The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Nonredundant and complementary functions of TRAF2 and TRAF3 in a ubiquitination cascade that activates NIK-dependent alternative NF-κB signaling
Open accessAbstract
The adaptor and signaling proteins TRAF2, TRAF3, cIAP1 and cIAP2 may inhibit alternative nuclear factor-κB (NF-κB) signaling in resting cells by targeting NF-κB–inducing kinase (NIK) for ubiquitin-dependent degradation, thus preventing processing of the NF-κB2 precursor protein p100 to release p52. However, the respective functions of TRAF2 and TRAF3 in NIK degradation and activation of alternative NF-κB signaling have remained elusive. We now show that CD40 or BAFF receptor activation result in TRAF3 degradation in a cIAP1-cIAP2- and TRAF2-dependent way owing to enhanced cIAP1, cIAP2 TRAF3-directed ubiquitin ligase activity. Receptor-induced activation of cIAP1 and cIAP2 correlated with their K63-linked ubiquitination by TRAF2. Degradation of TRAF3 prevented association of NIK with the cIAP1-cIAP2-TRAF2 ubiquitin ligase complex, which resulted in NIK stabilization and NF-κB2-p100 processing. Constitutive activation of this pathway causes perinatal lethality and lymphoid defects.
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Cites
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Cited by
Crosstalk of reactive oxygen species and NF-κB signaling
Morgan, M. J., & Liu, Z.-G. (2011) · Cell Research · doi:10.1038/cr.2010.178 · Cited by 3,505
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Self-citationCrosstalk in NF-κB Signaling Pathways
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Molecular mechanism and function of CD40/CD40L engagement in the immune system
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Metadata
- Authors
- Vallabhapurapu, S., Matsuzawa, A., Zhang, W., Tseng, P.-H., Keats, J. J., Wang, H., Vignali, D. A. A., Bergsagel, P. L., & Karin, M.
- Venue
- Nature Immunology
- Published
- 2008-11-09
- Volume
- 9
- Issue
- 12
- Pages
- 1364-1370
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W2042872424
- Cited by
- 608
- References
- 49
- FWCI
- 13.95
- Type
- journal article
- Language
- en
- Open access
- green
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- Vallabhapurapu, S., Matsuzawa, A., Zhang, W., Tseng, P.-H., Keats, J. J., Wang, H., Vignali, D. A. A., Bergsagel, P. L., & Karin, M. (2008). Nonredundant and complementary functions of TRAF2 and TRAF3 in a ubiquitination cascade that activates NIK-dependent alternative NF-κB signaling. Nature Immunology. https://doi.org/10.1038/ni.1678
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