ライフサイエンスコーパス: eIF4E

1 eIF4E binding to eIF4G601-1196 induced a conformational

2 eIF4E drives nuclear export and translation of BCL6, MYC

3 eIF4E is a notoriously challenging target, and most of t

4 eIF4E levels, availability, and phosphorylation therefor

5 eIF4E RNA-immunoprecipitation sequencing in DLBCL sugges

6 eIF4E stimulates production of enzymes that synthesize t

7 eIF4E's association with noncoding RNAs strongly positio

8 of mammalian target of rapamycin complex 1 (eIF4E-dependent) or hypoxia-inducible factor 2alpha expr

9 his to ~60 to 100%, depending on the RNA; 2) eIF4E physically associates with noncoding RNAs in the n

10 Our findings demonstrate that the MNK1/2-eIF4E signaling axis is an important contributing factor

11 eukaryotic translation initiation factor 4E (eIF4E) activation.

12 ulation of translation initiation factor 4E (eIF4E) activity occurs in various cancers.

13 epletion of eukaryotic initiation factor 4E (eIF4E) and phosphorylation of eukaryotic initiation fact

14 Eukaryotic translation initiation factor 4E (eIF4E) binds the m7GTP cap structure at the 5'-end of mR

15 eukaryotic translation initiation factor 4E (eIF4E) binds the MTE despite the absence of an m(7)GpppN

16 eukaryotic translation initiation factor 4E (eIF4E) from binding to p53 mRNA.

17 suppressed eukaryotic initiation factor 4E (eIF4E) phosphorylation, while the use of antiandrogens r

18 Eukaryotic translation initiation factor 4E (eIF4E) selectively promotes translation of mRNAs with at

19 eukaryotic translation initiation factor 4E (eIF4E) with eIF4G is a key control step in eukaryotic tr

20 eukaryotic translation initiation factor 4E (eIF4E), a prooncogenic protein highly elevated in many c

21 itor of the eukaryotic initiation factor 4E (eIF4E), an enzyme involved in mRNA recognition.

22 n cap-bound eukaryotic initiation factor 4E (eIF4E), eIF4G, and poly(A) tail-binding protein (PABP) t

23 eukaryotic translation initiation factor 4E (eIF4E), itself a cap-binding protein, drives the express

24 eukaryotic translation initiation factor 4E (eIF4E), resulting in enhanced translation of activating

25 eukaryotic translation initiation factor 4E (eIF4E), with CCl2-substituted analogues having the highe

26 Eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1) inhibits cap-dependent

27 eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1), leading to suppressio

28 ediated by translation initiation factor 4E (eIF4E)-binding proteins (4E-BPs).

29 ugh the cap-eukaryotic initiation factor 4E (eIF4E)-eIF4G-eIF3-40S chain of interactions, but the mec

30 translation of carboxypeptidase E in a 4EBP2/eIF4E-dependent manner.

31 n its regulation and position the importin 8-eIF4E complex as a novel therapeutic target.

32 A helicase, eIF4A, independently accelerated eIF4E-cap association.

33 Accordingly, eIF4E was required for survival of DLBCL including the m

34 In the near absence of mTOR, CDK1 activates eIF4E-dependent translation in MPs through phosphorylati

35 Surprisingly, we identify Hsp70 mRNA as an eIF4E target.

36 E-BP2:eIF4E binding, shifting 4E-BP2 into an eIF4E binding-incompatible conformation and regulating t

37 tly capped at steady state (~30 to 50%), and eIF4E overexpression increased this to ~60 to 100%, depe

38 ment of 19F NMR assays for DcpS activity and eIF4E binding.

39 tracellular signal-regulated kinase axis and eIF4E impaired 5'-cap-dependent translation and abrogate

40 imity ligation assays for phospho-4E-BP1 and eIF4E revealed different in situ interactions during int

41 AUG-initiated translation, is m(7)G cap and eIF4E dependent, requires the eIF4A helicase, and is str

42 ignaling pathway, including mTOR, eIF4A, and eIF4E, are downregulated by mf, suggesting that mf targe

43 4F, the complex comprising eIF4G, eIF4A, and eIF4E.

