ライフサイエンスコーパス: eIF2alpha

1 eIF2alpha phosphorylation is upregulated by TDP-43 toxic

2 eIF2alpha phosphorylation-induced stress granule (SG) fo

3 eIF2alpha plays a central role in the integrated stress

4 d through the general control nonrepressed-2 eIF2alpha kinase.

5 subunit of translation initiation factor 2 (eIF2alpha) phosphorylation, activating transcription fac

6 eukaryotic translation initiation factor 2 (eIF2alpha) resulting in inhibition of general protein sy

7 rylation of translation initiation factor 2 (eIF2alpha) terminates signalling in the mammalian integr

8 eukaryotic translation initiation factor 2 (eIF2alpha) to activate the integrated stress response (I

9 eukaryotic translation initiation factor 2 (eIF2alpha), is an important protective mechanism cells u

10 a subunit of eukaryotic initiation factor 2 (eIF2alpha).

11 a subunit of eukaryotic initiation factor 2 (eIF2alpha).

12 tream of eukaryotic initiation factor 2alpha eIF2alpha phosphorylation.

13 ryotic translation initiation factor 2alpha (eIF2alpha) are associated with pancreatic beta-cell fail

14 ion of translation initiation factor 2alpha (eIF2alpha) attenuates global protein synthesis but enhan

15 tion of eukaryotic initiation factor 2alpha (eIF2alpha) controls transcriptome-wide changes in mRNA t

16 ryotic translation initiation factor 2alpha (eIF2alpha) kinase (HRI).

17 ryotic translation initiation factor 2alpha (eIF2alpha) mouse embryonic fibroblasts (MEFs); moreover,

18 ryotic translation initiation factor 2alpha (eIF2alpha) phosphatase, is a RIDD substrate.

19 ryotic translation initiation factor 2alpha (eIF2alpha) phosphorylation-dependent integrated stress r

20 tion of eukaryotic initiation factor 2alpha (eIF2alpha), resulting in rapid inhibition of protein syn

21 on in a eukaryotic initiation factor 2alpha (eIF2alpha)-independent manner.

22 tion of eukaryotic initiation factor 2alpha (eIF2alpha).

23 arasite eukaryotic initiation factor-2alpha (eIF2alpha), leading to repression of general translation

24 te in PKR binding, pTRS1 bound an additional eIF2alpha kinase, heme-regulated inhibitor (HRI), and in

25 yotic translation initiation factor 2 alpha (eIF2alpha) bidirectionally regulates auditory but not vi

26 ng the eukaryotic initiation factor 2 alpha (eIF2alpha) or other signal transduction cascades.

27 yotic translation initiation factor 2 alpha (eIF2alpha).

28 aryotic translation initiation factor alpha (eIF2alpha) phosphorylation earlier and more strongly tha

29 aryotic translation initiation factor alpha (eIF2alpha)-CEBP homologous protein (CHOP) signaling and

30 s have been attributed to its function as an eIF2alpha kinase.

31 ription is mediated at least partially by an eIF2alpha-dependent increase in ATF4 expression.

32 nandamide increased ceramide synthesis in an eIF2alpha-dependent manner, and inhibited insulin-induce

33 By contrast, inhibition of an eIF2alpha kinase or blocking the translational program c

34 CReP]) encoding the regulatory subunit of an eIF2alpha-specific phosphatase in two siblings affected

35 ISR-enhanced RAN translation requires an eIF2alpha phosphorylation-dependent alteration in start

36 tion of OLA1 expression or treatment with an eIF2alpha dephosphorylation inhibitor, suggesting that O

37 strated by the attenuation of IRE-1alpha and eIF2alpha phosphorylation.

38 ated, activating transcription factor 6, and eIF2alpha were activated with subsequent overexpression

39 The R658C mutation decreases PP1 binding and eIF2alpha dephosphorylation and results in beta-cell apo

40 rk, their downstream effectors Grp78/BiP and eIF2alpha in ERG transgenic mouse prostate glands indica

41 ent PKR-dsRNA binding, PKR dimerization, and eIF2alpha phosphorylation.

42 revealed that DHX29 may rearrange eIF1A and eIF2alpha in key nucleotide context positions of ribosom

43 sensor PERK (protein kinase-like kinase) and eIF2alpha-ATF4-CHOP signaling.

