Interaction of the TNFR-receptor associated factor TRAF1 with I-kappa B kinase-2 and TRAF2 indicates a regulatory function for NF-kappa B signaling.
<h4>Background</h4>I-kappa B kinase 2 (IKK2 or IKK-beta) is one of the most crucial signaling kinases for activation of NF-kappa B, a transcription factor that is important for inflammation, cell survival and differentiation. Since many NF-kappa B activating pathways converge at the leve...
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Public Library of Science (PLoS)
2010-09-01
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| Series: | PLoS ONE |
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| author | Kalsoom Sughra Andreas Birbach Rainer de Martin Johannes A Schmid |
| author_facet | Kalsoom Sughra Andreas Birbach Rainer de Martin Johannes A Schmid |
| author_sort | Kalsoom Sughra |
| collection | DOAJ |
| description | <h4>Background</h4>I-kappa B kinase 2 (IKK2 or IKK-beta) is one of the most crucial signaling kinases for activation of NF-kappa B, a transcription factor that is important for inflammation, cell survival and differentiation. Since many NF-kappa B activating pathways converge at the level of IKK2, molecular interactions of this kinase are pivotal for regulation of NF-kappa B signaling.<h4>Methodology/principal findings</h4>We searched for proteins interacting with IKK2 using the C-terminal part (amino acids 466-756) as bait in a yeast two-hybrid system and identified the N-terminal part (amino acids 1-228) of the TNF-receptor associated factor TRAF1 as putative interaction partner. The interaction was confirmed in human cells by mammalian two-hybrid and coimmunoprecipitation experiments. The IKK2/TRAF1 interaction seemed weaker than the interaction between TRAF1 and TRAF2, an important activating adapter molecule of NF-kappa B signaling. Reporter gene and kinase assays using ectopic expression of TRAF1 indicated that it can both activate and inhibit IKK2 and NF-kappa B. Co-expression of fluorescently tagged TRAF1 and TRAF2 at different ratios implied that TRAF1 can affect clustering and presumably the activating function of TRAF2 in a dose dependent manner.<h4>Conclusions/significance</h4>The observation that TRAF1 can either activate or inhibit the NF-kappa B pathway and the fact that it influences the oligomerization of TRAF2 indicates that relative levels of IKK2, TRAF1 and TRAF2 may be important for regulation of NF-kappa B activity. Since TRAF1 is an NF-kappa B induced gene, it might act as a feedback effector molecule. |
| format | Article |
| id | doaj-art-e535309dbe7243d09dac91b9991d971d |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2010-09-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-e535309dbe7243d09dac91b9991d971d2025-08-20T02:01:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-09-0159e1268310.1371/journal.pone.0012683Interaction of the TNFR-receptor associated factor TRAF1 with I-kappa B kinase-2 and TRAF2 indicates a regulatory function for NF-kappa B signaling.Kalsoom SughraAndreas BirbachRainer de MartinJohannes A Schmid<h4>Background</h4>I-kappa B kinase 2 (IKK2 or IKK-beta) is one of the most crucial signaling kinases for activation of NF-kappa B, a transcription factor that is important for inflammation, cell survival and differentiation. Since many NF-kappa B activating pathways converge at the level of IKK2, molecular interactions of this kinase are pivotal for regulation of NF-kappa B signaling.<h4>Methodology/principal findings</h4>We searched for proteins interacting with IKK2 using the C-terminal part (amino acids 466-756) as bait in a yeast two-hybrid system and identified the N-terminal part (amino acids 1-228) of the TNF-receptor associated factor TRAF1 as putative interaction partner. The interaction was confirmed in human cells by mammalian two-hybrid and coimmunoprecipitation experiments. The IKK2/TRAF1 interaction seemed weaker than the interaction between TRAF1 and TRAF2, an important activating adapter molecule of NF-kappa B signaling. Reporter gene and kinase assays using ectopic expression of TRAF1 indicated that it can both activate and inhibit IKK2 and NF-kappa B. Co-expression of fluorescently tagged TRAF1 and TRAF2 at different ratios implied that TRAF1 can affect clustering and presumably the activating function of TRAF2 in a dose dependent manner.<h4>Conclusions/significance</h4>The observation that TRAF1 can either activate or inhibit the NF-kappa B pathway and the fact that it influences the oligomerization of TRAF2 indicates that relative levels of IKK2, TRAF1 and TRAF2 may be important for regulation of NF-kappa B activity. Since TRAF1 is an NF-kappa B induced gene, it might act as a feedback effector molecule.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0012683&type=printable |
| spellingShingle | Kalsoom Sughra Andreas Birbach Rainer de Martin Johannes A Schmid Interaction of the TNFR-receptor associated factor TRAF1 with I-kappa B kinase-2 and TRAF2 indicates a regulatory function for NF-kappa B signaling. PLoS ONE |
| title | Interaction of the TNFR-receptor associated factor TRAF1 with I-kappa B kinase-2 and TRAF2 indicates a regulatory function for NF-kappa B signaling. |
| title_full | Interaction of the TNFR-receptor associated factor TRAF1 with I-kappa B kinase-2 and TRAF2 indicates a regulatory function for NF-kappa B signaling. |
| title_fullStr | Interaction of the TNFR-receptor associated factor TRAF1 with I-kappa B kinase-2 and TRAF2 indicates a regulatory function for NF-kappa B signaling. |
| title_full_unstemmed | Interaction of the TNFR-receptor associated factor TRAF1 with I-kappa B kinase-2 and TRAF2 indicates a regulatory function for NF-kappa B signaling. |
| title_short | Interaction of the TNFR-receptor associated factor TRAF1 with I-kappa B kinase-2 and TRAF2 indicates a regulatory function for NF-kappa B signaling. |
| title_sort | interaction of the tnfr receptor associated factor traf1 with i kappa b kinase 2 and traf2 indicates a regulatory function for nf kappa b signaling |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0012683&type=printable |
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