| Interacting proteins: O75807 and P05198 |
Pubmed |
SVM Score :0.0 |
| Interestingly , the expression of GADD 34 stimulated by HSV infection parallels the status of eIF 2alpha phosphorylation . ^^^ |
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| Interacting proteins: O75807 and P05198 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O75807 and P05198 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O75807 and P05198 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O75807 and P05198 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O75807 and P05198 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O75807 and P05198 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O75807 and P05198 |
Pubmed |
SVM Score :0.0 |
| This report shows that gamma134 . 5 and PP 1 form a complex in the infected cells , that fractions containing this complex specifically dephosphorylate eIF 2alpha , and that both gamma134 . 5 and GADD 34 proteins contain the amino acid sequence motif common to subunits of PP 1 that is required for binding to the PP 1 catalytic subunit . ^^^ These results suggest that the carboxyl terminal domain of gamma134 . 5 protein has the structural and functional attributes of a subunit of PP 1 specific for eIF 2alpha , that it has evolved to preclude shut off of protein synthesis , and that GADD 34 may have a similar function . . ^^^ |
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| Interacting proteins: O75807 and P05198 |
Pubmed |
SVM Score :0.0 |
| The herpes simplex virus type 1 gamma34 . 5 gene product and the cellular GADD 34 protein both contain similar domains that can regulate the activity of eukaryotic initiation factor 2 ( eIF 2 ) , a critical translation initiation factor . ^^^ Viral mutants that lack the GADD 34 related function grow poorly on a variety of malignant human cells , as activation of the cellular PKR kinase leads to the accumulation of inactive , phosphorylated eIF 2 at late times postinfection . ^^^ Thus , an RNA binding , ribosome associated protein ( Us 11 ) and a GADD 34 related protein ( gamma34 . 5 ) both function in a signal pathway that regulates translation by modulating eIF 2 phosphorylation . . ^^^ |
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| Interacting proteins: O75807 and P05198 |
Pubmed |
SVM Score :0.0 |
| Feedback inhibition of the unfolded protein response by GADD 34 mediated dephosphorylation of eIF2alpha . ^^^ Despite normal activity of the cognate stress inducible eIF2alpha kinases PERK ( also known as PEK ) and GCN 2 , phospho eIF2alpha levels were markedly diminished in GADD 34 overexpressing cells . ^^^ GADD 34 formed a complex with the catalytic subunit of protein phosphatase 1 ( PP1c ) that specifically promoted the dephosphorylation of eIF2alpha in vitro . ^^^ Mutations that interfered with the interaction with PP1c prevented the dephosphorylation of eIF2alpha and blocked attenuation of CHOP by GADD 34 . ^^^ These findings implicate GADD 34 mediated dephosphorylation of eIF2alpha in a negative feedback loop that inhibits stress induced gene expression , and that might promote recovery from translational inhibition in the unfolded protein response . . ^^^ |
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| Interacting proteins: O75807 and P05198 |
Pubmed |
SVM Score :0.0 |
| While GADD 34 inhibited PP 1 catalyzed dephosphorylation of phosphorylase a , the GADD 34 bound PP 1 was an active eIF 2alpha phosphatase . ^^^ In brain extracts from active ground squirrels , GADD 34 bound both 1 1 and PP 1 and eIF 2alpha was largely dephosphorylated . ^^^ |
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| Interacting proteins: O75807 and P05198 |
Pubmed |
SVM Score :0.0 |
| The growth arrest and DNA damage inducible protein , GADD 34 , associates with protein phosphatase 1 ( PP 1 ) and promotes in vitro dephosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 , ( eIF 2 alpha ) . ^^^ In this report , we show that the expression of human GADD 34 in cultured cells reversed eIF 2 alpha phosphorylation induced by thapsigargin and tunicamycin , agents that promote protein unfolding in the endoplasmic reticulum ( ER ) . ^^^ GADD 34 expression also reversed eIF 2 alpha phosphorylation induced by okadaic acid but not that induced by another phosphatase inhibitor , calyculin A ( CA ) , which is a result consistent with PP 1 being a component of the GADD 34 assembled eIF 2 alpha phosphatase . ^^^ N terminal deletions of GADD 34 established that while PP 1 binding was necessary , it was not sufficient to promote eIF 2 alpha dephosphorylation in cells . ^^^ These data provide new insights into the mode of action of GADD 34 in assembling an ER associated eIF 2 alpha phosphatase that regulates protein translation in mammalian cells . . ^^^ |
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| Interacting proteins: O75807 and P05198 |
Pubmed |
SVM Score :0.0 |
| GADD 34 is a stress inducible regulatory subunit of a holophosphatase complex that dephosphorylates eIF2alpha , and has been hypothesized to play a role in translational recovery . ^^^ Here , we report that GADD 34 expression correlated temporally with eIF2alpha dephosphorylation late in the stress response . ^^^ Inactivation of both alleles of GADD 34 prevented eIF2alpha dephosphorylation and blocked the recovery of protein synthesis , normally observed late in the stress response . ^^^ |
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| Interacting proteins: O75807 and P05198 |
Pubmed |
SVM Score :0.0 |
| GADD 34 binds to protein phosphatase PP 1 and can attenuate the translational elongation of key transcriptional factors through dephosphorylation of eukaryotic initiation factor 2alpha ( eIF2alpha ) . ^^^ |