44 ibosomal RNA, and phosphorylation of PKR and eIF2alpha that correlated with a approximately 15-fold i

45 In addition, both PKR and eIF2alpha were phosphorylated during infection when pTRS

46 f eIF2alpha by interacting with both PP1 and eIF2alpha through independent binding motifs.

47 osphatase 1 catalytic subunit (PP1alpha) and eIF2alpha to assemble a phosphatase complex catalyzing e

48 e interface between 40S protein Rps5/uS7 and eIF2alpha between open and closed states; however, its i

49 Recently, both eIF2alpha and its kinases were found to play a role in n

50 s stress granule assembly that required both eIF2alpha phosphorylation and G3BP.

51 stress wherein TC recycling is attenuated by eIF2alpha phosphorylation.

52 neurodegenerative diseases characterized by eIF2alpha phosphorylation, SG formation, and cognitive l

53 we identified that translational control by eIF2alpha phosphorylation (p-eIF2alpha) regulates cocain

54 e preferentially translated mRNAs induced by eIF2alpha-P is that encoding the transcription factor CH

55 karyotic initiation factor phosphorylated by eIF2alpha kinases under stress conditions.

56 steps in translation initiation regulated by eIF2alpha phosphorylation and the mTOR/4E-BP pathway, re

57 ism for these critical adaptive responses by eIF2alpha-P involved induced expression of CDKN1A encodi

58 ty of a translation initiation factor called eIF2alpha might be partly responsible for the increased

59 to assemble a phosphatase complex catalyzing eIF2alpha dephosphorylation and resumption of protein sy

60 amino acid point mutations in the conserved eIF2alpha binding domain of PKR disrupted pTRS1 binding

61 stent with a critical role for the conserved eIF2alpha contact site in PKR binding, pTRS1 bound an ad

62 relied on the inhibition of the constitutive eIF2alpha dephosphorylation and down-regulation of the p

63 on of UPR by the GADD34- and CReP-containing eIF2alpha phosphatases to control cell viability.

64 ADD34 levels in a manner involving decreased eIF2alpha phosphorylation.

65 Mice with decreased eIF2alpha phosphorylation (eIF2alpha(+/S51A)) exhibit re

66 n and recruitment of NCK1 to eIF2, decreases eIF2alpha phosphorylation and bolsters TC recycling.

67 Here, we discover a role for deficient eIF2alpha signaling in DYT1 dystonia, a rare inherited g

68 directs PP1 to specifically dephosphorylate eIF2alpha.

69 CReP (PPP1R15B) function to dephosphorylate eIF2alpha-P and restore protein synthesis.

70 otein phosphatase 1 (PP1) to dephosphorylate eIF2alpha.

71 ons in cis to target GLC7 to dephosphorylate eIF2alpha.

72 A family of different eIF2alpha kinases function in the integrative stress res

73 uS7 substitutions disrupting eIF2alpha contacts favored in the open complex increase

74 diated translation control mechanisms during eIF2alpha-P and additionally illustrate the roles that p

75 ndings support the concept that dysregulated eIF2alpha phosphorylation, whether decreased by mutation

76 t of the translation initiation factor eIF2 (eIF2alpha) can promote apoptosis.

77 hosphorylation of the alpha subunit of eIF2 (eIF2alpha approximately P), which represses global trans

78 hosphorylation of the alpha subunit of eIF2 (eIF2alpha-P) represses global protein synthesis, coincid

79 hosphorylation of the alpha subunit of eIF2 (eIF2alpha-P), which represses translation initiation and

80 ress response, phosphorylation of eIF2alpha (eIF2alpha-P) reduces protein synthesis to conserve resou

81 ress response, phosphorylation of eIF2alpha (eIF2alpha-P) reduces protein synthesis while concomitant

82 n through GCN2 phosphorylation of eIF2alpha (eIF2alpha-P).

83 to encode a non-phosphorylatable eIF2alpha (eIF2alpha(S51A)).

84 lic variability of the Eif2s1 gene (encoding eIF2alpha) on reward-related neuronal responses in human

85 Enhanced eIF2alpha-P during stress directs ribosome bypass of the

86 etion at sites enriched for PPP1R15 enhanced eIF2alpha phosphorylation and the downstream ISR.