44 These findings link changes in eIF4B and eIF4E to SG induction in regions vulnerable to death aft

45 ntration of eIF4F complex subunits eIF4G and eIF4E.

46 three initiation factors, eIF4A, eIF4G, and eIF4E, by the chemical inhibitor 4E1RCat did not impact

47 important, as we show for sites on H2A1 and eIF4E.

48 g to the binding interface between Rbm38 and eIF4E, including an 8 amino acid peptide (Pep8) derived

49 As eIF4E levels were reduced, we determined its binding to

50 eral protein synthesis by reducing available eIF4E levels.

51 We observed that 4E-BP1 and eIF4G bind eIF4E at similar levels during interphase and mitosis.

52 Here we show that the cap-binding eIF4E-homologous protein 4EHP is an integral component o

53 and eukaryotic initiation factor 4E-binding (eIF4E-binding) protein 1 (4E-BP1), and mTORC2 modulates

54 4E-Transporter binds eIF4E via its consensus sequence YXXXXLPhi, shared with

55 dies show that merestinib effectively blocks eIF4E phosphorylation in AML cells and suppresses primit

56 Consistently, EG5 directly bound eIF4E in a similar manner to VPg, demonstrating that thi

57 t of enhanced activation of the mTORC1-4E-BP-eIF4E axis, secondary to aberrant assembly of a raptor-p

58 cordingly, interfering with the mTORC1/4E-BP/eIF4E axis inhibited the growth potential endowed by acc

59 nslation in initiation factor 4E) by 4E-BP1 (eIF4E-binding protein 1) and enhanced cap-independent Cd

60 ed with decreased phosphorylation of 4E-BP1 (eIF4E-binding protein 1), a protein that binds to eIF4E

61 I expression via the mTORC1-dependent 4E-BP1/eIF4E pathway.

62 s, size and autophagy, whereas mTORC1/4E-BP2-eIF4E pathway regulates beta-cell proliferation.

63 xchange leads to graded inhibition of 4E-BP2:eIF4E binding, shifting 4E-BP2 into an eIF4E binding-inc

64 of 4E-BP1 phosphorylation, and attenuated by eIF4E expression.

65 with its increased translation regulated by eIF4E, contributes to tamoxifen resistance.

66 , levels of capping RNAs can be regulated by eIF4E.

67 V IRES-mediated translation is stimulated by eIF4E availability in nuclease-treated cell-free extract

68 domain, partially sequestering the canonical eIF4E-binding helix.

69 of its translation to reduction in cellular eIF4E concentrations.

70 the associations of the core mRNP components eIF4E, eIF4G, and PABP and of the decay factor DDX6 in h

71 sensitivity element (CapSE) which conferred eIF4E-dependent capping sensitivity.

72 Polysome fractionation experiments confirmed eIF4E could modulate the translation of ERalpha and FOXM

73 n of eIF4E-eIF4G-eIF3 interactions converted eIF4E into a specific inhibitor of initiation on capped

74 which to our knowledge is the first covalent eIF4E inhibitor with cellular activity.

75 signal-regulated kinase signaling decreased eIF4E and phosphorylated eIF4E accumulation and signific

76 mportance of these interactions, and of Ded1-eIF4E association, in vivo were poorly understood.

77 Phosphorylation of intrinsically disordered eIF4E binding proteins (4E-BPs) regulates cap-dependent

78 ansporter NES binding weaker to CRM1(E571K), eIF4E-transporter was mislocalized in tumor cells carryi

79 MNKs), which converge on the mTORC1 effector eIF4E, are therapeutic targets in NF1-deficient malignan

80 rotein T-cell internal antigen-1 with eIF3b, eIF4E, and ribosomal protein S6 and studied eIF2 and eIF

81 Ablating Ded1 interactions with eIF4A/eIF4E unveiled a requirement for the Ded1-CTD for robust

82 ion but both can interact with eIF4A, eIF4B, eIF4E isoforms, and the poly(A)-binding protein.

