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PMID: 11222727 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

TRADD domain of Epstein-Barr virus transforming protein LMP1 is essential for inducing immortalization and suppressing senescence of primary rodent fibroblasts.

Journal of virology ·Vol. 75 ·No. 6 ·2001-03-00 ·Pages 3010-5

Xin B, He Z, Yang X, Chan CP, Ng MH, Cao L

Abstract

Mutation analysis of latent membrane protein 1 (LMP1) in Epstein-Barr virus (EBV)-induced B-cell immortalization revealed two transformation effector sites, TES1 and TES2. TES2 mediates the interaction with tumor necrosis factor receptor-associated death domain protein (TRADD) and plays a key role in transactivating NF-kappa B and AP-1. Recombinant EBV containing LMP1 with TES2 deleted induces a limited proliferation of B cells. The present study shows that a mutant with an LMP1 site-specific mutation at TES2, LMP1(TRADD), initially stimulates cell growth and significantly extends the life span of MEF. However, it is not sufficient for the immortalization of MEF, and MEF-LMP1(TRADD) cells eventually enter growth arrest. Further analysis reveals that although LMP1(TRADD) promotes cell growth, it does not prevent the eventual onset of senescence and the expression of tumor suppressor p16(Ink4a).

MeSH Terms
Animals Cell Division Cell Transformation, Viral Cells, Cultured Cellular Senescence Cyclin-Dependent Kinase Inhibitor p16/metabolism DNA Mutational Analysis Fibroblasts Herpesvirus 4, Human/genetics,physiology Mice Protein Structure, Tertiary Proteins/chemistry,genetics,metabolism TNF Receptor-Associated Death Domain Protein TNF Receptor-Associated Factor 1 Tumor Necrosis Factor Receptor-Associated Peptides and Proteins Viral Matrix Proteins/chemistry,genetics,metabolism
Chemicals
Cyclin-Dependent Kinase Inhibitor p16 EBV-associated membrane antigen, Epstein-Barr virus Proteins TNF Receptor-Associated Death Domain Protein TNF Receptor-Associated Factor 1 Tradd protein, mouse Tumor Necrosis Factor Receptor-Associated Peptides and Proteins Viral Matrix Proteins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Xin B
Department of Microbiology, The University of Hong Kong, Hong Kong, SAR, China.
He Z
Yang X
Chan C P
Ng M H
Cao L
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.75.6.3010-3015.2001
Published
2001-03-00
Pages
3010-5
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC115928
Subset
IM
External Links
PubMed source DOI: 10.1128/JVI.75.6.3010-3015.2001 PMC Full Text View journal details
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