| Interacting proteins: Q53EL6 and P60842 |
Pubmed |
SVM Score :0.0 |
| The tumor suppressor programmed cell death protein 4 ( PDCD 4 ) inhibits the translation initiation factor eIF4A , an RNA helicase that catalyzes the unwinding of secondary structure at the 5 ' untranslated region ( 5 ' UTR ) of messenger RNAs ( mRNAs ) . ^^^ |
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| Interacting proteins: Q53EL6 and P60842 |
Pubmed |
SVM Score :0.0 |
| Immunofluorescent confocal microscopy showed that Pdcd 4 colocalizes with eIF4A in the cytoplasm . eIF4A is an ATP dependent RNA helicase needed to unwind 5 ' mRNA secondary structure . ^^^ Recombinant Pdcd 4 specifically inhibited the helicase activity of eIF4A and eIF4F . ^^^ In contrast , Pdcd 4 ( D418A ) , a mutant inactivated for binding to eIF4A , failed to inhibit cap dependent or IRES dependent translation or AP 1 transactivation . ^^^ Recombinant Pdcd 4 prevented eIF4A from binding to the C terminal region of eIF4G ( amino acids 1040 to 1560 ) but not to the middle region of eIF4G ( amino acids 635 to 1039 ) . ^^^ The mechanism by which Pdcd 4 inhibits translation thus appears to involve inhibition of eIF4A helicase , interference with eIF4A association dissociation from eIF4G , and inhibition of eIF4A binding to the C terminal domain of eIF4G . ^^^ |
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| Interacting proteins: Q53EL6 and P60842 |
Pubmed |
SVM Score :0.0 |
| Programmed cell death 4 ( Pdcd 4 ) , originally identified as an inhibitor of murine cellular transformation , inhibits protein synthesis by directly interacting with eukaryotic initiation factor 4A ( eIF4A ) of the translation initiation complex . ^^^ |
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| Interacting proteins: Q53EL6 and P60842 |
Pubmed |
SVM Score :0.83782196 |
| Pdcd 4 directly interacts with the RNA helicase eIF4A and inhibits protein synthesis by interfering with the assembly of the cap dependent translation initiation complex . 0.83782196^^^ |
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| Interacting proteins: Q53EL6 and P60842 |
Pubmed |
SVM Score :0.7696671 |
| A competition experiment revealed that Pdcd 4 competes with C terminal eIF4G for binding to eIF4A . 0.7696671^^^ |
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| Interacting proteins: Q53EL6 and P60842 |
Pubmed |
SVM Score :0.0 |
| Mutation of amino acid residues conserved between Pdcd 4 and eIF4Gc but not in DAP 5 / NAT1 / p97 to the amino acid residues found in the DAP 5 / NAT1 / p97 indicates that some of these amino acid residues within the MA 3 domain are critical for eIF4A binding activity . ^^^ Six Pdcd 4 mutants ( Pdcd 4 ( E249K ) , Pdcd 4 ( D253A ) , Pdcd 4 ( D414K ) , Pdcd 4 ( D418A ) , Pdcd 4 ( E249K , D414K ) , and Pdcd 4 ( D253A , D418A ) ) lost > 90 % eIF4A binding activity . ^^^ These results demonstrate that the MA 3 domain is important for eIF4A binding and explain the ability of Pdcd 4 or eIF4Gc but not DAP 5 / NAT1 / p97 to bind to eIF4A . ^^^ Competition experiments indicate that Pdcd 4 prevents ca . 60 to 70 % of eIF4A binding to eIF4Gc at a Pdcd4 / eIF4A ratio of 1 : 1 , but mutants Pdcd 4 ( D253A ) and Pdcd 4 ( D253A , D418A ) do not . ^^^ Together , these results indicate that not only binding to eIF4A but also prevention of eIF4A binding to the MA 3 domain of eIF4Gc contributes to the mechanism by which Pdcd 4 inhibits translation . . ^^^ |
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| Interacting proteins: Q53EL6 and P60842 |
Pubmed |
SVM Score :0.0 |
| NA |
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