83 formed trimeric complexes with eIF4E-eIF4G, eIF4E bound VPg-luciferase RNA conjugates, and these VPg

84 slation initiation as part of the PABP-eIF4G-eIF4E complex that stimulates the initial cap-binding st

85 t, implicating an unexplored role for eIF4G1/eIF4E in insulin biosynthesis.

86 umulates in the nucleus, leading to elevated eIF4E-dependent mRNA export.

87 that VPg-RNA conjugates functionally engage eIF4E.

88 omplex proteins was associated with enhanced eIF4E translation targets cyclin D1 and c-Myc.

89 Before entering, eIF4E likely dissociates from the cap to overcome steric

90 the eukaryotic translation initiation factor eIF4E and associate with the translation machinery acros

91 alization of a translation initiation factor eIF4E and by ribosome-bound nascent chain ribopuromycyla

92 rexpression of translation initiation factor eIF4E to increase protein synthesis in specific brain ce

93 actions of the translation initiation factor eIF4E with the universal mRNA 5' cap structure, dominate

94 the eukaryotic translation initiation factor eIF4E, an oncoprotein, drives HA biosynthesis.

95 n2, the 4E-BP (translation initiation factor eIF4E-binding protein) translation repressor protein Caf

96 es and the key translation initiation factor eIF4E.

97 ibition of the translation initiation factor eIF4E.

98 granules that contain the translation factor eIF4E.

99 in eukaryotic translation initiation factor (eIF4E) is enhanced.

100 levels of the eukaryotic initiation factor, eIF4E, a potent oncogene.

101 usurp a host translation initiation factor, eIF4E, in a way that differs from host mRNA interactions

102 G cap-binding translation initiation factor, eIF4E, respectively.

103 he binding of translation initiation factors eIF4E and eIF4G to p63alpha mRNA.

104 Translation factors eIF4E and eIF4G form eIF4F, which interacts with the mes

105 abundance of the other cap-complex factors, eIF4E and eIF4A.

106 t eukaryotic translation initiation factors, eIF4E and eIF4G or their isoforms.

107 a melon eIF4G peptide and propose the first eIF4E-eIF4G structural model for plants.

108 First, eIF4E binding to eIF4G generates a high-affinity binding

109 BTE-binding region, and binding domains for eIF4E, eIF4A, and eIF4B; (ii) eIF4G601-1488, which conta

110 ning their ability to compete with eIF4G for eIF4E binding within the translation initiation complex.

111 Both use an alpha-helical motif for eIF4E binding, warranting the investigation of stapled p

112 ap structure, which is normally required for eIF4E to bind RNA.

113 Surface-associated HA was required for eIF4E's oncogenic activities suggesting that eIF4E poten

114 Importin 8 only imports cap-free eIF4E.

115 excitability were attenuated in neurons from eIF4E(S209A) mice.

116 ry breast cancer samples confirmed that high eIF4E expression was significantly associated with incre

117 d elevated capping for specific RNAs in high-eIF4E leukemia specimens, supporting a role for cap dysr

118 ally, HA was retained on the surface of high-eIF4E cells, rather than being extruded into the extrace

119 genomic RNA (gRNA) and associates with host eIF4E for successful infection.

120 importin 8 as a factor that directly imports eIF4E into the nucleus.

121 In eIF4E overexpressing breast cancer, the increased ERalph

122 n Pep8 forms a hydrogen bond with Asp-202 in eIF4E.

123 -treatment is associated with an increase in eIF4E(S209) phosphorylation.

124 hat target a noncatalytic lysine (Lys162) in eIF4E.

125 ced by peripheral nerve injury is reduced in eIF4E(S209A) and Mnk1/2(-/-) mice and following cercospo

126 roviding a new tool for acutely inactivating eIF4E in cells, our computational approach may offer a g

127 antagonists including bicalutamide increased eIF4E phosphorylation that induced resistance to combina

128 sociation of PTC-containing mRNAs, increased eIF4E-bound PTC-containing mRNA levels, and subsequent e

129 prostatectomy samples showed that increased eIF4E phosphorylation strongly correlated with the cell

130 in vitro models, and revealed that increased eIF4E(S209) phosphorylation is associated with resistanc

131 NK1a kinase, which correlates with increased eIF4E phosphorylation in vitro and in vivo.

132 ts who have AML is correlated with increased eIF4E-dependent export of transcripts encoding oncoprote

133 Indeed, eIF4E inhibition induces tumor regression in cell line a

134 was conferred by phosphorylation independent eIF4E overexpression.

