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Journal of Virology, March 2001, p. 3010-3015, Vol. 75, No. 6
Department of Microbiology, The University of
Hong Kong, Hong Kong, SAR, China
Received 28 August 2000/Accepted 18 December 2000
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-
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.6.3010-3015.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
TRADD Domain of Epstein-Barr Virus Transforming Protein LMP1
Is Essential for Inducing Immortalization and Suppressing
Senescence of Primary Rodent Fibroblasts

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, LMP1TRADD,
initially stimulates cell growth and significantly extends the life
span of MEF. However, it is not sufficient for the immortalization of
MEF, and MEF-LMP1TRADD cells eventually enter growth
arrest. Further analysis reveals that although LMP1TRADD
promotes cell growth, it does not prevent the eventual onset of
senescence and the expression of tumor suppressor p16Ink4a.
*
Corresponding author. Mailing address: Department of
Microbiology, The University of Hong Kong, Pathology Building, Queen Mary Hospital, Hong Kong, SAR, China. Phone: 852-2855-4892. Fax: 852-2855-1241. E-mail: lcao{at}hkucc.hku.hk.
Present address: Cancer Research Institute, Hunan Medical University,
Changsha, Hunan, China.
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