Abstract
Epstein-Barr virus (EBV)-encoded latent membrane protein-1 (LMP1) plays pathogenic roles in EBV-related diseases. Thus, host cells employ several mechanisms to regulate LMP1 functions, and we previously reported possible regulation by signal transducing adaptor protein-2 as well as BS69. Here, we found that caspase-3 mainly degraded LMP1 proteins in HeLa cells, leading to decreased NF-κB and STAT3 activation. Caspase-3 cleaved the consensus DNTD sequences in the CTAR3 region of LMP1. Of importance, LMP1 expression strongly enhanced caspase-3 activity. Taken together, the reduction of LMP1 protein levels by caspases is likely to be a newly identified host defense against EBV infection.
Keywords:
EBV; LMP1; NF-κB activation; caspase; degradation.
© 2016 Federation of European Biochemical Societies.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Caspase 3 / genetics
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Caspase 3 / metabolism*
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Caspase Inhibitors / pharmacology
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Enzyme Activation
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Gene Expression
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Genes, Viral
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HeLa Cells
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Herpesvirus 4, Human / genetics
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Herpesvirus 4, Human / pathogenicity
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Herpesvirus 4, Human / physiology
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Host-Pathogen Interactions
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Humans
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NF-kappa B / metabolism
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Oligopeptides / pharmacology
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Protein Structure, Tertiary
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Proteolysis
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RNA, Small Interfering / genetics
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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STAT3 Transcription Factor / metabolism
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Viral Matrix Proteins / chemistry
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Viral Matrix Proteins / genetics
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Viral Matrix Proteins / metabolism*
Substances
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Caspase Inhibitors
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EBV-associated membrane antigen, Epstein-Barr virus
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NF-kappa B
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Oligopeptides
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RNA, Small Interfering
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Recombinant Proteins
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STAT3 Transcription Factor
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STAT3 protein, human
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Viral Matrix Proteins
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benzyloxycarbonyl-valyl-alanyl-aspartic acid
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CASP3 protein, human
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Caspase 3