135 echanism whereby phosphorylation independent eIF4E translational reprogramming in governing the prote

136 This difference indicates eIF4E may be a soft target for engineering of-or breedin

137 tion required the suppression of MNK-induced eIF4E phosphorylation and was not recapitulated by suppr

138 In human cells, VPg inhibited eIF4E-dependent RNA export, translation, and oncogenic t

139 his resistance can be overcome by inhibiting eIF4E phosphorylation with Mnk1/2 or ERK1/2 inhibitors.

140 by a potent, clinical compound that inhibits eIF4E phosphorylation, eFT508, which reverses the aggres

141 rovides a unique model system to interrogate eIF4E.

142 ternary initiation factor complex involving eIF4E, eIF4G, and eIF4A1.

143 reduced hyperalgesic priming in mice lacking eIF4E phosphorylation (eIF4E(S209A) ).

144 n of stapled peptide mimics for manipulating eIF4E PPIs.

145 Rather, type I IFNs stimulate MNK-mediated eIF4E phosphorylation in DRG neurons to promote pain hyp

146 bind the two CRM1 similarly, NESs from Mek1, eIF4E-transporter, and RPS2 showed >10-fold affinity dif

147 resolution structure of melon (Cucumis melo) eIF4E in complex with a melon eIF4G peptide and propose

148 As in the case of metazoan eIF4E-eIF4G, this may have very important practical impl

149 d noncanonical motifs, similarly to metazoan eIF4E-eIF4G complexes.

150 anonical alpha-helical motif, while metazoan eIF4E-binding proteins (m4E-BPs) advantageously compete

151 Although microglial eIF4E overexpression elevates translation in both sexes,

152 anipulations and pharmacology to inhibit MNK-eIF4E activity in animals with spared nerve injury, a mo

153 sitivity that is blunted in mice lacking MNK-eIF4E signaling.

154 harmacological and genetic inhibition of MNK-eIF4E signaling completely blocked and reversed maladapt

155 ns act via a specific signaling pathway (MNK-eIF4E signaling), which is known to produce nociceptor s

156 ic and pharmacological inhibition of the MNK-eIF4E signaling axis protected against and reversed spon

157 s sustained mTORC1 activation driven by MNK1-eIF4E signaling.

158 ity, is identified as a novel target of MNK1-eIF4E signaling.

159 ropathic pain pointing to a key role of MNK1-eIF4E-mediated translation of a complex of mRNAs that co

160 Our work strongly suggests that MNK1-eIF4E signaling drives CIPN and that a drug in human cli

161 on regulation signaling circuit wherein MNK1-eIF4E activity drives mTORC1 via control of RagA transla

162 onments can explain why they encode multiple eIF4E (LeishIF4Es) and eIF4G (LeishIF4Gs) paralogs, as e

163 The IRES was dependent on eIF4G, but not eIF4E, for activity.

164 on sequencing in DLBCL suggests that nuclear eIF4E controls an extended program that includes B-cell

165 The ability of eIF4E to recognize the cap is prevented by its binding t

166 e strongly attenuated by genetic ablation of eIF4E phosphorylation, MNK1 elimination or treatment wit

167 of TOP mRNAs, effectively impeding access of eIF4E to the cap and preventing eIF4F assembly.

168 Nuclear accumulation of eIF4E in patients who have AML is correlated with increa

169 K2) play a fundamental role in activation of eIF4E.

170 The oxygen-dependent activities of eIF4E and eIF4E2 are elucidated by observing their polys

171 s important for the prooncogenic activity of eIF4E, at least in this context.

172 hat Hsp90 binds to and maintains activity of eIF4E.

173 lular delivery of a nucleotide antagonist of eIF4E in mantle cell lymphoma (MCL) cells.

174 CGP and eIF4G(1357-1600) decrease binding of eIF4E to eIF4G.

175 lational control and requires the binding of eIF4E to the 5' cap of mRNA.

