{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T20:26:39Z","timestamp":1790022399751,"version":"4.0.1"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013898","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000}}],"reference-count":103,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R01CA228700 and R01DE033907"],"award-info":[{"award-number":["R01CA228700 and R01DE033907"]}]},{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"publisher","award":["PF-23-1144614-01-IBCD"],"award-info":[{"award-number":["PF-23-1144614-01-IBCD"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"publisher","award":["PF-24-1250090-01-IBCD"],"award-info":[{"award-number":["PF-24-1250090-01-IBCD"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007301","name":"Harvard University Center for AIDS Research","doi-asserted-by":"publisher","award":["P30 AI060354"],"award-info":[{"award-number":["P30 AI060354"]}],"id":[{"id":"10.13039\/100007301","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>The Epstein-Barr virus (EBV) oncoprotein Latent Membrane Protein 1 (LMP1) is expressed in multiple malignancies and is critical for B-cell immortalization. LMP1 constitutively activates NF-\u03baB signaling pathways, which are essential for EBV-mediated B cell transformation and for transformed B cell survival. Reverse genetic analysis revealed two LMP1 regions critical for primary human B cell immortalization, termed transformation effector site (TES) 1 and 2, which activate multiple host growth and survival pathways, in particular NF-\u03baB. Of these, only TES1 signaling is required for B-cell transformation within the first several weeks of infection. TES1 signaling is also critical for EBV-transformed lymphoblastoid B-cell survival. However, precisely how TES1 initiates NF-\u03baB signaling has remained incompletely understood. Here, we provide multiple lines of evidence that TES1 associates with cellular inhibitor of apoptosis protein 1 and 2 (cIAP1\/2) in a tumor necrosis factor associated factor 3 (TRAF3) dependent manner. TES1 signaling drives cIAP1 autoubiquitination and targets TRAF2, cIAP1 and 2 for proteasomal degradation in a TRAF3 dependent manner. Overexpression of either cIAP1 or 2 impaired LMP1 TES1-mediated non-canonical NF-\u03baB activation. Collectively, these studies suggest that LMP1 TES1 initiates non-canonical NF-\u03baB signaling distinctly from CD40 and other host immunoreceptors, thereby highlighting a therapeutic target.<\/jats:p>","DOI":"10.1371\/journal.ppat.1013898","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T18:22:28Z","timestamp":1769451748000},"page":"e1013898","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Epstein-barr virus latent membrane protein 1 targets cIAP1, cIAP2 and TRAF2 for proteasomal degradation to activate the non-canonical NF-\u03baB pathway"],"prefix":"10.1371","volume":"22","author":[{"given":"Yizhe","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunji","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bidisha","family":"Mitra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aretina","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3965-3418","authenticated-orcid":true,"given":"Benjamin 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