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 levels, availability, and phosphorylation therefor

4 eIF4E must be phosphorylated to promote tumor developmen

5 eIF4E RNA-immunoprecipitation sequencing in DLBCL sugges

6 eIF4E stimulates production of enzymes that synthesize t

7 eIF4E, the major cap-binding protein, has long been cons

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

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

10 nitiated by eukaryotic initiation factor 4E (eIF4E) (the m7GTP cap-binding protein), whose binding to

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

12 eukaryotic translation initiation factor 4E (eIF4E) and its isoform, eIF(iso)4E.

13 eukaryotic translation initiation factor 4E (eIF4E) binding proteins (4E-BPs), which are translationa

14 cupancy and eukaryotic initiation factor 4E (eIF4E) binding to the 5' 7mG cap of GW182 mRNA.

15 eukaryotic translation initiation factor 4E (eIF4E) cannot be phosphorylated are resistant to lung me

16 sphorylated eukaryotic initiation factor 4E (eIF4E) have been implicated in many tumor types, and mit

17 ivation of translation initiation factor 4E (eIF4E) is involved in the mechanisms coordinating these

18 Eukaryotic translation initiation factor 4E (eIF4E) is overexpressed early in breast cancers in assoc

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

20 eukaryotic translation initiation factor 4E (eIF4E) with eIF4E-binding protein 1 (4EBP1) was regulate

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

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

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

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

25 form binds translation initiation factor 4E (eIF4E), preventing binding of eIF4G and the recruitment

26 eukaryotic translation initiation factor 4E (eIF4E), which is negatively regulated by eIF4E-binding p

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

28 eukaryotic translation initiation factor 4E (eIF4E), with its inhibitor ribavirin.

29 osphorylate eukaryotic initiation factor 4E (eIF4E)-binding protein (4E-BP1) at authentic sites, gene

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

31 repressor translation initiation factor 4E (eIF4E)-binding protein 1 (4EBP1).

32 tion of the eukaryotic initiation factor 4E (eIF4E)-binding protein 2 gene (Eif4ebp2), encoding the s

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

34 eukaryotic translation initiation factor 4E (eIF4E)-eIF4G interactions and p70 S6 kinase polypeptide

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

36 eukaryotic translation initiation factor 4E (eIF4E)-initiated cap-dependent translation via convergen

37 eukaryotic translation initiation factor 4E (eIF4E).

38 on between eukaryotic initiation factors 4E (eIF4E) and 4G (eIF4G) reduces the enhancement of L-LTP i

39 otic translation initiation factor 4E (4EBP1/eIF4E) cascades.

40 ly suppressed, whereas blockade of the 4EBP1/eIF4E cascade by 4EBP1A4, an unphosphorylatable form of

41 l biogenesis pathway as targets of the 4EBP1/eIF4E cascade in AKT/Ras and Ras/eIF4E livers as well as

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

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

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

45 ction modulates the MAPK pathway to activate eIF4E phosphorylation.

46 lated 4E-BP dissociates from eIF4E, allowing eIF4E to interact with eIF4G and translation initiation

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

48 mRNA however represses its translation in an eIF4E-independent manner, and contributes to silencing o

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

50 d the role of its enrichment in P-bodies and eIF4E-binding in translational regulation in mammalian c

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

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

53 4F, the complex comprising eIF4G, eIF4A, and eIF4E.

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

55 ntration of eIF4F complex subunits eIF4G and eIF4E.

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

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

58 The mTORC1 effectors, RPS6 and eIF4E, play distinct roles and are both necessary for AK

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

60 eral protein synthesis by reducing available eIF4E levels.

61 As a translational coactivator of TGF-beta, eIF4E confers selective mRNA translation, reprogramming

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

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

64 4E-Transporter binds eIF4E via its consensus sequence YXXXXLPhi, shared with

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

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

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

68 esis in a multifaceted manner through 4E-BP1/eIF4E, S6K1 and STAT3.

69 F-A is primarily under the control of 4E-BP1/eIF4E.

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

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

72 ade of the translation initiation complex by eIF4E knockdown or expression of a dominant active 4E-BP

73 global translational control of the host by eIF4E phosphorylation is a key component of the host-pat

74 4E (eIF4E), which is negatively regulated by eIF4E-binding protein 1 (4E-BP1).

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

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

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

78 uring successive pregnancy/lactation cycles, eIF4E overexpression increased self-renewal, triggered D

79 ecruiting the eIF4F complex through a direct eIF4E interaction.

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

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

82 on initiation to yield free subunits (eIF4A, eIF4E, and eIF4G) is presented.

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

84 binding to the cap binding subunit of eIF4F (eIF4E).

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

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

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

88 ion in the absence of the cap-binding factor eIF4E.

89 The translation initiation factor eIF4E is an oncogene that is commonly overexpressed in p

90 Translation initiation factor eIF4E mediates normal cell proliferation, yet induces tu

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

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

93 ibition of the translation initiation factor eIF4E.