176 slational 'closed loop' complex comprised of eIF4E, eIF4G, and Pab1, and depletion of eIF4G mimics th

177 interfering RNA-mediated knockdown (k/d) of eIF4E-sensitized CRPC cells to RAD001+bicalutamide, wher

178 small interfering RNA-mediated depletion of eIF4E in human SCC cells (A431 and SCC-13) reduced eIF4G

179 Omission of eIF4A or disruption of eIF4E-eIF4G-eIF3 interactions converted eIF4E into a spe

180 ented modality for control and engagement of eIF4E and show that VPg-RNA conjugates functionally enga

181 alogs or ribavirin prevents nuclear entry of eIF4E, which mirrors the trafficking phenotypes observed

182 wn to be mediated by increased expression of eIF4E and its increased availability by hyperactive mTOR

183 trypanosomatid N-terminally extended form of eIF4E acts as the core molecular scaffold for the mRNA-c

184 in the nucleus; and 3) approximately half of eIF4E-capping targets identified are noncoding RNAs.

185 pendent translation mediated by a homolog of eIF4E, eIF4E2.

186 in the presence of the PIC, independently of eIF4E*eIF4G, but dependent on subunits i and g of the he

187 ates eIF4A duplex unwinding independently of eIF4E.

188 Inhibition of eIF4E phosphorylation by treatment with CGP57380 (an inh

189 iles and show potent on target inhibition of eIF4E phosphorylation in cells.

190 constructs was not affected by inhibition of eIF4E-dependent translation and such expression was depe

191 ng the eIF4E with an allosteric inhibitor of eIF4E and eIF4G binding, 4EGI-1, decreased the eIF4E/eIF

192 Here, we investigated the interaction of eIF4E with 4E-BP1 or eIF4G during interphase and mitosis

193 The subcellular localization of eIF4E closely correlates with patients' responses.

194 uced insulin content associated with loss of eIF4E, the mRNA 5' cap-binding protein of the initiation

195 uced insulin content associated with loss of eIF4E, the mRNA 5'-cap binding protein of the initiation

196 ervations proposed either an unknown mode of eIF4E engagement or a competition of VPg for the m(7)G c

197 icity of TC was rescued by overexpression of eIF4E or c-Myc.

198 and 2 inhibitors prevent phosphorylation of eIF4E and eliminate the self-renewal capacity of LSCs.

199 ctive mTOR and to require phosphorylation of eIF4E at Ser209 by increased MNK activity.

200 Inhibiting Mnk1/2-induced phosphorylation of eIF4E may represent a unique approach for the treatment

201 Cbz-B3A inhibits the phosphorylation of eIF4E-binding protein 1 (4EBP1) and blocks 68% of transl

202 ty and also blocking MNK1 phosphorylation of eIF4E.

203 te strongly increased MNK phosphorylation of eIF4E.

204 Genetic reconstitution of eIF4E in single beta-cells or intact islets of betaeIF4G

205 of and parallel to Atf4 in the regulation of eIF4E-binding protein 1 (4ebp1), a mammalian target of r

206 VPg directly bound the cap-binding site of eIF4E and competed for m(7)G cap analog binding.

207 The crystal structure of eIF4E in complex with the CCl2-analogue revealed a signi

208 Cap-dependent changes to the structure of eIF4E underpin this selectivity.

209 es that eIF4G binds to the dorsal surface of eIF4E through a single canonical alpha-helical motif, wh

210 Examination of downstream targets of eIF4E-mediated translation, including survivin, demonstr

211 ese findings position nuclear trafficking of eIF4E as a critical step in its regulation and position

212 on of a hypophosphorylated mutant version of eIF4E-binding protein (4EBP1) resulted in decreased expr

213 ors to kill these cancers through effects on eIF4E.

214 Phosphorylation of ser209 on eIF4E regulates the translation of a subset of mRNAs.

215 he Ded1-NTD required for binding to eIF4A or eIF4E in vitro.

