PMID: 8970991Dec 1, 1996Paper

Epstein-Barr virus latent membrane protein 1 blocks p53-mediated apoptosis through the induction of the A20 gene

Journal of Virology
K L FriesN Raab-Traub

Abstract

Two Epstein-Barr virus (EBV)-associated malignancies, nasopharyngeal carcinoma and posttransplant lymphoma, rarely have mutations in the p53 tumor suppressor gene, suggesting that a viral protein interferes with p53 function. The EBV oncogene, LMP1, induces expression of the cellular antiapoptotic genes bcl-2 and A20 and could in this way interfere with p53-mediated apoptosis. Two derivatives of the p53-null epithelial cell line H1299 were prepared, one of which (H1299-p53) stably expressed a temperature-sensitive (ts) p53 protein, and another (H1299-p53+LMP1) which stably expressed both ts-p53 and latent membrane protein 1 (LMP1). At the permissive temperature, the p53 protein in the H1299-p53 cell line transcriptionally activated two of its target genes, the cyclin-dependent kinase inhibitor p21 and the mdm2 gene product, in an LMP1-independent manner. Upon serum withdrawal at the permissive temperature, p53-mediated apoptosis was induced in 50 to 60% of the cells. In the H1299-p53 cell line which stably expressed LMP1, however, only 20 to 25% of the cells underwent apoptosis. While stable expression of LMP1 did not affect levels of bcl-2 family members in these cells, it did induce expression of A20. Stable expression of A20...Continue Reading

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Citations

Feb 16, 2002·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Luwen Zhang, Joseph S Pagano
Jun 10, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Neil A MarshallRobert N Barker
Mar 18, 2004·International Journal of Cancer. Journal International Du Cancer·Angela Kwok Fung LoSai-Wah Tsao
Jul 13, 2006·European Journal of Cancer Prevention : the Official Journal of the European Cancer Prevention Organisation (ECP)·Hugo SousaRui Medeiros
Mar 14, 2008·Journal of Cellular Physiology·Michael SelgradLuigi Ricciardiello
Feb 20, 2015·Journal of Virology·Roberta L TurnerDavid A Ornelles
Feb 9, 2020·Cancers·Alessia GalloPier Giulio Conaldi
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Oct 7, 2004·Journal of the National Cancer Institute·Sameek RoychowdhuryMichael A Caligiuri
Aug 22, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Andrew L SnowOlivia M Martinez
Feb 11, 2011·Journal of Virology·Che-Pei KungNancy Raab-Traub
Apr 15, 2011·Genes and Immunity·S NingG N Barber
Apr 16, 2010·Journal of Virology·Shunbin Ning, Joseph S Pagano

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