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| Interacting proteins: O75807 and P05198 |
Pubmed |
SVM Score :0.0 |
| The phosphorylation of eukaryotic translation initiation factor 2 alpha ( eIF2alpha ) at Ser 51 induced by thapsigargin or DTT was prolonged in GADD 34 / MEF , although following treatment with tunicamycin , the eIF2alpha phosphorylation level did not change in either GADD34+ / + or GADD 34 / cells . ^^^ |
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| Interacting proteins: O75807 and P05198 |
Pubmed |
SVM Score :0.0 |
| GADD 34 was recently identified as the factor that activates the type 1 protein serine / threonine phosphatase ( PP 1 ) , which dephosphorylates eIF 2 alpha during cellular stresses . ^^^ Our study delineates a negative feedback regulatory loop in which the eIF 2 alpha controlled inhibition of protein translation leads to GADD 34 induction , which promotes translational recovery . ^^^ We show that activating transcription factor 4 ( ATF 4 ) , which is paradoxically translated during the eIF 2 alpha mediated translational block , is required for the transactivation of the GADD 34 promoter in response to ER stress and amino acid deprivation . ^^^ Examination of ATF 4 / MEFs revealed an absence of GADD 34 induction , prolonged eIF 2 alpha phosphorylation , delayed protein synthesis recovery , and diminished translational up regulation of BiP during ER stress . ^^^ These studies demonstrate the essential role of GADD 34 in the resumption of protein synthesis , define the pathway for its induction , and reveal that cytoprotective unfolded protein response targets like BiP are sensitive to the eIF 2 alpha mediated block in translation . . ^^^ |
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| Interacting proteins: O75807 and P05198 |
Pubmed |
SVM Score :0.0 |
| Stress induced activation of GADD 34 feeds back negatively on this pathway by promoting eIF2alpha dephosphorylation , however , GADD 34 mutant cells retain significant eIF2alpha directed phosphatase activity . ^^^ |
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| Interacting proteins: O75807 and P05198 |
Pubmed |
SVM Score :0.0 |
| ATF 3 contributes to induction of the CHOP transcriptional factor in response to amino acid starvation , and loss of ATF 3 function significantly lowers stress induced expression of GADD 34 , an eIF 2 protein phosphatase regulatory subunit implicated in feedback control of the eIF 2 kinase stress response . ^^^ Overexpression of ATF 3 in mouse embryo fibroblasts partially bypasses the requirement for PEK for induction of GADD 34 in response to ER stress , further supporting the idea that ATF 3 functions directly or indirectly as a transcriptional activator of genes targeted by the eIF 2 kinase stress pathway . ^^^ |
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| Interacting proteins: O75807 and P05198 |
Pubmed |
SVM Score :0.0 |
| The overexpression of a C terminal fragment of GADD 34 that constitutively dephosphorylates eIF2alpha was able to attenuate the phosphorylation of eIF2alpha and severely inhibit the induction of ATF 4 in response to hypoxic stress . ^^^ These studies demonstrate the essential role of ATF 4 in the response to hypoxic stress , define the pathway for its induction , and reveal that GADD 34 , a target of ATF 4 activation , negatively regulates the eIF2alpha mediated inhibition of translation . ^^^ |
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| Interacting proteins: O75807 and P05198 |
Pubmed |
SVM Score :0.0 |
| We find that CHOP directly activates GADD 34 , which promotes ER client protein biosynthesis by dephosphorylating phospho Ser 51 of the alpha subunit of translation initiation factor 2 ( eIF2alpha ) in stressed cells . ^^^ Furthermore , mice lacking GADD 34 directed eIF2alpha dephosphorylation , like CHOP ( / ) mice , are resistant to renal toxicity of the ER stress inducing drug tunicamycin . ^^^ |
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| Interacting proteins: O75807 and P05198 |
Pubmed |
SVM Score :0.0 |
| In contrast , PEG 3 was unable to block other GADD 34 induced changes , including eIF 2 alpha dephosphorylation , indicating that its effects on GADD 34 may be related more to its effect on cell growth rather than a global inhibitor of all GADD 34 functions . ^^^ |
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| Interacting proteins: O75807 and P05198 |
Pubmed |
SVM Score :0.0 |
| The C terminal region of GADD 34 has homology with the Herpes Simplex Virus protein , ICP34 . 5 , which overcomes the protein synthesis block after viral infection by actively dephosphorylating eukaryotic translation initiation factor 2alpha ( eIF2alpha ) . ^^^ The carboxy terminus of GADD 34 is also capable of dephosphorylating eIF2alpha and therefore has the capacity to restore the protein synthesis shutoff associated with ischaemia . ^^^ |
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| Interacting proteins: O75807 and P05198 |
Pubmed |
SVM Score :0.0 |
| Expression of the C terminal fragment of GADD 34 , which causes constitutive dephosphorylation of eIF2alpha , fully compensated for the stimulatory effect of alphaB crystallin on protein synthesis in heat shocked cells , but only partially for that of Hsp 27 . ^^^ |
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| Interacting proteins: O75807 and P05198 |
Pubmed |
SVM Score :0.0 |
| In addition , although ER stress potently induced the GADD 34 cellular eIF2alpha phosphatase subunit in uninfected cells , it did not accumulate to detectable levels in HSV 1 infected cells under identical exposure conditions . ^^^ |
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