87 ylation of the translation initiation factor eIF2alpha (p-eIF2alpha) accounts for adolescent hypersen

88 the eukaryotic translation initiation factor eIF2alpha and causes translational shutdown to create ro

89 ation of protein synthesis initiation factor eIF2alpha at serine 51 was increased in IFN-treated Adar

90 phorylation of translation initiation factor eIF2alpha inhibition of protein synthesis and apoptosis.

91 ctivity of the translation initiation factor eIF2alpha underlies the hypersensitivity of adolescent m

92 nactivates the translation initiation factor eIF2alpha via phosphorylation, while OAS induces the end

93 sphorylation of eukaryotic initiation factor eIF2alpha, a hallmark of stress pathway activation.

94 s phosphorylate eukaryotic initiation factor eIF2alpha, enabling the translation of stress response g

95 phorylation of translation initiation factor eIF2alpha, which promotes the formation of discrete cyto

96 ylation of the translation initiation factor eIF2alpha.

97 ed phosphorylation of the translation factor eIF2alpha.

98 ng eukaryotic translation initiation factor (eIF2alpha), and derepressing GM-CSF mRNA translation.

99 the phosphorylation of Plasmodium falciparum eIF2alpha factor, an eukaryotic initiation factor phosph

100 In this study, we elucidated a mechanism for eIF2alpha-P cytoprotection in response to UVB in human k

101 athogenic role and therapeutic potential for eIF2alpha pathway perturbations.

102 irus, suggesting an IFN-independent role for eIF2alpha kinases during infection.

103 ntial for the recruitment of PKR to SGs, for eIF2alpha phosphorylation driven by PKR, and for nucleat

104 Furthermore, eIF2alpha-P dephosphorylation, assessed by a kinase shut

105 In the absence of GADD34, eIF2alpha phosphorylation is persistently enhanced and t

106 The GCN2-eIF2alpha pathway is expressed in many tissues, includin

107 The GCN2-eIF2alpha signaling pathway is specifically activated by

108 In addition, activation of the GCN2-eIF2alpha-ATF4 and PERK-eIF2alpha-ATF4 signaling pathway

109 cific MEK1/ERK2 signaling, induction of GCN2/eIF2alpha phosphorylation, and ATF4 expression, which ov

110 ced PPARbeta/delta and activation of the HRI-eIF2alpha-ATF4 pathway.

111 In this issue, Tsuyama et al. identify eIF2alpha phosphorylation as a critical regulator of mit

112 (iii) eIF2alpha is confirmed as the congenerous target of miR-

113 w that in addition to turning off the immune/eIF2alpha phosphorylation-dependent inhibition of transl

114 The H2S-induced increase in eIF2alpha phosphorylation was mediated at least in part

115 g hyperosmotic stress despite an increase in eIF2alpha phosphorylation.

116 culum, and inhibits PP1 activity to increase eIF2alpha phosphorylation and ATF4 levels.

117 IRE1alpha-dependent manner, which increased eIF2alpha phosphorylation and consequently attenuated pr

118 anical, pain sensitivity, whereas increasing eIF2alpha phosphorylation has the opposite effect on the

119 Induced eIF2alpha phosphorylation by the general control nondere

120 ART-induced eIF2alpha phosphorylation is mediated by the Plasmodium

121 entially translated following stress-induced eIF2alpha-P by a mechanism mediated in part by upstream

122 initiation stringency during stress-induced eIF2alpha-P, we observed facilitated ribosome bypass of

123 ific, as LCMV is unable to similarly inhibit eIF2alpha phosphorylation.

124 eme-regulated inhibitor (HRI), and inhibited eIF2alpha phosphorylation in response to an HRI agonist.

125 recrudescence following ART, and inhibiting eIF2alpha dephosphorylation renders parasites less sensi

126 Moreover, selectively inhibiting eIF2alpha-mediated translational control with a small mo

127 in the polymeric status of actin, as was its eIF2alpha-directed phosphatase activity, while localised

128 g the adaptive stage of the UPR, PERK kinase-eIF2alpha axis activates Yap, while prolonged ER stress-

129 ndent upon a heme-regulated inhibitor kinase/eIF2alpha/activating transcription factor 4 (ATF4) signa

130 econstituted IPA-activation of PERK-mediated eIF2alpha phosphorylation from purified components.

