PERK activation is linked to enhanced p-eIF2 alpha levels, translational repression, and a decre

27 ncreatic endoplasmic reticulum kinase (PERK)-eIF2 alpha signaling, a component of the endoplasmic ret

28 rcinoma T-HEp3 cells, which display low PERK-eIF2 alpha signaling, inducible activation of an Fv2E-PE

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

30 ndent protein kinase-like ER-integral (PERK) eIF2 alpha-kinase, and induction of hepatic protein ubiq

31 r eEF2 and the translation initiation factor eIF2 alpha.

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

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

39 vating eukaryotic initiation factor 2-alpha (eIF2-alpha), to examine the mechanism by which low and h

40 activation and increased phosphorylation of eIF2-alpha, whereas the reduced susceptibility of normal

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

42 indings reveal that the essential process of eIF2(alphaP) dephosphorylation is the predominant role o

43 how that eIF5 is a critical component of the eIF2(alphaP) regulatory complex that inhibits the activi

44 tase catalytic subunits of the PPP1 class to eIF2(alphaP), but the significance of their contribution

45 response to stress, but dephosphorylation of eIF2(alphaP), which terminates signaling in this pathway

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

65 orylation of eukaryotic initiation factor-2 (eIF2) and the general amino acid control pathway.

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

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

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

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

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

71 r variable expression of ATF4 in response to eIF2 approximately P during different stress conditions

72 Although eIF2 approximately P elicits translational control in re

73 for translation during eIF2 approximately P. eIF2 approximately P enhances cell survival in response

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

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

76 ronmental stresses, phosphorylation of eIF2 (eIF2 approximately P) represses global translation coinc

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

78 not increase ATF4 expression despite robust eIF2 approximately P.

79 not increase ATF4 expression despite robust eIF2 approximately P.

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

81 s ATF4 mRNA available for translation during eIF2 approximately P. eIF2 approximately P enhances cell

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

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

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

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

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

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

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

89 utions in beta/Gcd7 and eIF2alpha all impair eIF2 binding to eIF2B without reducing epsilon/Gcd6 abun

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

91 Translation initiation factor 2 (eIF2) binds Met-tRNA(i)(Met) to the 40S ribosomal subuni

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

93 are required for eIF5-induced hydrolysis of eIF2-bound GTP and/or subunit joining.

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

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

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

97 We found that the age-associated CUGBP1-eIF2 complex binds to the 5' region of HDAC1 mRNA and in

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

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

100 2 complex, nearly comparable to that of eIF5:eIF2 complex produced by eIF5 overexpression.

101 a suggest that V1 does not interact with the eIF2 complex, a requisite for eIF2B inhibition by eIF2al

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

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

104 levels, leads to the reduction of the CUGBP1-eIF2 complex, normalization of HDAC1 levels, and inhibit

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

106 , which enhances the formation of the CUGBP1-eIF2 complex.

107 ice, which display high levels of the CUGBP1-eIF2 complex.

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

109 nctions of the 20S proteasome and the CUGBP1-eIF2 complexes, the stability of short-lived proteins an

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

111 1, dissociation of 48S complexes formed with eIF2 could be out-competed by efficient subunit joining.

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

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

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

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

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

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

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

119 Phosphorylation of eIF2 during stress delays translation reinitiation, allo

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

121 t environmental stresses, phosphorylation of eIF2 (eIF2 approximately P) represses global translation

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

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

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

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

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

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

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

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

130 g a subunit of translation initiation factor eIF2, eIF2alpha.

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

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

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

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

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

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

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

138 he sensitivity of 48S complexes assembled by eIF2/eIF3- and eIF5B/eIF3-mediated mechanisms to eIF1-in

139 Although 48S complexes assembled both by eIF2/eIF3- and eIF5B/eIF3-mediated Met-tRNA(iMet) recrui

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

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

142 -tuned by eIF2 phosphorylation and the novel eIF2/eIF5 complex lacking tRNA(i)(Met).

143 s by phosphorylation of the alpha-subunit of eIF2 (eukaryotic initiation factor 2), which inhibits it

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

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

146 latory functions of eIF5 in the recycling of eIF2 from its inactive eIF2.GDP state between successive

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

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

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

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

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

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

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

154 2, thereby altering the off-rate of GDP from eIF2*GDP/eIF5 complexes.

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

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

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

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

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

160 RES near the 40S ribosomal E-site to promote eIF2-GDP release, facilitating 80S ribosome assembly.

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

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

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

164 5 in the recycling of eIF2 from its inactive eIF2.GDP state between successive rounds of translation

165 in promoting eIF5-induced GTP hydrolysis and eIF2/GDP release from the initiation complex.

