ライフサイエンスコーパス: eIF-2alpha

1 unit of translation initiation factor eIF-2 (eIF-2alpha).

2 a subunit of eukaryotic initiation factor 2 (eIF-2alpha) and inhibit translation, we determined wheth

3 eukaryotic translation initiation factor 2 (eIF-2alpha) and the induction of apoptosis in lung cance

4 eukaryotic translation initiation factor 2 (eIF-2alpha) and to apoptotic cell death.

5 a subunit of eukaryotic initiation factor 2 (eIF-2alpha) by activated PKR, and, if provided prior to

6 a subunit of eukaryotic initiation factor 2 (eIF-2alpha) is a well-characterized mechanism regulating

7 a subunit of eukaryotic initiation factor 2 (eIF-2alpha) phosphorylation and initial suppression of v

8 a subunit of eukaryotic initiation factor 2 (eIF-2alpha) phosphorylation.

9 it of protein synthesis initiation factor 2 (eIF-2alpha) was elevated severalfold in DeltaE3L-infecte

10 eukaryotic translation initiation factor 2 (eIF-2alpha) was enhanced approximately 3-fold in polR ve

11 eukaryotic translation initiation factor 2 (eIF-2alpha), a process that prevents polypeptide chain i

12 a subunit of eukaryotic initiation factor 2 (eIF-2alpha), as well as induce robust accumulation of ac

13 a subunit of eukaryotic initiation factor 2 (eIF-2alpha), was equally phosphorylated in EBV-positive

14 eukaryotic translation initiation factor 2 (eIF-2alpha).

15 eukaryotic translation initiation factor 2 (eIF-2alpha).

16 eukaryotic translation initiation factor 2 (eIF-2alpha).

17 in synthesis eukaryotic initiation factor 2 (eIF-2alpha).

18 a subunit of eukaryotic initiation factor-2 (eIF-2alpha) and inhibition of protein synthesis.

19 a subunit of eukaryotic initiation factor-2 (eIF-2alpha).

20 ity and eukaryotic initiation factor 2alpha (eIF-2alpha) dephosphorylation, a finding consistent with

21 gulated eukaryotic initiation factor 2alpha (eIF-2alpha) kinase (HRI) interacts with hsp90 in situ in

22 ryotic translation initiation factor 2alpha (eIF-2alpha).

23 tion of eukaryotic initiation factor 2alpha (eIF-2alpha).

24 ryotic translation initiation factor-2alpha (eIF-2alpha) is one of the key steps where protein synthe

25 unit of eukaryotic initiation factor-2alpha (eIF-2alpha) kinase (HRI).

26 esis by eukaryotic initiation factor-2alpha (eIF-2alpha) phosphorylation is a highly conserved phenom

27 creased eukaryotic initiation factor-2alpha (eIF-2alpha) phosphorylation.

28 KR) and eukaryotic initiation factor-2alpha (eIF-2alpha) was determined by Western blot.

29 eletions of amino acids 238 to 258 abolished eIF-2alpha phosphatase activity but not PP1 binding acti

30 tranded protein kinase R (PKR) is activated, eIF-2alpha is phosphorylated, and protein synthesis is s

31 rylase a, the GADD34-bound PP1 was an active eIF-2alpha phosphatase.

32 lates translation initiation factor 2-alpha (eIF-2alpha), and inhibits translation.

33 ence and structural features conserved among eIF-2alpha kinases, PEK contains a distinctive amino-ter

34 nsistent with GADD34's role in assembling an eIF-2alpha phosphatase.

35 of protein synthesis and the presence of an eIF-2alpha kinase has not been demonstrated in higher pl

36 These results suggest that an eIF-2alpha-dependent translation inhibition mechanism is

37 In yeast, an eIF-2alpha kinase, GCN2, functions in translational cont

38 lation initiation factors, p220 (eIF-4G) and eIF-2alpha, are cleaved as a result of hemin treatment o

39 pha, that correlated with PKR activation and eIF-2alpha phosphorylation.

40 lted in restoration of both PKR activity and eIF-2alpha phosphorylation, concomitant with growth supp

41 This HRI was an active autokinase and eIF-2alpha kinase, and its kinase activities were inhibi

42 tation resisted translational inhibition and eIF-2alpha phosphorylation in response to ER or cytoplas

43 IF-4E, p26), eIF-iso4F (eIF-iso4E, p28), and eIF-2alpha (p42) were altered during germination, sugges

44 reater degrees of phosphorylation of PKR and eIF-2alpha than did control extracts.