131 In this report, we map a novel eIF2alpha-binding motif to the C terminus of GADD34 in a

132 rected oxidative stressor, in the absence of eIF2alpha phosphorylation suggest other roles for GADD34

133 al translation of its mRNA in the absence of eIF2alpha phosphorylation.

134 in response to multiple known activators of eIF2alpha-P and likely serves to facilitate stress adapt

135 K inhibition may be linked to attenuation of eIF2alpha phosphorylation and reveals a previously unkno

136 Pharmacological attenuation of eIF2alpha phosphorylation decreases thermal, but not mec

137 Restoring translational control of eIF2alpha holds the promise to rejuvenate adult brain pl

138 thologs direct specific dephosphorylation of eIF2alpha by interacting with both PP1 and eIF2alpha thr

139 apable of mediating the dephosphorylation of eIF2alpha, and the virus was capable of controlling the

140 protein phosphatase for dephosphorylation of eIF2alpha-P to restore protein synthesis.

141 involve GADD34-mediated dephosphorylation of eIF2alpha-P.

142 SRIB makes cells resistant to the effects of eIF2alpha phosphorylation and enhances long-term memory

143 The impact of eIF2alpha phosphorylation (p-eIF2alpha) on thermal thres

144 ism for dystonia pathogenesis, impairment of eIF2alpha signaling, a pathway known for its roles in ce

145 CReP expression occurs independent of eIF2alpha-P via an uORF that allows for translation rein

146 SGs were formed independently of eIF2alpha phosphorylation, and their appearance was corr

147 ased CReP expression caused the induction of eIF2alpha phosphorylation and the attenuation of protein

148 Moreover, we show that induction of eIF2alpha phosphorylation in primary sensory neurons in

149 Furthermore, pharmacologic inhibition of eIF2alpha dephosphorylation reduced HSV-1 replication in

150 ion with GSK2606414A led to an inhibition of eIF2alpha phosphorylation, which correlated with reduced

151 sphorylation of eIF2alpha, and inhibition of eIF2alpha signaling activity suppressed CDCA regulation

152 antage to prevent PKR-mediated inhibition of eIF2alpha, which is required for the synthesis of HCV pr

153 reatment of P23H-1 rats with an inhibitor of eIF2alpha phosphatase, salubrinal, led to improved photo

154 optosis inducer, and GADD34, an inhibitor of eIF2alpha phosphorylation, demonstrated that PC1-5TMC in

155 Loss of eIF2alpha-P induced by UVB diminished G1 arrest, DNA rep

156 findings demonstrate that the modulation of eIF2alpha-specific phosphatase cofactor activity can be

157 tegrated stress response, phosphorylation of eIF2alpha (eIF2alpha-P) reduces protein synthesis to con

158 tegrated stress response, phosphorylation of eIF2alpha (eIF2alpha-P) reduces protein synthesis while

159 translation through GCN2 phosphorylation of eIF2alpha (eIF2alpha-P).

160 Increasing phosphorylation of eIF2alpha (p-eIF2alpha) reduces translation rates and sp

161 Increased levels of phosphorylation of eIF2alpha (Ser51) were detected prior to neurodegenerati

162 of the stress response as phosphorylation of eIF2alpha and global protein synthesis returned toward b

163 ional effects elicited by phosphorylation of eIF2alpha and induced no major changes in translation or

164 exposure to H2S leads to phosphorylation of eIF2alpha and inhibition of protein synthesis.

165 unknown function for GCN2 phosphorylation of eIF2alpha and translational control in the formation of

166 raditional model in which phosphorylation of eIF2alpha blocks the regeneration of TC.

167 nvolves regulation of the phosphorylation of eIF2alpha by increased levels of GADD34, a regulatory su

168 Phosphorylation of eIF2alpha controls translation initiation by restricting

169 GADD34:PP1, increases the phosphorylation of eIF2alpha in Schwann cells and largely rescues S63del ne

170 ss response genes and the phosphorylation of eIF2alpha that triggered the assembly of SGs.

171 t PC1 and PC1-5TMC reduce phosphorylation of eIF2alpha through inhibiting PKR phosphorylation.

