Document Detail


Apoptosis modulation of Epstein-Barr virus-encoded latent membrane protein 1 in the epithelial cell line HeLa is stimulus-dependent.
MedLine Citation:
PMID:  12504573     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) is required for viral transformation and has been shown to protect lymphocytes from apoptosis. However, the effect of LMP1 on cells of epithelial origin remains poorly understood. Using the epithelial cell line HeLa in which the expression of LMP1 is inducibly regulated by tetracycline, we demonstrate that apoptosis triggered by ligation of the death receptor, Fas, or by the chemotherapeutic agent, etoposide, is potentiated by LMP1. Apoptosis was assessed by nuclear condensation and activation of caspase-3-like enzymes with concomitant proteolysis of the nuclear caspase substrate, poly(ADP-ribose) polymerase. However, the effect of LMP1 in HeLa cells appeared to be stimulus-dependent since apoptosis induced by tumor necrosis factor (TNF) was inhibited. Moreover, we observed an upregulation of the zinc finger protein A20 and a decrease in expression of Bcl-2 upon induction of LMP1 in HeLa cells. Taken together, these data further our understanding of the function of LMP1 in epithelial cells and suggest that LMP1, similar to its mammalian homolog CD40, can exert opposing effects on cell survival depending on the nature of the apoptosis trigger.
Authors:
Xiangning Zhang; LiFu Hu; Bengt Fadeel; Ingemar T Ernberg
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Virology     Volume:  304     ISSN:  0042-6822     ISO Abbreviation:  Virology     Publication Date:  2002 Dec 
Date Detail:
Created Date:  2002-12-30     Completed Date:  2003-05-08     Revised Date:  2008-01-09    
Medline Journal Info:
Nlm Unique ID:  0110674     Medline TA:  Virology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  330-41     Citation Subset:  IM    
Copyright Information:
Copyright 2002 Elsevier Science (USA)
Affiliation:
Microbiology and Tumor Biology Center, Karolinska Institutet, S-171 77 Stockholm, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Antigens, CD95 / physiology
Apoptosis*
Caspase 3
Caspases / physiology
Etoposide / pharmacology
Hela Cells
Humans
Intracellular Signaling Peptides and Proteins
Nasopharyngeal Neoplasms / virology
Nuclear Proteins
Protein Biosynthesis
Proteins*
Proto-Oncogene Proteins c-bcl-2 / biosynthesis
Tumor Necrosis Factor-alpha / pharmacology
Viral Matrix Proteins / physiology*
Chemical
Reg. No./Substance:
0/Antigens, CD95; 0/EBV-associated membrane antigen, Epstein-Barr virus; 0/Intracellular Signaling Peptides and Proteins; 0/Nuclear Proteins; 0/Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/Tumor Necrosis Factor-alpha; 0/Viral Matrix Proteins; 33419-42-0/Etoposide; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases; EC 6.3.2.19/TNFAIP3 protein, human

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