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PMID: 10409763 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

The Epstein-Barr virus oncoprotein latent membrane protein 1 engages the tumor necrosis factor receptor-associated proteins TRADD and receptor-interacting protein (RIP) but does not induce apoptosis or require RIP for NF-kappaB activation.

Molecular and cellular biology ·Vol. 19 ·No. 8 ·1999-08-00 ·Pages 5759-67

Izumi KM, Cahir McFarland ED, Ting AT, Riley EA, Seed B, Kieff ED

Abstract

A site in the Epstein-Barr virus (EBV) transforming protein LMP1 that constitutively associates with the tumor necrosis factor receptor 1 (TNFR1)-associated death domain protein TRADD to mediate NF-kappaB and c-Jun N-terminal kinase activation is critical for long-term lymphoblastoid cell proliferation. We now find that LMP1 signaling through TRADD differs from TNFR1 signaling through TRADD. LMP1 needs only 11 amino acids to activate NF-kappaB or synergize with TRADD in NF-kappaB activation, while TNFR1 requires approximately 70 residues. Further, LMP1 does not require TRADD residues 294 to 312 for NF-kappaB activation, while TNFR1 requires TRADD residues 296 to 302. LMP1 is partially blocked for NF-kappaB activation by a TRADD mutant consisting of residues 122 to 293. Unlike TNFR1, LMP1 can interact directly with receptor-interacting protein (RIP) and stably associates with RIP in EBV-transformed lymphoblastoid cell lines. Surprisingly, LMP1 does not require RIP for NF-kappaB activation. Despite constitutive association with TRADD or RIP, LMP1 does not induce apoptosis in EBV-negative Burkitt lymphoma or human embryonic kidney 293 cells. These results add a different perspective to the molecular interactions through which LMP1, TRADD, and RIP participate in B-lymphocyte activation and growth.

MeSH Terms
Antigens, CD/physiology Apoptosis B-Lymphocytes/metabolism,pathology Burkitt Lymphoma/pathology Calcium-Calmodulin-Dependent Protein Kinases/physiology Cell Line, Transformed Cell Transformation, Viral Gene Expression Regulation Herpesvirus 4, Human/physiology Humans JNK Mitogen-Activated Protein Kinases Jurkat Cells/metabolism,pathology Kidney Macromolecular Substances Mitogen-Activated Protein Kinases Models, Molecular NF-kappa B/metabolism Proteins/metabolism Receptor-Interacting Protein Serine-Threonine Kinases Receptors, Tumor Necrosis Factor/physiology Receptors, Tumor Necrosis Factor, Type I TNF Receptor-Associated Factor 1 Transcription, Genetic Tumor Cells, Cultured Viral Matrix Proteins/physiology
Chemicals
Antigens, CD EBV-associated membrane antigen, Epstein-Barr virus Macromolecular Substances NF-kappa B Proteins Receptors, Tumor Necrosis Factor Receptors, Tumor Necrosis Factor, Type I TNF Receptor-Associated Factor 1 Viral Matrix Proteins RIPK1 protein, human Receptor-Interacting Protein Serine-Threonine Kinases Calcium-Calmodulin-Dependent Protein Kinases JNK Mitogen-Activated Protein Kinases Mitogen-Activated Protein Kinases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Izumi K M
Department of Medicine, Brigham and Women's Hospital, and Channing Laboratories, Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115-5804, USA.
Cahir McFarland E D
Ting A T
Riley E A
Seed B
Kieff E D
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.19.8.5759
Published
1999-08-00
Pages
5759-67
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC84426
Subset
IM
Grants
NCI NIH HHS · R01 CA047006 · United States
NCI NIH HHS · R35 CA047006 · United States
NCI NIH HHS · CA47006 · United States
External Links
PubMed source DOI: 10.1128/MCB.19.8.5759 PMC Full Text View journal details
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