172 EBP1, as well as elevated phosphorylation of eIF2alpha, an inhibitor of mRNA translation.

173 CDCA increased the phosphorylation of eIF2alpha, and inhibition of eIF2alpha signaling activit

174 chemical that inhibits de-phosphorylation of eIF2alpha, and it can suppress cell death from the ER st

175 t is typically induced by phosphorylation of eIF2alpha, ATF4 translation can be also induced by expre

176 Nonetheless, reducing phosphorylation of eIF2alpha, by Perk haploinsufficiency, also ameliorates

177 ranslation initiation via phosphorylation of eIF2alpha.

178 volved in the H2S-induced phosphorylation of eIF2alpha.

179 deficits independently of phosphorylation of eIF2alpha.

180 through the elevation of phosphorylation of eIF2alpha.

181 l function of IRE1alpha in the regulation of eIF2alpha phosphorylation and the translational control.

182 ene (also known as constitutive repressor of eIF2alpha phosphorylation [CReP]) encoding the regulator

183 ase cofactor CReP (Constitutive Repressor of eIF2alpha Phosphorylation; also known as PPP1R15B).

184 Reversal of eIF2alpha-mediated translational repression using ISRIB

185 ions in the GADD34 uORF affect the status of eIF2alpha-P, translational control, and cell adaptation

186 ant (C127S-PP1c) abrogated the H2S effect on eIF2alpha phosphorylation.

187 d downstream phosphorylation/inactivation or eIF2alpha.

188 oes not induce formation of canonical SGs or eIF2alpha phosphorylation at any time postinfection but

189 e levels of both phospho-PERK (p-PERK) and p-eIF2alpha, and these effects were enhanced upon ER stres

190 s constitutively expressed, controls basal P-eIF2alpha levels in unstressed cells.

191 ng the translational program controlled by p-eIF2alpha enhances auditory imprinting.

192 , cocaine hijacks translational control by p-eIF2alpha, initiating synaptic potentiation and addictio

193 an mRNA whose translation is controlled by p-eIF2alpha-in the VTA also prolongs cocaine-induced LTP.

194 ases, containing GADD34 and CReP, catalyze P-eIF2alpha dephosphorylation.

195 e translation initiation factor eIF2alpha (p-eIF2alpha) accounts for adolescent hypersensitivity to c

196 While phosphorylated eIF2alpha (P-eIF2alpha) attenuates global protein synthesis, mRNAs en

197 the increase of phosphorylated eIF2alpha (p-eIF2alpha) in the cell under ER stress, suppresses the p

198 Increasing phosphorylation of eIF2alpha (p-eIF2alpha) reduces translation rates and spine plasticit

199 th genetic or pharmacological reduction in p-eIF2alpha-mediated translation are more susceptible to n

200 stress signaling associated with increased p-eIF2alpha and ATF4 and decreased sXBP1 and CHOP.

201 ike adults, adolescent mice with increased p-eIF2alpha became more resistant to cocaine's effects.

202 In addition, increased p-eIF2alpha levels impair long-term synaptic plasticity an

203 Trehalose increases pre-stress levels of p-eIF2alpha and its phosphatase subunits and promotes post

204 of ECD led to marked decreases in p-PERK, p-eIF2alpha, and ATF4 levels but robust increases in GRP78

205 S, cytokines, UPR proteins (GRP78, p-PERK, p-eIF2alpha, ATF4 and CHOP) and apoptosis were observed in

206 The impact of eIF2alpha phosphorylation (p-eIF2alpha) on thermal thresholds is dependent on the tra

207 onal control by eIF2alpha phosphorylation (p-eIF2alpha) regulates cocaine-induced LTP in the VTA.

208 adult) mice, a low dose of cocaine reduced p-eIF2alpha in the ventral tegmental area (VTA), potentiat

209 in both mice and humans, and that reduced p-eIF2alpha may enhance susceptibility to nicotine (and ot

210 dolescent mice and adult mice with reduced p-eIF2alpha mediated translation.

211 Here we report that in mice with reduced p-eIF2alpha-mediated translation, cocaine induces persiste

212 Like adolescents, adult mice with reduced p-eIF2alpha-mediated translational control were more susce

213 These findings suggest that p-eIF2alpha regulates synaptic actions of nicotine in both

214 tem Cell, Zismanov et al. (2016) show that P-eIF2alpha, a translational initiation factor, reinforces

215 ct of trehalose on SGs is mediated via the p-eIF2alpha rather than autophagosome pathway.

