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Journal of Virology, March 2001, p. 3010-3015, Vol. 75, No. 6
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

Baozhong Xin, Zhimin He,dagger Xinhai Yang, Ching-Ping Chan, Mun-Hon Ng, and Liang Cao*

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-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, 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.

dagger Present address: Cancer Research Institute, Hunan Medical University, Changsha, Hunan, China.


Journal of Virology, March 2001, p. 3010-3015, Vol. 75, No. 6
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.6.3010-3015.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.



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