ライフサイエンスコーパス: eIF-4E

1 eIF-4E is involved in nucleocytoplasmic transport of spe

2 eIF-4E overexpression has been demonstrated in human tum

3 eIF-4E overexpression leads to increased cyclin D1 prote

4 eIF-4E was over expressed in malignant cholangiocytes.

5 apamycin-induced dephosphorylation of 4BP-1, eIF-4E-eIF-4G complexes (eIF-4F) were still detected.

6 rylation of eukaryotic initiation factor 4E (eIF-4E) (cap-binding protein) and its physical sequestra

7 n proteins, eukaryotic initiation factor 4E (eIF-4E) and 4E-binding protein (4E-BP1), a suppressor of

8 eukaryotic translation initiation factor 4E (eIF-4E) to the inhibitory protein 4BP-1 blocks translati

9 rylation of eukaryotic initiation factor 4E (eIF-4E), c-Jun N-terminal kinase (JNK) and ceramide-acti

10 The eukaryotic initiation factor 4E (eIF-4E)-binding proteins PHAS-I and PHAS-II were found t

11 eukaryotic translation initiation factor 4E (eIF-4E).

12 tion of the eukaryotic initiation factor-4E (eIF-4E) binding protein, PHAS-1, in activated T lymphocy

13 on from the eukaryotic initiation factor-4E (eIF-4E) complex.

14 inds to the eukaryotic initiation factor-4E (eIF-4E), preventing formation of a functional eIF-4F com

15 substrate, eukaryotic initiation factor-4E (eIF-4E).

16 The isoelectric states of eIF-4B, eIF-4F (eIF-4E, p26), eIF-iso4F (eIF-iso4E, p28), and eIF-2alpha

17 lting in suppression of MAP kinase activity, eIF-4E and 4E-BP1 phosphorylation, and eIF-4E/4E-BP1 dis

18 whether growth factor treatment could alter eIF-4E or 4E-BP1 phosphorylation state in MO7e cells.

19 Although eIF-4E regulates the recruitment of mRNA to ribosomes, a

20 ion, these results demonstrate that BP-1 and eIF-4E can act either in concert or in opposition to ind

21 BP-1 and eIF-4E can therefore act on cap-dependent translation in

22 sphorylation, and for both p70 S6 kinase and eIF-4E BP1, such protection requires that the rapamycin-

23 gulatory proteins 4E-BP1, p70 S6 kinase, and eIF-4E, thus providing a mechanism for the modulation of

24 The selective inhibition of p70 and eIF-4E BP1 phosphorylation by amino acid withdrawal rese

25 hosphorylation and responsiveness of p70 and eIF-4E BP1 to insulin.

26 vity, eIF-4E and 4E-BP1 phosphorylation, and eIF-4E/4E-BP1 dissociation.

27 initiation via p70 S6 kinase (p70(s6k)) and eIF-4E binding protein 1 (4E-BP1).

28 ion rapalogs and is mediated by a TORC1- and eIF-4E-dependent mechanism ultimately signaling to RAF.

29 Conversely, blocking eIF-4E function by expression of antisense RNA, or overe

30 ase activity and the phosphorylation of both eIF-4E and 4E-BP1.

31 eems to be the major regulator of the 4E-BP1-eIF-4E interaction in vivo.

32 using sequestering of eIF-4E, a TORC1/4E-BP1/eIF-4E-mediated mechanism of ERK activation could explai

33 le general protein synthesis is increased by eIF-4E overexpression in cultured cells, only a small pr

34 lated region (5'UTR) and may be regulated by eIF-4E, which melts mRNA secondary structure.

35 ell as relief of translational regulation by eIF-4E.

36 of proteins is preferentially upregulated by eIF-4E, as revealed by two-dimensional gel electrophores

37 in situ are not able to protect coexpressed eIF-4E BP1 from rapamycin-induced dephosphorylation.

38 For example, eIF-4E is usually increased in bronchioloalveolar carcin

39 reased the ability of both to bind exogenous eIF-4E.

40 ignancy will improve the capacity to exploit eIF-4E as a therapeutic target and as a marker for human

41 ylation of the translation initiation factor eIF-4E and inhibited host translation similarly under bo

42 and p85 S6 kinases and of initiation factor eIF-4E binding protein 1 (4E-BP1) 1-2 h after stimulatio

43 Initiation factor eIF-4E is a regulatory phosphoprotein whose phosphorylat

44 lations of the translation initiation factor eIF-4E on S209 and of its inhibitory binding protein 4E-

45 ciation of the translation initiation factor eIF-4E with its binding protein 4E-BP1, an inhibitor of

46 ch overexpress translation initiation factor eIF-4E, contain elevated levels of ornithine decarboxyla

47 ssential protein synthesis initiation factor eIF-4E.

48 ty to bind the translation initiation factor eIF-4E.

49 presses expression of the translation factor eIF-4E and the glutamate receptor subunit GluRIIA.