94 questering the translation initiation factor eIF4E.

95 es and the key translation initiation factor eIF4E.

96 th eukaryotic translation initiation factor (eIF4E).

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

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

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

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

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

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

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

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

105 Importin 8 only imports cap-free eIF4E.

106 that BDNF induces the release of CYFIP1 from eIF4E, and that this depends on MNK1.

107 -BP1, thus promoting its disassociation from eIF4E.

108 Hyperphosphorylated 4E-BP dissociates from eIF4E, allowing eIF4E to interact with eIF4G and transla

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

110 Furthermore, eIF4E silencing or ribavirin treatment suppressed featur

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

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

113 c hormones stimulate a sustained increase in eIF4E abundance in stem/progenitor cells of lactogenic m

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

115 l apparatus, but only subtle oscillations in eIF4E abundance.

116 adian rhythm blocked diurnal oscillations in eIF4E, 4EBP1, rpS6, Akt, and ERK1/2 phosphorylation and

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

118 ient mouse, we found that a 50% reduction in eIF4E expression, while compatible with normal developme

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

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

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

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

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

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

125 ex vivo approaches, we found that increasing eIF4E levels rescued cells harboring oncogenic c-Myc or

126 s and inactivates 4E-BP1, thereby increasing eIF4E-dependent protein synthesis.

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

128 Our findings indicate eIF4E is maintained at levels in excess for normal devel

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

130 forming growth factor-beta (TGFbeta) induces eIF4E phosphorylation to promote the translation of Snai

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

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

133 Maintaining eIF4E levels below its proneoplastic threshold is an imp

134 Mechanistically, eIF4E silencing or blockade reduced the invasiveness and

135 istinct from those affected by mTOR-mediated eIF4E inhibition.

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

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

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

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

140 eroaryl 13-cis-retinamides that modulate Mnk-eIF4E and AR signaling are discussed.

141 cascades, suggesting that targeting the Mnk/eIF4E axis may provide therapeutic opportunity for the t

142 rful pharmacologic tool in studying the Mnk2/eIF4E-mediated tumorigenic mechanism.

143 A recently discovered small molecule, eIF4E/eIF4G interaction inhibitor 1 (4EGI-1), disrupts t

144 port here a 2.1-A crystal structure of mouse eIF4E in complex with m(7)GTP and with a fragment of hum

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

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

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

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

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

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

151 The oncogenic activity of eIF4E driven by the Mnk kinases is a convergent determin

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

153 hat Hsp90 binds to and maintains activity of eIF4E.

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

155 r memory requires concomitant association of eIF4E to eIF4G as well as S6K1 activity and that the per

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

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

158 anied by increased cap-binding capability of eIF4E and activation of the eIF4E-dependent translationa

159 ntains the alpha+beta fold characteristic of eIF4E proteins and its cap-binding pocket is similarly a

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

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

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

163 particular, we demonstrate that the dose of eIF4E is essential for translating mRNAs that regulate r

164 and revealed a critical role for the dose of eIF4E, specifically in translating a network of mRNAs en

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

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

167 pithelial cells, that elevated expression of eIF4E translationally activates the transforming growth

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

169 tion in vitro and in vivo, is independent of eIF4E, and can drive internal translation initiation.

170 within the leader sequence independently of eIF4E but involves eIF4G.

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

172 ates eIF4A duplex unwinding independently of eIF4E.

173 dingly, rational combinatorial inhibition of eIF4E and Hsp90 inhibitors resulted in cooperative antil

174 Pharmacological inhibition of eIF4E or genetic reduction of neuroligin 1 levels normal

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

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

177 d after reactivation, whereas inhibition of eIF4E-eIF4G interactions did not.

178 nt prototypic inhibitor in the inhibition of eIF4E/eIF4G interaction, thus preventing the eIF4F compl

179 we report that a pharmacologic inhibitor of eIF4E function, ribavirin, safely and potently suppresse

180 initiation is mediated by the interaction of eIF4E with the m(7)GTP cap of mRNA and with eIF4G.

181 eraction is inhibited by the interactions of eIF4E with partner proteins, such as CYFIP1, which acts

182 s indicate that distinct threshold levels of eIF4E govern its biologic output in lactating mammary gl

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

184 Because overexpression of eIF4E is linked to cellular transformation, 4E-BP is a t

185 Overexpression of eIF4E is shown to facilitate the selective translation o

186 Overexpression of eIF4E may be a proinvasive facilitator of TGF-beta activ

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

188 asis of CRC cells, whereas overexpression of eIF4E or knockdown of 4E-BP1 had the opposite effect and

189 rmore, we demonstrate that overexpression of eIF4E, the proto-oncogene whose activity is specifically

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

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

192 The phosphorylation of eIF4E is essential for oncogenic transformation but is o

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

194 Phosphorylation of eIF4E specifically promoted translation of Period 1 (Per

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

196 ty and also blocking MNK1 phosphorylation of eIF4E.