45 In correlation, phosphorylation of PKR and eIF-2alpha was suppressed in cells expressing the VP35 p

46 Increased phosphorylation of PKR and eIF-2alpha were also observed in active IBD tissues.

47 squirrels, GADD34 bound both I-1 and PP1 and eIF-2alpha was largely dephosphorylated.

48 In these cells, PKR is activated but eIF-2alpha is not phosphorylated, and the phosphatase is

49 osphorylation was shown to be carried out by eIF-2alpha kinases PKR and HRI.

50 nslational level by decreasing PKR-dependent eIF-2alpha phosphorylation.

51 ding mammalian double-stranded RNA-dependent eIF-2alpha kinase (PKR) and heme-regulated inhibitor kin

52 ng this complex specifically dephosphorylate eIF-2alpha, and that both gamma134.5 and GADD34 proteins

53 s ability to redirect PP1 to dephosphorylate eIF-2alpha and replication of mutant viruses was severel

54 and redirects phosphatase to dephosphorylate eIF-2alpha to enable continued protein synthesis despite

55 e 1alpha and redirects it to dephosphorylate eIF-2alpha, thus enabling sustained protein synthesis.

56 phatase is not redirected to dephosphorylate eIF-2alpha.

57 o form a large complex that dephosphorylates eIF-2alpha and thereby prevents translation shutoff medi

58 lecular-weight complex that dephosphorylates eIF-2alpha.

59 ion is carried out in part by three distinct eIF-2alpha kinases including mammalian double-stranded R

60 In isolation, pUL38 overexpression elevated eIF-2alpha phosphorylation, induced ATF4 accumulation, l

61 phorylation of translation initiation factor eIF-2alpha seen following plasmid DNA transfection were

62 the eukaryotic translation initiation factor eIF-2alpha, the activation of RNase L, and the shutoff o

63 ylation of the translation initiation factor eIF-2alpha.

64 ylation of the translation initiation factor eIF-2alpha.

65 ation of protein synthesis initiation factor eIF-2alpha.

66 of eukaryotic translation initiation factor (eIF-2alpha).

67 ng phosphorylation of the initiation factor, eIF-2alpha.

68 lacked the phosphatase activity specific for eIF-2alpha characteristic of wild-type virus-infected ce

69 attributes of a subunit of PP1 specific for eIF-2alpha, that it has evolved to preclude shut-off of

70 the inhibition of translation resulting from eIF-2alpha phosphorylation.

71 and cDNA clones homologous to the yeast GCN2 eIF-2alpha kinase (yGCN2) were isolated from Drosophila

72 the absence of the viral gamma(1)34.5 gene, eIF-2alpha is phosphorylated and protein synthesis is pr

73 cinoma cells with Myb34.5 results in greater eIF-2alpha dephosphorylation and viral replication compa

74 was attributed to an NS5A-mediated block in eIF-2alpha phosphorylation.

75 t-infection, concomitant with an increase in eIF-2alpha phosphorylation and an increase in NF-kappaB

76 uiring the serine-51 phosphorylation site in eIF-2alpha.

77 the known regulatory phosphorylation site in eIF-2alpha.

78 the unfolded protein response (UPR)-induced eIF-2alpha phosphorylation to protect against endoplasmi

79 lates protein homeostasis through inhibiting eIF-2alpha kinases including double-stranded RNA-depende

80 eement with the hypothesis that K3L inhibits eIF-2alpha kinases by functioning as a pseudosubstrate,

81 includes BiP and XBP-1, and another that is eIF-2alpha kinase-dependent, which includes ATF4 and GAD

82 plant eIF-2alpha (peIF-2alpha) and mammalian eIF-2alpha (meIF-2alpha) are phosphorylated similarly by

83 gether, our studies identify a new mammalian eIF-2alpha kinase, GCN2, that can mediate translational

84 PKR in yeast, P58IPK repressed PKR-mediated eIF-2alpha phosphorylation, inhibiting the normally toxi

85 PKR function and inhibition of PKR-mediated eIF-2alpha phosphorylation.

86 gamma(1)34.5 protein is capable of mediating eIF-2alpha dephosphorylation without any other viral pro

87 -) virus carrying the compensatory mutation, eIF-2alpha is not phosphorylated.

88 sembly of SGs, whereas a nonphosphorylatable eIF-2alpha mutant (S51A) prevents the assembly of SGs.

89 gulatory phosphorylation site (serine 51) of eIF-2alpha.

90 Specific dephosphorylation of eIF-2alpha was not demonstrable.

91 oduct that promotes the dephosphorylation of eIF-2alpha) that is under control of the E2F-responsive

92 thesis by causing rapid dephosphorylation of eIF-2alpha, in cells infected with gamma134.5(-) virus c

93 ex that is required for dephosphorylation of eIF-2alpha.

