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Interleukin-1 and TRAF6-dependent activation of TAK1 in the absence of TAB2 and TAB3
Interleukin-1 (IL-1) signaling induces the formation of Lys63-linked ubiquitin (K63-Ub) chains, which are thought to activate the ‘master’ protein kinase TGFβ-activated kinase 1 (TAK1) by interacting with its TAK1-binding 2 (TAB2) and TAB3 subunits. Here, we report that IL-1β can also activate the T...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5632801/ https://www.ncbi.nlm.nih.gov/pubmed/28507161 http://dx.doi.org/10.1042/BCJ20170288 |
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author | Zhang, Jiazhen Macartney, Thomas Peggie, Mark Cohen, Philip |
author_facet | Zhang, Jiazhen Macartney, Thomas Peggie, Mark Cohen, Philip |
author_sort | Zhang, Jiazhen |
collection | PubMed |
description | Interleukin-1 (IL-1) signaling induces the formation of Lys63-linked ubiquitin (K63-Ub) chains, which are thought to activate the ‘master’ protein kinase TGFβ-activated kinase 1 (TAK1) by interacting with its TAK1-binding 2 (TAB2) and TAB3 subunits. Here, we report that IL-1β can also activate the TAB1–TAK1 heterodimer present in TAB2/TAB3 double knockout (DKO) IL-1 receptor-expressing cells. The IL-1β-dependent activation of the TAB1–TAK1 heterodimer in TAB2/3 DKO cells is required for the expression and E3 ligase activity of tumor necrosis factor receptor-associated factor 6 (TRAF6) and is reduced by the small interfering RNA (siRNA) knockdown of ubiquitin conjugating 13 (Ubc13), an E2-conjugating enzyme that directs the formation of K63-Ub chains. IL-1β signaling was restored to TAB1/2/3 triple KO cells by the re-expression of either TAB1 or TAB2, but not by an ubiquitin binding-defective mutant of TAB2. We conclude that IL-1β can induce the activation of TAK1 in two ways, only one of which requires the binding of K63-Ub chains to TAB2/3. The early IL-1β-stimulated, TAK1-dependent activation of p38α mitogen-activated protein (MAP) kinase and the canonical IκB kinase (IKK) complex, as well as the NF-κB-dependent transcription of immediate early genes, was similar in TAB2/3 DKO cells and TAB2/3-expressing cells. However, in contrast with TAB2/3-expressing cells, IL-1β signaling was transient in TAB2/3 DKO cells, and the activation of c-Jun N-terminal kinase 1 (JNK1), JNK2 and p38γ was greatly reduced at all times. These observations indicate a role for TAB2/3 in directing the TAK1-dependent activation of MAP kinase kinases that switch on JNK1/2 and p38γ MAP kinases. These observations and the transient activation of the TAB1–TAK1 heterodimer may explain why IL-1β-dependent IL-8 mRNA formation was abolished in TAB2/3 DKO cells. |
format | Online Article Text |
id | pubmed-5632801 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-56328012017-10-23 Interleukin-1 and TRAF6-dependent activation of TAK1 in the absence of TAB2 and TAB3 Zhang, Jiazhen Macartney, Thomas Peggie, Mark Cohen, Philip Biochem J Research Articles Interleukin-1 (IL-1) signaling induces the formation of Lys63-linked ubiquitin (K63-Ub) chains, which are thought to activate the ‘master’ protein kinase TGFβ-activated kinase 1 (TAK1) by interacting with its TAK1-binding 2 (TAB2) and TAB3 subunits. Here, we report that IL-1β can also activate the TAB1–TAK1 heterodimer present in TAB2/TAB3 double knockout (DKO) IL-1 receptor-expressing cells. The IL-1β-dependent activation of the TAB1–TAK1 heterodimer in TAB2/3 DKO cells is required for the expression and E3 ligase activity of tumor necrosis factor receptor-associated factor 6 (TRAF6) and is reduced by the small interfering RNA (siRNA) knockdown of ubiquitin conjugating 13 (Ubc13), an E2-conjugating enzyme that directs the formation of K63-Ub chains. IL-1β signaling was restored to TAB1/2/3 triple KO cells by the re-expression of either TAB1 or TAB2, but not by an ubiquitin binding-defective mutant of TAB2. We conclude that IL-1β can induce the activation of TAK1 in two ways, only one of which requires the binding of K63-Ub chains to TAB2/3. The early IL-1β-stimulated, TAK1-dependent activation of p38α mitogen-activated protein (MAP) kinase and the canonical IκB kinase (IKK) complex, as well as the NF-κB-dependent transcription of immediate early genes, was similar in TAB2/3 DKO cells and TAB2/3-expressing cells. However, in contrast with TAB2/3-expressing cells, IL-1β signaling was transient in TAB2/3 DKO cells, and the activation of c-Jun N-terminal kinase 1 (JNK1), JNK2 and p38γ was greatly reduced at all times. These observations indicate a role for TAB2/3 in directing the TAK1-dependent activation of MAP kinase kinases that switch on JNK1/2 and p38γ MAP kinases. These observations and the transient activation of the TAB1–TAK1 heterodimer may explain why IL-1β-dependent IL-8 mRNA formation was abolished in TAB2/3 DKO cells. Portland Press Ltd. 2017-07-01 2017-06-26 /pmc/articles/PMC5632801/ /pubmed/28507161 http://dx.doi.org/10.1042/BCJ20170288 Text en © 2017 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Articles Zhang, Jiazhen Macartney, Thomas Peggie, Mark Cohen, Philip Interleukin-1 and TRAF6-dependent activation of TAK1 in the absence of TAB2 and TAB3 |
title | Interleukin-1 and TRAF6-dependent activation of TAK1 in the absence of TAB2 and TAB3 |
title_full | Interleukin-1 and TRAF6-dependent activation of TAK1 in the absence of TAB2 and TAB3 |
title_fullStr | Interleukin-1 and TRAF6-dependent activation of TAK1 in the absence of TAB2 and TAB3 |
title_full_unstemmed | Interleukin-1 and TRAF6-dependent activation of TAK1 in the absence of TAB2 and TAB3 |
title_short | Interleukin-1 and TRAF6-dependent activation of TAK1 in the absence of TAB2 and TAB3 |
title_sort | interleukin-1 and traf6-dependent activation of tak1 in the absence of tab2 and tab3 |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5632801/ https://www.ncbi.nlm.nih.gov/pubmed/28507161 http://dx.doi.org/10.1042/BCJ20170288 |
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