216 mpairs native Ded1 association with eIF4A or eIF4E, and reduces cell growth, polysome assembly, and t

217 signaling decreased eIF4E and phosphorylated eIF4E accumulation and significantly diminished cell-cyc

218 ected increased expression of phosphorylated eIF4E, eIF4G, and eIF4A1 in human and murine skin SCCs.

219 iming in mice lacking eIF4E phosphorylation (eIF4E(S209A) ).

220 hich eIF4E-eIF4G-eIF3-40S interactions place eIF4E at the leading edge of the 40S subunit, and mRNA i

221 y important practical implications, as plant eIF4E-eIF4G is also involved in a significant number of

222 ted sequestration of the cap-binding protein eIF4E (eukaryotic translation in initiation factor 4E) b

223 hosphorylation of the 5' cap-binding protein eIF4E by its specific kinase MAPK interacting kinases (M

224 orylation site on the 5' cap-binding protein eIF4E is a critical mechanism for changes in nociceptor

225 of eIF4F compounds, the cap-binding protein eIF4E, and eIF4B, suggesting that remodeling of the eIF4

226 ylation target, the mRNA cap binding protein eIF4E, attenuates many types of nociceptive plasticity i

227 ) and phosphorylates the cap-binding protein eIF4E.

228 ether, we conclude that modulating the Rbm38-eIF4E complex may be explored as a therapeutic strategy

229 Disruption of the Rbm38-eIF4E complex via synthetic peptides induces wild-type p

230 ced the ability of Pep8 to inhibit the Rbm38-eIF4E complex.

231 ents binding of MNK to intact eIF4G, reduces eIF4E phosphorylation and inhibits translation of only c

232 on to tamoxifen is restored only by reducing eIF4E expression or mTOR activity and also blocking MNK1

233 At relapse, eIF4E reaccumulates in the nucleus, leading to elevated

234 gen depletion (hypoxia), human cells repress eIF4E and switch to an alternative cap-dependent transla

235 y, the hepatitis A virus (HAV) IRES requires eIF4E for its translation, but no mechanism has been pro

236 decreased the formation of SGs and restored eIF4E and eIF4B levels in CA1.

237 riptome and translatome analysis we revealed eIF4E overexpression could promote cellular activities m

238 onses to the m(7)G-cap competitor ribavirin, eIF4E is mainly cytoplasmic.

239 Second, eIF4E binding to eIF4G strongly stimulates the rate of d

240 fter phosphorylation, contains the secondary eIF4E-binding site and three other phospho-sites, whose

241 ts cap-dependent translation by sequestering eIF4E.

242 E-BP1 variant that constitutively sequesters eIF4E promoted reporter activity.

243 ce and selectively normalizes ERK signaling, eIF4E phosphorylation and the expression of MMP-9.

244 Strikingly, eIF4E inhibition alone repressed HA levels as effectivel

245 d PTC-containing mRNA levels, and subsequent eIF4E-dependent translation.

246 dynamics of Syp and the number of msp300:Syp:eIF4E RNP granules at the synapse, suggesting that these

247 east in part through interactions with 4E-T (eIF4E transporter) protein, but the precise mechanism is

248 nly clinically approved drug known to target eIF4E, is an anti-viral molecule currently used in hepat

249 Here we demonstrate that eIF4E regulates HAV IRES-mediated translation by two dis

250 ation, including survivin, demonstrated that eIF4E(S209) phosphorylation increased cap-independent tr

251 Our data also reveal that eIF4E promotes eIF4F binding and increases the rate of r

252 n and purified virion RNA, we also show that eIF4E promotes the rate of eIF4G cleavage by the 2A prot

253 eIF4E's oncogenic activities suggesting that eIF4E potentiates an oncogenic HA program.

254 The eIF4E:eIF4G interaction was not inhibited but rather inc

255 AP kinase-interacting kinase 1 (Mnk1/2), the eIF4E upstream kinase) or inhibitors of extracellular si

256 of regulation of the interaction between the eIF4E/eIF4G subunits of the translation initiation facto

257 es at 5'-terminal AUGs was stimulated by the eIF4E-cap interaction and followed "the first AUG" rule,

258 F4E and eIF4G binding, 4EGI-1, decreased the eIF4E/eIF4G expression and reduced the proliferation.

259 Furthermore, disrupting the eIF4E with an allosteric inhibitor of eIF4E and eIF4G bi

260 in; and (iii) eIF4G742-1196, which lacks the eIF4E-binding site.

