In Transduced Cells, the US3 Protein Kinase of Herpes Simplex Virus 1 Precludes Activation and Induction of Apoptosis by Transfected Procaspase 3
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Published in | Journal of Virology Vol. 81; no. 19; pp. 10242 - 10248 |
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01.10.2007
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AbstractList | The U
S
3 protein kinase of herpes simplex virus 1 blocks apoptosis induced by replication-incompetent virus mutants, proapoptotic members of the Bcl-2 family of proteins, and by a variety of other agents that act at the premitochondrial level in the proapoptotic cascade. To define the role of U
S
3 in blocking apoptosis at the postmitochondrial level, we investigated the U
S
3 protein kinase in transduced cells that were either transfected with a plasmid encoding procaspase 3 or superinfected with a proapoptotic mutant virus lacking the gene encoding the infected cell protein no. 4. (i) We show that U
S
3 blocks the proteolytic cleavage that generates active caspase 3 from the transfected zymogen procaspase 3, concomitant with inhibition of apoptosis. (ii) Studies based on detection of fluorescence emitted upon cleavage of a synthetic caspase 3 substrate showed that expression of the U
S
3 kinase and appearance of the cleaved substrate were mutually exclusive. (iii) An affinity-purified glutathione
S
-transferase (GST)-U
S
3 fusion protein, but not the inactive GST-U
S
3(K220N) protein, phosphorylated procaspase 3 in vitro. The studies published earlier on the effect of U
S
3 on the upstream regulatory proteins and current studies suggest that the U
S
3 protein kinase may act on several proteins in the proapoptotic cascade to enable the virus to complete its replication. Article Usage Stats Services JVI Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue Spotlights in the Current Issue JVI About JVI Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy JVI RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0022-538X Online ISSN: 1098-5514 Copyright © 2014 by the American Society for Microbiology. For an alternate route to JVI .asm.org, visit: JVI The US3 protein kinase of herpes simplex virus 1 blocks apoptosis induced by replication-incompetent virus mutants, proapoptotic members of the Bcl-2 family of proteins, and by a variety of other agents that act at the premitochondrial level in the proapoptotic cascade. To define the role of US3 in blocking apoptosis at the postmitochondrial level, we investigated the US3 protein kinase in transduced cells that were either transfected with a plasmid encoding procaspase 3 or superinfected with a proapoptotic mutant virus lacking the gene encoding the infected cell protein no. 4. (i) We show that US3 blocks the proteolytic cleavage that generates active caspase 3 from the transfected zymogen procaspase 3, concomitant with inhibition of apoptosis. (ii) Studies based on detection of fluorescence emitted upon cleavage of a synthetic caspase 3 substrate showed that expression of the US3 kinase and appearance of the cleaved substrate were mutually exclusive. (iii) An affinity-purified glutathione S-transferase (GST)-US3 fusion protein, but not the inactive GST-US3(K220N) protein, phosphorylated procaspase 3 in vitro. The studies published earlier on the effect of US3 on the upstream regulatory proteins and current studies suggest that the US3 protein kinase may act on several proteins in the proapoptotic cascade to enable the virus to complete its replication. |
Author | Luca Benetti Bernard Roizman |
AuthorAffiliation | Marjorie B. Kovler Viral Oncology Laboratories, University of Chicago, Chicago, Illinois 60637 |
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Keywords | Enzyme Induction Herpesviridae Transferases Alphaherpesvirinae In vitro Virology Virus Signal transduction Cell death Protein kinase Human herpesvirus 1 Apoptosis |
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Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Corresponding author. Mailing address: The Marjorie B. Kovler Viral Oncology Laboratories, The University of Chicago, 910 East 58th Street, Chicago, IL 60637. Phone: (773) 702-1898. Fax: (773) 702-1631. E-mail: bernard.roizman@bsd.uchicago.edu |
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Mendeley... The US3 protein kinase of herpes simplex virus 1 blocks apoptosis induced by replication-incompetent virus mutants, proapoptotic members of the Bcl-2 family of... The U S 3 protein kinase of herpes simplex virus 1 blocks apoptosis induced by replication-incompetent virus mutants, proapoptotic members of the Bcl-2 family... |
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SubjectTerms | Animals Apoptosis Biological and medical sciences Caspase 3 - genetics Caspase 3 - metabolism Caspase Inhibitors Cell Line, Tumor Enzyme Induction Fundamental and applied biological sciences. Psychology Humans Microbiology Miscellaneous Phosphorylation Protein-Serine-Threonine Kinases - genetics Protein-Serine-Threonine Kinases - metabolism Transduction, Genetic Transfection Viral Proteins - genetics Viral Proteins - metabolism Virology Virus-Cell Interactions |
Title | In Transduced Cells, the US3 Protein Kinase of Herpes Simplex Virus 1 Precludes Activation and Induction of Apoptosis by Transfected Procaspase 3 |
URI | http://jvi.asm.org/content/81/19/10242.abstract https://www.ncbi.nlm.nih.gov/pubmed/17634220 https://search.proquest.com/docview/68274685 https://pubmed.ncbi.nlm.nih.gov/PMC2045497 |
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