197 te strongly increased MNK phosphorylation of eIF4E.

198 e 4EGI-1 attaches to a hydrophobic pocket of eIF4E between beta-sheet2 (L60-T68) and alpha-helix1 (E6

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

200 mains to be understood regarding the role of eIF4E in human cancer.

201 However, the role of eIF4E phosphorylation in metastasis is not known.

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

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

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

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

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

207 ranslation globally in a manner dependent on eIF4E binding its consensus Y30X4L site.

208 ors to kill these cancers through effects on eIF4E.

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

210 acts allosterically by binding to a site on eIF4E distant from the eIF4G binding epitope.

211 re the only known kinases that phosphorylate eIF4E at Ser209.

212 Furthermore, phosphorylated eIF4E relocates to the polysomes, and this contributes t

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

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

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

216 nctionally distinct from the canonical plant eIF4E involved in translation initiation.

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

218 o phosphorylation of the cap-binding protein eIF4E in the mouse suprachiasmatic nucleus of the hypoth

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

220 The messenger RNA (mRNA) cap-binding protein eIF4E is an oncoprotein that has an important role in ca

221 ction of 4E-BP1 with the cap-binding protein eIF4E regulates protein expression by controlling the se

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

223 ) and phosphorylates the cap-binding protein eIF4E.

224 f the 4EBP1/eIF4E cascade in AKT/Ras and Ras/eIF4E livers as well as in human HCC cell lines and tiss

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

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

227 ibition of protein synthesis by up-regulated eIF4E-binding protein 1.

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

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

230 or mTOR downstream effector, which represses eIF4E activity and cap-dependent translation, leads to m

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

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

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

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

235 ts cap-dependent translation by sequestering eIF4E.

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

237 Strikingly, eIF4E inhibition alone repressed HA levels as effectivel

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

239 Mnk1/2 degradation to substantially suppress eIF4E phosphorylation.

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

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

242 output in lactating mammary glands and that eIF4E overexpression in the context of stem/progenitor c

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

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

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

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

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

248 The eIF4E-binding protein (4E-BP) is a phosphorylation-depen

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

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

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

252 e 4E-BP fragments bound to eIF4E contain the eIF4E consensus binding motif, (54)YXXXXLPhi(60) (motif

253 In contrast, the eIF4E-directed protein synthesis pathway alone cannot su

254 teraction inhibitor 1 (4EGI-1), disrupts the eIF4E/eIF4G interaction and promotes binding of 4E-BP1 t

255 However, the eIF4E dose requirement at an organismal level remains un

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

257 or efforts to pharmacologically modulate the eIF4E-cap interaction as a means to inhibit pathological

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

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

260 ng capability of eIF4E and activation of the eIF4E-dependent translational apparatus, but only subtle

261 4Ei-1, a specific chemical antagonist of the eIF4E-mRNA cap interaction, potently inhibits transformi

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

263 Here, we show that the eIF4E/eIF4G inhibitor 4EGI-1 acts allosterically by bind

264 eIF4G binding to the eIF4E-m(7)GTP cap complex is resistant to mTOR inhibitio

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

266 cap-dependent, a result confirmed using the eIF4E/4G inhibitor drug 4E1RCat.

267 translation repressor complex along with the eIF4E-binding protein 4E-Transporter, the Xp54/DDX6 RNA

268 ical TGFbeta signaling branch acting through eIF4E phosphorylation.

269 The binding of 4E-BP1 and 4EGI-1 to eIF4E is therefore not mutually exclusive, and both liga

270 lation, thereby increasing 4E-BP1 binding to eIF4E and inhibiting mRNA translation.

271 to promote both increased 4E-BP1 binding to eIF4E and VEGF expression.

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

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

274 RC1 signaling and enhanced 4E-BP1 binding to eIF4E.

275 bition by RAD001, increased 4EBP1 binding to eIF4E.

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

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

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

279 f 14- to 16-residue 4E-BP fragments bound to eIF4E contain the eIF4E consensus binding motif, (54)YXX

280 nteraction and promotes binding of 4E-BP1 to eIF4E.

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

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

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

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

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

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

287 Noise is not increased when eIF4E is overproduced.

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

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

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

291 The mechanisms by which eIF4E directs such distinct biologic outputs remain unkn

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

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

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

295 ation in vitro at a lower rate compared with eIF4E.

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

297 bind eIF4G in vivo when in competition with eIF4E.

298 ranslation initiation factor 4E (eIF4E) with eIF4E-binding protein 1 (4EBP1) was regulated by the mTO

299 ith DcpS but stabilized the interaction with eIF4E.

300 rin, currently being tested in patients with eIF4E-overexpressing leukemia, as a strategy to treat so