216 h target eIF2alpha and thereby inhibit the p-eIF2alpha/ATF4/CHOP pro-apoptotic pathway, identifying m

217 n the cell under ER stress, suppresses the p-eIF2alpha/ATF4/CHOP pro-apoptotic pathway.

218 ular stress response pathway, mediated via p-eIF2alpha, represents a mechanism that could be used to

219 -associated proteins, including GRP78, PERK, eIF2alpha, ATF4, IRE1alpha, JNK, p38, and CHOP.

220 m (ER) stress responses by activating a PERK-eIF2alpha signalling axis and Fas-JNK apoptotic pathways

221 tivation of the GCN2-eIF2alpha-ATF4 and PERK-eIF2alpha-ATF4 signaling pathways are responsible for in

222 w that DAP1 is a key regulator, through PERK-eIF2alpha-dependent pathways, of the induction of apopto

223 ER stress as shown by activation of the PERK/eIF2alpha pathway.

224 that Leishmania parasites activate the PERK/eIF2alpha/ATF-4 pathway in cultured macrophages and infe

225 We report here that the PERK/eIF2alpha/ATF4 signaling branch of the integrated endopl

226 ER stress response markers GRP78 and phospho-eIF2alpha, thus suggesting a defect in procollagen proce

227 GADD45, EDEM, ATF4, Hsp90, ATG5, and phospho-eIF2alpha.

228 Mice deficient in phospho-eIF2alpha-mediated translation are impaired in object-pl

229 d compensatory activation of PERK or phospho-eIF2alpha independent upregulation of ATF4 in order to m

230 in response signaling (phospho-PERK, phospho-eIF2alpha, CHOP (CCAAT/enhancer-binding protein homologo

231 Enhancement of the phospho-eIF2alpha adaptation pathway by inhibition of Gadd34-PP1

232 if2s1 locus to encode a non-phosphorylatable eIF2alpha (eIF2alpha(S51A)).

233 rerequisite for its ability to phosphorylate eIF2alpha, is readily induced by JUNV.

234 Enhanced phosphorylated eIF2alpha correlates with high rates of recrudescence fo

235 s latter than the increase of phosphorylated eIF2alpha (p-eIF2alpha) in the cell under ER stress, sup

236 ase caused enhanced levels of phosphorylated eIF2alpha and activating transcription factor (ATF) 4, w

237 hat suppresses the effects of phosphorylated eIF2alpha on mRNA translation, was sufficient to reverse

238 While phosphorylated eIF2alpha (P-eIF2alpha) attenuates global protein synthe

239 CGG and G4C2 repeats trigger phosphorylated-eIF2alpha-dependent stress granule formation and global

240 and oxidative stress, and it phosphorylates eIF2alpha (eIF2alphaP), which inhibits the translation o

241 splicing reaction, while PERK phosphorylates eIF2alpha.

242 attenuates eIF2B activity by phosphorylating eIF2alpha, suggesting that impaired eIF2B activity in ol

243 nuates global translation by phosphorylating eIF2alpha.

244 s pool of activated PKR from phosphorylating eIF2alpha, even following exposure to the synthetic dsRN

245 ce with decreased eIF2alpha phosphorylation (eIF2alpha(+/S51A)) exhibit reduced responses to noxious

246 binding to conserved amino acids in the PKR eIF2alpha binding site and blocking PKR kinase activity.

247 egulated eIF2alpha phosphorylation and a PKR-eIF2alpha pathway in cell apoptosis may be an important

248 inhibits apoptosis of HEK293T cells in a PKR-eIF2alpha-dependent manner, with concurrent up- and down

249 hosphorylation is mediated by the Plasmodium eIF2alpha kinase, PK4.

250 Depletion of PKR prevented eIF2alpha phosphorylation, rescued HCMV replication and

251 deactivates this pathway whereas prolonging eIF2alpha phosphorylation enhances cell survival.

252 f GADD34 to interact with eIF2alpha, promote eIF2alpha dephosphorylation, and suppress PKR toxicity i

253 x virus, and Herpes simplex virus to promote eIF2alpha dephosphorylation.