50 gulates expression of the translation factor eIF-4E at the NMJ, and Pum binds selectively to the 3'UT

51 red after purification of translation factor eIF-4E by 7-methyl guanosine triphosphate-Sepharose.

52 n antibody microarray was used to screen for eIF-4E-dependent proteins expressed during hypoxia.

53 on of 4E-BP1 and dissociation of 4E-BP1 from eIF-4E was blocked in cells treated with rapamycin, wort

54 o the functional dissociation of 4E-BP1 from eIF-4E.

55 r-69, leading to dissociation of 4E-BP1 from eIF-4E.

56 of 4BP-1, which causes it to dissociate from eIF-4E and allows eIF-4G to localize to the 5' cap.

57 is critical in causing its dissociation from eIF-4E, leaving 4E available to form translationally act

58 is results in its complete dissociation from eIF-4E.

59 hosphorylation of 4E-BP1 dissociates it from eIF-4E, relieving the translation block.

60 cell cycle progression in the face of global eIF-4E-mediated translation inhibition.

61 rest as a result of the inhibition of global eIF-4E-mediated translation.

62 and this inhibition is overcome by the high eIF-4E levels in 4E-P2 cells.

63 However, eIF-4E phosphorylation did not increase upon electrical

64 ith RNA-binding proteins, including ELAV/Hu, eIF-4E, and poly(A)-binding proteins.

65 em cells by using mRNA-binding proteins HuB, eIF-4E, and PABP that are known to play a role in transl

66 and promoted the dissociation of the PHAS-I*eIF-4E complex.

67 insufficient for dissociation of the PHAS-I.eIF-4E complex.

68 PHAS-I/eIF-4E association was measured as the amount of PHAS-I

69 induced by heat shock or Ad infection, (ii) eIF-4E is efficiently dephosphorylated during heat shock

70 These changes in eIF-4E phosphorylation account for differences in anabol

71 T3 cells, suggesting that high ODC levels in eIF-4E-overexpressing cells are the result of decreased

72 Reduction in eIF-4E expression by siRNA decreased tumor cell resistan

73 oM phorbol 12-myristate 13-acetate increased eIF-4E phosphorylation to 23 and 64%, respectively, but

74 action of adult feline cardiocytes increased eIF-4E phosphorylation to 34% after 4 h, as compared wit

75 nse RNA, or overexpression of the inhibitory eIF-4E binding proteins (4E-BPs), suppresses cellular tr

76 Translational initiation involving eIF-4E and its inhibitory binding protein 4E-BP1 appear

77 a 114-amino-acid region just proximal to its eIF-4E binding site.

78 nitiation factor 4E/MAPK-interacting kinase (eIF-4E/MNK) pathway.

79 Neither PML nor eIF-4E cause significant changes in cyclin D1 mRNA level

80 Our results implicate activation of eIF-4E as a key event in oncogenic transformation by pho

81 arlier data on transcriptional activation of eIF-4E expression by c-Myc suggest that eIF-4E is a down

82 Addition of eIF-4E overcomes PML induced retention and alters the mo

83 tional machinery by the tight association of eIF-4E binding proteins (4E-BPs).

84 th purvalanol A inhibited the association of eIF-4E with eIF-4G in PTX treated cells.

85 f 4E-BP1 by PTX increased the association of eIF-4E with eIF-4G, whereas cotreatment with purvalanol

86 ng both the activity and the availability of eIF-4E.

87 ates synaptic function via direct control of eIF-4E expression.

88 simultaneously inducing dephosphorylation of eIF-4E and BP-1, suggesting that cells might coordinatel

89 on of p70 S6 kinase and dephosphorylation of eIF-4E BP1, which become unresponsive to all agonists.

90 BP-1 without inhibiting dephosphorylation of eIF-4E induced by heat shock or Ad infection, (ii) eIF-4

91 tion is shown to induce dephosphorylation of eIF-4E.

92 Our data suggest that dissociation of eIF-4E from 4E-BP1, leading to an increase in the format

93 activation of MAP kinase and enhancement of eIF-4E and 4E-BP1 phosphorylation and dissociation and t

94 Furthermore, ectopic expression of eIF-4E blunted pp242-induced ERK phosphorylation.

95 ma of the lung, melanoma), the expression of eIF-4E is barely detectable.

96 protein synthesis, changes in the extent of eIF-4E phosphorylation were measured after imposition of

97 t that PTX-increases the functional level of eIF-4E by promoting the hyperphosphorylation and release

98 ves translational repression at the level of eIF-4E.

99 ibitor rapamycin and/or by overexpression of eIF-4E binding protein 1 (4E-BP1), which inhibits transl

100 Overexpression of eIF-4E in experimental models dramatically alters cellul

101 yclin production, but not phosphorylation of eIF-4E in BAEC.

102 alter the expression and phosphorylation of eIF-4E.