94 eplacement of the truncated viral homolog of eIF-2alpha (FV3-DeltavIF-2alpha) or the 18K IE gene (FV3

95 lysis indicates that hyperphosphorylation of eIF-2alpha caused by HSV is greater in PKR+/+ cells than

96 to inhibit growth by hyperphosphorylation of eIF-2alpha, requiring both the kinase catalytic domain a

97 wth phenotype due to hyperphosphorylation of eIF-2alpha.

98 lting in phosphorylation and inactivation of eIF-2alpha, an essential factor in protein translation.

99 in mouse 3T6 cells, which is independent of eIF-2alpha dephosphorylation.

100 Induction of eIF-2alpha phosphorylation by Gcn2p during glucose limit

101 on of C114 protein inhibits the induction of eIF-2alpha phosphorylation following poly(I.C) treatment

102 indicate that K3L is a specific inhibitor of eIF-2alpha kinases from mammals and yeast and suggest th

103 of K3L protein in yeast reduced the level of eIF-2alpha phosphorylation by GCN2 and blocked the stimu

104 ocytes with Myb34.5 results in low levels of eIF-2alpha dephosphorylation and viral replication that

105 Mutation of eIF-2alpha to prevent phosphorylation also impaired IFN-

106 for glucose induces Gcn2p phosphorylation of eIF-2alpha and stimulates GCN4 translation.

107 The mutant blocks the phosphorylation of eIF-2alpha but does not restore the virulence phenotype

108 n for amino acids induces phosphorylation of eIF-2alpha by Gcn2 protein kinase, leading to elevated t

109 assays, US11 blocked the phosphorylation of eIF-2alpha by PKR activated by poly(I-C); and (iv) US11

110 synthesis associated with phosphorylation of eIF-2alpha by the activated PKR is not readily explainab

111 RF63 mutant had increased phosphorylation of eIF-2alpha compared with cells infected with parental vi

112 ces are required for GCN2 phosphorylation of eIF-2alpha in an in vitro assay.

113 nduced PKR activation and phosphorylation of eIF-2alpha in IFN-treated cells, resulting in high level

114 ino acids also stimulates phosphorylation of eIF-2alpha in mammalian cells, we searched for and ident

115 rylation and PKR-mediated phosphorylation of eIF-2alpha in vitro.

116 -2alpha kinases including phosphorylation of eIF-2alpha in vitro.

117 have been shown to block phosphorylation of eIF-2alpha in vivo and the subsequent stimulation of the

118 Phosphorylation of eIF-2alpha induces the translational expression of GCN4,

119 Phosphorylation of eIF-2alpha results in attenuation of protein translation

120 in acts downstream of the phosphorylation of eIF-2alpha to promote the sequestration of untranslated

121 of protein synthesis, the phosphorylation of eIF-2alpha, and activation of RNase L.

122 somes may enhance in vivo phosphorylation of eIF-2alpha, by providing PKR access to its substrate.

123 to PKR and precludes the phosphorylation of eIF-2alpha, whereas US11 driven by its natural promoter

124 ) SGs is initiated by the phosphorylation of eIF-2alpha.

125 not required for in vitro phosphorylation of eIF-2alpha.

126 ng chemicals caused rapid phosphorylation of eIF-2alpha.

127 esis may be regulated via phosphorylation of eIF-2alpha.

128 viral proteins inhibited phosphorylation of eIF-2alpha.

129 Protection of eIF-2alpha phosphorylation with systemically administere

130 hese observations suggest that regulation of eIF-2alpha phosphorylation by the gamma(1)34.5 protein i

131 ted by HSV infection parallels the status of eIF-2alpha phosphorylation.

132 virus is homologous to the amino terminus of eIF-2alpha and is thought to inhibit the activity of the

133 om the gamma(1)34.5 protein has no effect on eIF-2alpha dephosphorylation, further truncations up to

134 virus did not significantly increase PKR or eIF-2alpha phosphorylation in either PKR-sufficient or -

135 PEK, which shares common features with other eIF-2alpha kinases including phosphorylation of eIF-2alp

136 new related kinase, which we term pancreatic eIF-2alpha kinase, or PEK.

137 e(s) shared by other cellular stresses (PERK/eIF-2alpha phosphorylation-dependent).

138 A phosphomimetic eIF-2alpha mutant (S51D) induces the assembly of SGs, wh

139 with HSV-1(F) or R5104 did not phosphorylate eIF-2alpha.

140 binant enzyme can specifically phosphorylate eIF-2alpha on serine-51.

