| Interacting proteins: Q99683 and Q12933 |
Pubmed |
SVM Score :0.79018622 |
| In untransfected mammalian cells , ASK 1 rapidly associates with TRAF 2 in a TNF dependent manner . 0.79018622^^^ |
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| Interacting proteins: Q99683 and Q12933 |
Pubmed |
SVM Score :0.0 |
| We report that TRAF 2 , TRAF 5 and TRAF 6 associate with apoptosis signal regulating kinase 1 ( ASK 1 ) , and a catalytically inactive ASK 1 mutant blocks stress activated protein kinase ( SAPK ) / Jun NH 2 terminal kinase ( JNK ) activation by these TRAFs . ^^^ A truncated derivative of TRAF 2 , which inhibits SAPK activation by TNF , blocks TNF induced ASK 1 activation . ^^^ Furthermore , protection from TNF induced cell death conferred by an ASK 1 mutant is dependent upon TRAF 2 . ^^^ Hence , ASK 1 is a common mediator of TRAF regulated SAPK and apoptosis signaling , and the TRAF 2 ASK 1 connection completes the signaling cascade from TNF to SAPK / JNK activation . . ^^^ |
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| Interacting proteins: Q99683 and Q12933 |
Pubmed |
SVM Score :0.0 |
| Here we show that TNF receptor ( TNFR ) associated factor 2 ( TRAF 2 ) , an adapter protein that couples TNFRs to the SAPKs and p38s , can activate ASK 1 in vivo and can interact in vivo with the amino and carboxyl terminal noncatalytic domains of the ASK 1 polypeptide . ^^^ Expression of the amino terminal noncatalytic domain of ASK 1 can inhibit TNF and TRAF 2 activation of SAPK . ^^^ We demonstrate that Trx significantly inhibits TRAF 2 activation of SAPK and blocks the ASK 1 TRAF2 interaction in a reaction reversed by oxidants . ^^^ We show that expression of ASK 1 with TRAF 2 enhances in vivo ASK 1 homo oligomerization in a manner dependent , in part , upon the TRAF 2 RING effector domain and the generation of ROS . ^^^ Thus , activation of ASK 1 by TNF requires the ROS mediated dissociation of Trx possibly followed by the binding of TRAF 2 and consequent ASK 1 homo oligomerization . . ^^^ |
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| Interacting proteins: Q99683 and Q12933 |
Pubmed |
SVM Score :0.0 |
| Trx induced ASK 1 ubiquitination / degradation could be blocked by ASK 1 activators TNF and TRAF 2 . ^^^ |
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| Interacting proteins: Q99683 and Q12933 |
Pubmed |
SVM Score :0.0 |
| Tumor necrosis factor ( TNF ) induced activation of apoptosis signal regulating kinase 1 ( ASK 1 ) and germinal center kinases ( GCKs ) and the subsequent activation of stress activated protein kinases ( SAPKs and c Jun NH ( 2 ) terminal kinases ) requires TNF receptor associated factor 2 ( TRAF 2 ) . ^^^ Although the TRAF 2 TRAF domain binds ASK 1 , GCK , and the highly related kinase GCKR , the RING finger domain is needed for their activation . ^^^ Interference with Ubc 13 function or expression inhibits both TNF and TRAF 2 mediated GCKR and SAPK activation , but has a minimal effect on ASK 1 activation . ^^^ These results indicate that the assembly of a TRAF 2 lysine 63 linked polyubiquitin chain by Ubc13 / Uev1A is required for TNF mediated GCKR and SAPK activation , but may not be required for ASK 1 activation . . ^^^ |
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| Interacting proteins: Q99683 and Q12933 |
Pubmed |
SVM Score :0.0 |
| Similar to JNK 1 activation , we also observed that low glucose induced ASK 1 activation , dissociation of GRX and thioredoxin ( TRX ) from ASK 1 , dimerization of ASK 1 , and association of Daxx and TRAF 2 with ASK 1 significantly occurred at a glucose concentration less than or equal to 0 . 01 mM . . ^^^ |
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| Interacting proteins: Q99683 and Q12933 |
Pubmed |
SVM Score :0.0 |
