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Article: Epstein-Barr virus latent membrane protein 1 activation of NF-κB through IRAK1 and TRAF6

TitleEpstein-Barr virus latent membrane protein 1 activation of NF-κB through IRAK1 and TRAF6
Authors
Issue Date2003
Citation
Proceedings of the National Academy of Sciences of the United States of America, 2003, v. 100, n. 26, p. 15595-15600 How to Cite?
AbstractEpstein-Barr virus latent membrane protein 1 (LMP1) activation of NF-κB is critical for Epstein-Barr virus-infected B lymphocyte survival. LMP1 activates the IκB kinase complex and NF-κB through two cytoplasmic signaling domains that engage tumor necrosis factor receptor-associated factor (TRAF)1/2/3/5 or TRADD and RIP. We now use cells lacking expression of TRAF2, TRAF5, TRAF6, IKKα, IKKβ, IKKγ, TAB2, IL-1 receptor-associated kinase (IRAK)1, or IRAK4 to assess their roles in LMP1-mediated NF-κB activation. LMP1-induced RelA nuclear translocation was similar in IKKα knockout (KO) and WT murine embryo fibroblasts (MEFs) but substantially deficient in IKKβ KO MEFs. NF-κB-dependent promoter responses were also substantially deficient in IKKβ KO MEFs but were hyperactive in IKKα KO MEFs. More surprisingly, NF-κB responses were near normal in TRAF2 and TRAF5 double-KO MEFs, IKKγ KO MEFs, TAB2 KO MEFs, and IRAK4 KO MEFs but were highly deficient in TRAF6 KO MEFs and IRAK1 KO HEK293 cells. Consistent with the importance of TRAF6, LMP1-induced NF-κB activation in HEK293 cells was inhibited by expression of dominant-negative TAB2 and Ubc13 alleles. These data extend a role for IKKα in IKKβ regulation, identify an unusual IKKβ-dependent and IKKγ-independent NF-κB activation, and indicate that IRAK1 and TRAF6 are essential for LMP1-induced NF-κB activation.
Persistent Identifierhttp://hdl.handle.net/10722/292225
ISSN
2023 Impact Factor: 9.4
2023 SCImago Journal Rankings: 3.737
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLuftig, Micah-
dc.contributor.authorPrinarakis, Efthimios-
dc.contributor.authorYasui, Teruhito-
dc.contributor.authorTsichritzis, Theodore-
dc.contributor.authorCahir-McFarland, Ellen-
dc.contributor.authorInoue, Jun Ichiro-
dc.contributor.authorNakano, Hiroyasu-
dc.contributor.authorMak, Tak Wah-
dc.contributor.authorYeh, Wen Chen-
dc.contributor.authorLi, Xiaoxia-
dc.contributor.authorAkira, Shizuo-
dc.contributor.authorSuzuki, Nobutaka-
dc.contributor.authorSuzuki, Shinobu-
dc.contributor.authorMosialos, George-
dc.contributor.authorKieff, Elliott-
dc.date.accessioned2020-11-17T14:56:01Z-
dc.date.available2020-11-17T14:56:01Z-
dc.date.issued2003-
dc.identifier.citationProceedings of the National Academy of Sciences of the United States of America, 2003, v. 100, n. 26, p. 15595-15600-
dc.identifier.issn0027-8424-
dc.identifier.urihttp://hdl.handle.net/10722/292225-
dc.description.abstractEpstein-Barr virus latent membrane protein 1 (LMP1) activation of NF-κB is critical for Epstein-Barr virus-infected B lymphocyte survival. LMP1 activates the IκB kinase complex and NF-κB through two cytoplasmic signaling domains that engage tumor necrosis factor receptor-associated factor (TRAF)1/2/3/5 or TRADD and RIP. We now use cells lacking expression of TRAF2, TRAF5, TRAF6, IKKα, IKKβ, IKKγ, TAB2, IL-1 receptor-associated kinase (IRAK)1, or IRAK4 to assess their roles in LMP1-mediated NF-κB activation. LMP1-induced RelA nuclear translocation was similar in IKKα knockout (KO) and WT murine embryo fibroblasts (MEFs) but substantially deficient in IKKβ KO MEFs. NF-κB-dependent promoter responses were also substantially deficient in IKKβ KO MEFs but were hyperactive in IKKα KO MEFs. More surprisingly, NF-κB responses were near normal in TRAF2 and TRAF5 double-KO MEFs, IKKγ KO MEFs, TAB2 KO MEFs, and IRAK4 KO MEFs but were highly deficient in TRAF6 KO MEFs and IRAK1 KO HEK293 cells. Consistent with the importance of TRAF6, LMP1-induced NF-κB activation in HEK293 cells was inhibited by expression of dominant-negative TAB2 and Ubc13 alleles. These data extend a role for IKKα in IKKβ regulation, identify an unusual IKKβ-dependent and IKKγ-independent NF-κB activation, and indicate that IRAK1 and TRAF6 are essential for LMP1-induced NF-κB activation.-
dc.languageeng-
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of America-
dc.titleEpstein-Barr virus latent membrane protein 1 activation of NF-κB through IRAK1 and TRAF6-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1073/pnas.2136756100-
dc.identifier.pmid14673102-
dc.identifier.pmcidPMC307613-
dc.identifier.scopuseid_2-s2.0-9144240523-
dc.identifier.volume100-
dc.identifier.issue26-
dc.identifier.spage15595-
dc.identifier.epage15600-
dc.identifier.isiWOS:000187554600057-
dc.identifier.issnl0027-8424-

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