141 rwent autophosphorylation and phosphorylated eIF-2alpha with a specific activity of approximately 50%

142 , contained an activity which phosphorylated eIF-2alpha in vitro, whereas lysates of mock-infected ce

143 While phosphorylated eIF-2alpha was undetectable in uninfected cells or cells

144 ng cell defense responses by phosphorylating eIF-2alpha, thus suppressing RNA translation.

145 tion of protein synthesis by phosphorylating eIF-2alpha.

146 Protein kinases capable of phosphorylating eIF-2alpha have been characterized from mammals and yeas

147 GCN2 autophosphorylation and phosphorylation eIF-2alpha.

148 nistically, we found that IL-32 used the PKR-eIF-2alpha as well as the MxA antiviral pathways.

149 We show that plant eIF-2alpha (peIF-2alpha) and mammalian eIF-2alpha (meIF-

150 GCN2 were found to phosphorylate recombinant eIF-2alpha substrate.

151 Phosphorylation of the recombinant eIF-2alpha substrate was dependent on both GCN2 kinase a

152 eneral control pathway, also greatly reduced eIF-2alpha phosphorylation in the in vitro assay.

153 of L18 by transient DNA transfection reduced eIF-2alpha phosphorylation and stimulated translation of

154 polypeptides into an active heme-regulatable eIF-2alpha kinase that exhibited slower electrophoretic

155 egulating the activity of the heme-regulated eIF-2alpha kinase (HRI) in hemin-supplemented rabbit ret

156 The heme-regulated eIF-2alpha kinase (HRI) is activated not only in heme-de

157 elates with the activation of heme-regulated eIF-2alpha kinase (HRI), which blocks the initiation of

158 n directly on the homogeneous heme-regulated eIF-2alpha kinase (HRI), which is activated during heme

159 ds to better activation of PKR and resultant eIF-2alpha phosphorylation.

160 culovirus, was capable of directing specific eIF-2alpha dephosphorylation.

161 UPR, including PERK, the ER stress-specific eIF-2alpha kinase; ATF4, an ER stress-induced transcript

162 important for recognition of their substrate eIF-2alpha.

163 eukaryotic initiation factor 2alpha subunit (eIF-2alpha) through a direct interaction, thereby reliev

164 Hsc70 suppressed eIF-2alpha phosphorylation and maintained the guanine nu

165 fically phosphorylating Ser51 in a synthetic eIF-2alpha peptide, a key characteristic of the eIF-2alp

166 Given that eIF-2alpha phosphorylation in mammals is induced in resp

167 These results indicate that eIF-2alpha dephosphorylation mediated by the gamma(1)34.

168 The eIF-2alpha-P phosphatase activities are sensitive to inh

169 614 with an alanine completely abolished the eIF-2alpha kinase activity, whereas the mutant PEK was s

170 ilities, whereas the other arm activates the eIF-2alpha (alpha subunit of eukaryotic initiation facto

171 pendent on both GCN2 kinase activity and the eIF-2alpha phosphorylation site, serine 51.

172 One SNP in the regulatory region of the eIF-2alpha gene revealed A/G alleles.

173 ort the concept that pPKR is a member of the eIF-2alpha kinase family.

174 -2alpha peptide, a key characteristic of the eIF-2alpha kinase family.

175 WT SV5 was a poor activator of the eIF-2alpha kinase protein kinase R (PKR).

176 identified that regulate the activity of the eIF-2alpha kinases.

177 mes that of mock-infected cells, whereas the eIF-2alpha-P phosphatase activity of gamma(1)34.5- virus

178 fer fish Fugu rubripes, suggesting that this eIF-2alpha kinase plays an important role in translation

179 In contrast to eIF-2alpha-P phosphatase activity, extracts of mock-infe

180 , and resistance to interferon is coupled to eIF-2alpha dephosphorylation.

181 contains a substrate domain with homology to eIF-2alpha in close proximity to an essential binding do

182 the unfolded protein response (UPR), lead to eIF-2alpha phosphorylation and increased expression of C

183 orylates both mutant K296P PKR and wild-type eIF-2alpha in vitro.

184 in brain from hibernating animals, in which eIF-2alpha was highly phosphorylated at serine-51 and pr

185 hough both NAFL and NASH are associated with eIF-2alpha phosphorylation, there is a failure to activa

186 ionally substituted for the endogenous yeast eIF-2alpha kinase, GCN2, by a process requiring the seri

187 essed and purified a truncated form of yeast eIF-2alpha.

188 er K3L can inhibit the activity of the yeast eIF-2alpha kinase GCN2.