261 As there are no cysteines near the eIF4E cap binding site, we developed a covalent docking

262 motif and a second noncanonical motif of the eIF4E surface.

263 death, potentially through modulation of the eIF4E, EZH2 and ERK pathways.

264 identity of the phosphorylation marks on the eIF4E-bound 4E-BP1 isoforms and uncovered a population o

265 The paradigm on the eIF4E-eIF4G interaction states that eIF4G binds to the d

266 by post-translationally down-regulating the eIF4E inhibitory protein 4E-BP1.

267 Surprisingly, we found that the eIF4E-binding domain of eIF4GI increases not only the bi

268 where three 3'CITEs enhance translation: the eIF4E-binding Panicum mosaic virus-like translational en

269 rmational equilibrium, controlling access to eIF4E binding sites.

270 gnize the cap is prevented by its binding to eIF4E binding protein (4E-BP), which thereby inhibits ca

271 rsal eukaryotic bipartite mode of binding to eIF4E is proposed.

272 -binding protein 1), a protein that binds to eIF4E (eukaryotic translation initiation factor 4E) and

273 alyses demonstrate that plant eIF4G binds to eIF4E through both the canonical and noncanonical motifs

274 The modified RNA binds to eIF4E, demonstrating the utility of this labelling techn

275 The inhibitor 4EGI-1 binds to eIF4E, thereby preventing association with eIF4G through

276 ted at Thr-70, Ser-83, and Ser-101, bound to eIF4E during mitosis.

277 ecific mode of binding, in stark contrast to eIF4E.

278 d in untreated patients with AML, leading to eIF4E nuclear accumulation.

279 cy and was associated with a lower 4E-BP1-to-eIF4E ratio.

280 tic mice, the repressor of mRNA translation, eIF4E-binding protein 1 (4E-BP1), is O-GlcNAcylated, and

281 Typically, eIF4E is localized to both the nucleus and cytoplasm, wh

282 , our data reveal how picornavirus IRESs use eIF4E-dependent and -independent mechanisms to promote t

283 ng both a cap and 5'-terminal RNA duplex via eIF4E phosphorylation, thereby enhancing the coupled cap

284 nsional (3D) fold, and characterized the VPg-eIF4E complex using NMR and biophysical techniques.

285 In this way, eIF4E inhibition can overcome drug resistance to Hsp90 i

286 Noise is not increased when eIF4E is overproduced.

287 We have identified oxygen conditions where eIF4E is the dominant cap-binding protein (21% normoxia

288 d CRPC cells to RAD001+bicalutamide, whereas eIF4E overexpression induced resistance.

289 (to mimic tumor microenvironments), whereas eIF4E mediates cap-dependent translation at 21% oxygen (

290 sults are consistent with the model in which eIF4E-eIF4G-eIF3-40S interactions place eIF4E at the lea

291 Whilst eIF4E overexpression could enhance the translation of bo

292 lexes, the cap was no longer associated with eIF4E.

293 we have assessed how mRNA associations with eIF4E, eIF4G1 and eIF4G2 change globally in response to

294 Our results show that 4EHP competes with eIF4E for binding to 4E-T, and this interaction increase

295 Moreover, VPg formed trimeric complexes with eIF4E-eIF4G, eIF4E bound VPg-luciferase RNA conjugates,

296 Consistent with eIF4E-transporter NES binding weaker to CRM1(E571K), eIF

297 Coupled with eIF4E translational regulation, our study highlights an

298 4E-BP1 isoform (delta) did not interact with eIF4E, whereas a distinct 4E-BP1 phospho-isoform, EB-gam

299 competing with eIF4G for an interaction with eIF4E.

300 4E-BP1 isoforms and their interactions with eIF4E throughout the cell cycle and indicate that 4E-BP1

301 by independent interactions of its NTD with eIF4E and eIF4A, and its CTD with eIF4G.