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

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

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

169 tors accelerate the rate of ternary complex (eIF2*GTP*Met-tRNA(i)(Met)) binding to 40S but only eIF1A

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

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

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

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

174 2 (eIF2) from a GDP-bound form to the active eIF2-GTP complex.

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

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

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

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

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

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

181 he yeast multifactor complex (eIF1-eIF3-eIF5-eIF2-GTP-Met-tRNA(i)(Met)).

182 preinitiation complexes containing eIF3 and eIF2-GTP-Met-tRNA(iMet) to bind directly to the initiati

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

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

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

186 RNA(i)(Met) in the ternary complex (TC) with eIF2.GTP and also to block initiation at UUG codons.

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

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

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 e roles throughout initiation: it stimulates eIF2/GTP/Met-tRNA(i)(Met) attachment to 40S ribosomal su

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

196 eukaryotic initiation factor (eIF) 3 and the eIF2/GTP/Met-tRNA(i)(Met) ternary complex.

197 nd CTT both enhance ribosomal recruitment of eIF2/GTP/Met-tRNA(i)(Met), but have opposite effects on

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

199 g epsilon/Gcd6 abundance in the native eIF2B-eIF2 holocomplex.

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

201 the S1 domain of the alpha-subunit of yeast eIF2 in vitro and to interact with eIF2Balpha/GCN3 in vi

202 periment 1, asparaginase increased hepatic p-eIF2 in wild-type mice and mice with a liver-specific PE

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

204 We further demonstrate eIF2-independent assembly of 80 S initiation complex on

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

206 ously for analogous complexes assembled with eIF2, indicating that domain II is essential for general

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

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

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

210 imate that approximately 15% of the cellular eIF2 is found in TC during rapid growth in a complex ric

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

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

213 orylation of eukaryotic initiation factor 2 (eIF2) is an important mechanism regulating global and ge

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

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

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

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

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

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

220 Central to the eIF2 kinase response is the preferential translation of

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

222 AC) genes whose transcription depends on the eIF2 kinase, Gcn2.

223 Given its importance to pathogenesis, eIF2 kinase-mediated stress responses may provide opport

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

225 of this study were to assess the role of the eIF2 kinases and protein kinase R-like endoplasmic retic

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

227 These results demonstrate that eIF2 kinases direct the translational expression of mult

228 he regulation of protein translation through eIF2 kinases is associated with development, 2) eIF2alph

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

230 Both eIF2 kinases, protein kinase-like endoplasmic reticulum

231 ose translational expression is regulated by eIF2 kinases.

232 Furthermore, we have characterized novel eIF2 kinases; one in the endoplasmic reticulum and a lik

233 ylation of eukaryotic initiation factor 2 (p-eIF2) leading to increased mRNA levels of asparagine syn

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

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

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

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

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

239 ic initiation factor (eIF) 3 and the ternary eIF2/Met-tRNA(i)(Met)/GTP complex and subsequently domai

240 , asparaginase but not rapamycin increased p-eIF2, p-ERK1/2, p-Akt, and mRNA levels of asparagine syn

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

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

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

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

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

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

247 zed TC formation appears to be fine-tuned by eIF2 phosphorylation and the novel eIF2/eIF5 complex lac

248 4.5beta is unable to counteract PKR-mediated eIF2 phosphorylation but does not interfere with ICP34.5

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

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

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

252 Enhanced eIF2 phosphorylation during stress facilitates ribosome

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

254 During non-stressed conditions, when eIF2 phosphorylation is low, ribosomes reinitiate transl

255 tein synthesis is a consequence of increased eIF2 phosphorylation resulting from PRL3 expression.

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

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

258 in response to cellular stress that induces eIF2 phosphorylation, indicating that this regulatory me

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

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

261 ficient eIF2 recycling and its regulation by eIF2 phosphorylation.

262 5, which is preferentially translated during eIF2 phosphorylation.

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

264 teasome inhibition, by a mechanism requiring eIF2 phosphorylation.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

290 vious studies identified Sui(-) mutations in eIF2 that enhanced initiation from a noncanonical UUG co

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

292 sis are sensitive to the availability of the eIF2 translation initiation complex and to changes in th

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

294 lease of phosphate from the G-protein factor eIF2, triggering downstream events in initiation.

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

296 s with the macromolecular composition of the eIF2.tRNA(i)(Met.)GTP complex (TC) and the multifactor c

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

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

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

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