103 We suggest that independent regulation of eIF-4E and BP-1 might finely regulate the efficiency of

104 nclude that mTOR is an upstream regulator of eIF-4E BP1 as well as the p70 S6 kinase; moreover, these

105 duces phosphorylation of BP-1 and release of eIF-4E.

106 A deeper understanding of the role of eIF-4E in regulating the translation of the diverse gene

107 In this report we explore the roles of eIF-4E in human neoplastic disorders of the colon and in

108 nt than rapamycin in causing sequestering of eIF-4E, a TORC1/4E-BP1/eIF-4E-mediated mechanism of ERK

109 es not obligatorily involve sequestration of eIF-4E by BP-1.

110 nt translation by promoting sequestration of eIF-4E.

111 th eIF-4E in vivo regardless of the state of eIF-4E phosphorylation.

112 y regulated by the phosphorylation states of eIF-4E and the 4E-binding protein, BP-1.

113 4E-binding protein (4E-BP1), a suppressor of eIF-4E in the dephosphorylated state.

114 J, and Pum binds selectively to the 3'UTR of eIF-4E mRNA.

115 y confirmed using a high affinity variant of eIF-4E to capture 5'-methylguanosine-capped RNA followed

116 Acute volume overload had no effect on eIF-4E phosphorylation.

117 P2), derived from NIH-3T3 cells, overexpress eIF-4E and exhibit characteristics of transformation, po

118 We found that c-Myc overrides eIF-4E-induced cellular senescence, whereas eIF-4E antag

119 osphorylation, promoted dissociation of PHAS.eIF-4E complexes, and decreased the ability of both to b

120 cascades and is a candidate to phosphorylate eIF-4E in cells.

121 In vitro, MNK1 rapidly phosphorylates eIF-4E at the physiologically relevant site, Ser209.

122 w herein that such mTOR mutants also protect eIF-4E BP1 against rapamycin-induced dephosphorylation,

123 ts association with the cap-binding protein, eIF-4E, in vitro, and phosphorylation of Thr-45 seems to

124 ontribution of the mRNA cap-binding protein, eIF-4E, to malignant transformation and progression has

125 vailability of the mRNA cap binding protein, eIF-4E, which is sequestered away from the translational

126 The proteins eIF-4E BP1 and p70 S6 kinase each undergo an insulin/mit

127 ctivates a translation initiation regulator, eIF-4E-binding protein 1 (4EBP), asymmetrically and trig

128 promotes G1 phase progression by stimulating eIF-4E-dependent translation initiation.

129 y regulates cap-dependent protein synthesis, eIF-4E contributes to malignancy by selectively enabling

130 We find that eIF-4E is increased in colon adenomas and carcinomas, an

131 n of eIF-4E expression by c-Myc suggest that eIF-4E is a downstream target of the APC/beta-catenin/Tc

132 These data suggest that eIF-4E phosphorylation is a mechanism by which increased

133 se results are consistent with the view that eIF-4E plays a role in carcinogenesis by increasing gene

134 ncluding the p70 ribosomal S6 kinase and the eIF-4E binding protein, 4E-BP1.

135 phorylation, resulted in dissociation of the eIF-4E-eIF-4G complex.

136 ranslational initiation of this mRNA through eIF-4E- and 5' cap-independent internal ribosomal entry.

137 Thus, factors in addition to eIF-4E may be involved in the regulation of ODC.

138 orylation of 4BP-1 that allows it to bind to eIF-4E.

139 lated exclusively in Thr36 remained bound to eIF-4E, indicating that phosphorylation of Thr36 is insu

140 4BP-1 dephosphorylation is not equivalent to eIF-4E inactivation and does not explain the antiprolife

141 Binding of the Ala64 mutant of PHAS-I to eIF-4E was abolished by MAP kinase, indicating that phos

142 fications inhibited the binding of PHAS-I to eIF-4E.

143 l interfering double-stranded RNA (siRNA) to eIF-4E decreased anchorage-independent growth of maligna

144 w that the initiation factor of translation (eIF-4E), a downstream effector of mTOR, has oncogenic ef

145 odels of acute hemodynamic overload in vivo, eIF-4E phosphorylation increased to 23% in response to l

146 eIF-4E-induced cellular senescence, whereas eIF-4E antagonizes c-Myc-dependent apoptosis in vivo.

147 f PML bodies suggesting a mechanism by which eIF-4E can modulate PML function.

148 with BP-1, and (iii) BP-1 is associated with eIF-4E in vivo regardless of the state of eIF-4E phospho

149 creased the amount of PHAS-I associated with eIF-4E.

150 P1 led to a decrease in its association with eIF-4E and an increase in its association with the eIF-4

151 The association with eIF-4E led us to investigate if PML could alter mRNA dis

152 A MB 231, which reduced its association with eIF-4E, but did not alter the expression and phosphoryla

153 S-I phosphorylation and its association with eIF-4E.

154 a decrease in the association of 4E-BP1 with eIF-4E.