254 S rRNA, phosphorylated S6 ribosomal protein, eIF2alpha translation factor, and 4EBP1 translation fact

255 Heme-regulated eIF2alpha kinase (HRI) is a key hemoprotein in erythroid

256 ISR) during erythropoiesis by heme-regulated eIF2alpha kinase (HRI).

257 Involvement of PC1-regulated eIF2alpha phosphorylation and a PKR-eIF2alpha pathway in

258 As part of this adaptive response, eIF2alpha-P also induces a feedback mechanism through en

259 animals, the ISR is antagonised by selective eIF2alpha phosphatases comprising a catalytic protein ph

260 ion and phosphorylation of the PKR substrate eIF2alpha and caused a shutoff of host cell protein synt

261 poses the binding site for the PKR substrate eIF2alpha.

262 enabling it to phosphorylate its substrate, eIF2alpha (eukaryotic initiation factor 2alpha), halting

263 ation of the PP1 metal center, that sustains eIF2alpha phosphorylation to protect tissues under stres

264 rrent with reduced global protein synthesis, eIF2alpha-P and the accompanying integrated stress respo

265 educe phosphorylation of PERK and its target eIF2alpha in cells.

266 on of miR-30b-5p and miR-30c-5p which target eIF2alpha and thereby inhibit the p-eIF2alpha/ATF4/CHOP

267 We conclude that eIF2alpha-P is cytoprotective in response to UVB by a me

268 Our findings establish that eIF2alpha phosphorylation regulates not only cell-autono

269 Here we report that eIF2alpha is instrumental in the control of noxious heat

270 Collectively, our findings suggest that eIF2alpha-mediated translational control regulates the p

271 Point mutations altering the eIF2alpha-binding motif impair the ability of GADD34 to

272 howed that this pathway was activated by the eIF2alpha kinase, GCN2, in an apparent deacylated tRNA-i

273 ce parasite glycolysis rates and changes the eIF2alpha phosphorylation pattern as a molecular mechani

274 ystonia, due to rare coding variation in the eIF2alpha effector ATF4.

275 Inhibition of the eIF2alpha holophosphatase GADD34:PP1, increases the phos

276 ble involvement of additional members of the eIF2alpha pathway and identified increased mRNA expressi

277 onia, DYT16, involves a gene upstream of the eIF2alpha pathway, these results mechanistically link mu

278 d skeletal muscle-specific derivative of the eIF2alpha protein kinase R-like ER kinase revealed the e

279 nfection despite continued activation of the eIF2alpha signaling pathway.

280 diated ISR bypassed direct activation of the eIF2alpha stress kinases and instead relied on the inhib

281 Phosphorylation of the eIF2alpha subunit in response to various cellular stress

282 vation of a stress response dependent on the eIF2alpha kinase general control nonderepressible 2 (GCN

283 Interestingly, this eIF2alpha-docking motif is conserved among viral ortholo

284 monstrate that translational control through eIF2alpha phosphorylation is required for normal keratin

285 ) show that translational repression through eIF2alpha phosphorylation mediated by PK4 kinase activit

286 small molecule, renders cells insensitive to eIF2alpha phosphorylation and enhances cognitive functio

287 ripts being either repressed or resistant to eIF2alpha approximately P, whereas a notable cohort of k

288 vent stress granule formation in response to eIF2alpha phosphorylation.

289 thetase gene EPRS is enhanced in response to eIF2alpha-P.

290 quitylation occurs on a timescale similar to eIF2alpha phosphorylation, is dependent upon PERK signal

291 Two eIF2alpha phosphatases, containing GADD34 and CReP, cata

292 sely, uS7-D215 substitutions, perturbing uS7-eIF2alpha interaction in the closed state, confer the op

293 Thus, remodeling of the uS7/eIF2alpha interface appears to stabilize first the open,

294 or the inhibition of eIF2B activity, whereby eIF2alpha phosphorylation destabilizes an autoregulatory

295 s) and eIF2B (GEF and GDF activities), while eIF2alpha phosphorylation in response to diverse signals

296 ession on tumor cells, which correlated with eIF2alpha phosphorylation, positively influenced the cli

297 mpair the ability of GADD34 to interact with eIF2alpha, promote eIF2alpha dephosphorylation, and supp

298 fects against misfolding by interfering with eIF2alpha-P dephosphorylation through selective disrupti

299 nes restore proteostasis by interfering with eIF2alpha-P dephosphorylation.

300 regulatory intramolecular interaction within eIF2alpha; and (ii) the first structural model for the c