| ASK 1 induced apoptotic activity is up regulated by two cellular factors , Daxx and TRAF 2 , through direct protein protein interactions . ^^^ |
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| Interacting proteins: Q99683 and Q12933 |
Pubmed |
SVM Score :0.0 |
| AIP1 / DAB2IP , a novel member of the Ras GAP family , transduces TRAF 2 induced ASK 1 JNK activation . ^^^ An AIP 1 mutant with deletion of this proline rich region constitutively binds to TRAF 2 and ASK 1 . ^^^ A PERIOD like domain ( amino acids 591 719 ) of AIP 1 binds to the intact RING finger of TRAF 2 , and specifically enhances TRAF 2 induced ASK 1 activation . ^^^ Taken together , our data suggest that AIP 1 is a novel transducer in TNF induced TRAF 2 dependent activation of ASK 1 that mediates a balance between JNK versus NF kappaB signaling . . ^^^ |
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| Interacting proteins: Q99683 and Q12933 |
Pubmed |
SVM Score :0.0 |
| Upon H ( 2 ) O ( 2 ) treatment , the ASK 1 signalosome forms a higher molecular mass complex at least in part because of the recruitment of tumor necrosis factor receptor associated factor 2 ( TRAF 2 ) and TRAF 6 . ^^^ Consistent with our previous findings that TRAF 2 and TRAF 6 activate ASK 1 , H ( 2 ) O ( 2 ) induced ASK 1 activation and cell death were strongly reduced in the cells derived from Traf 2 / and Traf 6 / mice . ^^^ A novel signaling complex including TRAF 2 , TRAF 6 , and ASK 1 may thus be the key component in oxidative stress induced cell death . . ^^^ |
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| Interacting proteins: Q99683 and Q12933 |
Pubmed |
SVM Score :0.0 |
| Glutathione S transferase P 1 1 also attenuated TRAF 2 enhanced apoptosis signal regulating kinase 1 ( ASK 1 ) autophosphorylation and inhibited TRAF 2 ASK1 induced cell apoptosis by suppressing the interaction of TRAF 2 and ASK 1 . ^^^ Conversely , silencing of GSTP 1 1 expression through RNA interference ( RNAi ) resulted in increase of TNF alpha dependent TRAF 2 ASK1 association followed by hyper activation of ASK 1 and JNK . ^^^ |
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| Interacting proteins: Q99683 and Q12933 |
Pubmed |
SVM Score :0.0 |
| PURPOSE : Tumor necrosis factor alpha ( TNF alpha ) exerts apoptosis throughout an intracellular transduction pathway that involves the protein kinases TRAF 2 ( integration point of apoptotic and survival signals ) , signal regulating kinase ( ASK 1 ) ( pro apoptotic protein ) , mitogen activated protein kinase kinase 4 ( MEK 4 ) ( p 38 activator and metastasis suppressor gene ) , Jun N terminal kinase ( JNK ) ( stress mitogen activated protein kinase ) and the transcription factor activator protein 1 ( AP 1 ) . ^^^ RESULTS : In normal prostates immunoreactions to TRAF 2 , ASK 1 , MEK 4 and JNK were positive , while no immunoreaction to AP 1 was detected . ^^^ Although in benign prostatic hyperplasia the percent of immunostained specimens and intensity of immunoreactions to TRAF 2 , ASK 1 , MEK 4 and JNK decreased , the immunoreaction to AP 1 was positive in 27 . 3 % . ^^^ |
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| Interacting proteins: Q99683 and Q12933 |
Pubmed |
SVM Score :0.0 |
| Ebselen inhibited TNF alpha induced TNF receptor associated factor 2 ( TRAF 2 ) ASK 1 complex formation and phosphorylation of stress activated protein kinase ERK kinase 1 ( SEK 1 ) , which is an upstream signaling molecule of JNK . ^^^ |
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| Interacting proteins: Q99683 and Q12933 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q99683 and Q12933 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q99683 and Q12933 |
Pubmed |
SVM Score :0.0 |
| NA |
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