Abstract
The protein inhibitor of activated STAT1 (PIAS1), known to be a small ubiquitin-like modifier (SUMO) E3 ligase, was found to interact with the human cytomegalovirus IE2 protein. We found that the sumoylation of IE2 was markedly enhanced by wild-type PIAS1 but not by a mutant containing a Cys to Ser substitution at position 351 (C351S) within the RING finger-like domain. In target reporter gene assays, wild-type PIAS1, but not the C351S mutant, enhanced the IE2-mediated transactivations of viral polymerase promoter and cellular cyclin E promoter and this augmentation required the intact sumoylation sites of IE2. Our results suggest that PIAS1 acts as a SUMO E3 ligase toward IE2 and that it may regulate the transactivation function of IE2. To our knowledge, IE2 is the first viral target found to be regulated by a SUMO E3 ligase.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Substitution
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Animals
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Binding Sites
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Cell Line
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Cytomegalovirus / genetics
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Cytomegalovirus / metabolism*
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DNA-Directed DNA Polymerase / genetics
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DNA-Directed DNA Polymerase / metabolism
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Galactosidases / metabolism
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Genes, Reporter / genetics
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Humans
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Immediate-Early Proteins / genetics
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Immediate-Early Proteins / metabolism*
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Promoter Regions, Genetic
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Protein Inhibitors of Activated STAT
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Protein Structure, Tertiary
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Proteins / chemistry
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Proteins / genetics
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Proteins / metabolism*
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Proteins / pharmacology
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Recombinant Fusion Proteins / pharmacology
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SUMO-1 Protein / metabolism*
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Trans-Activators / metabolism*
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Transcriptional Activation
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Transfection
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Ubiquitin-Protein Ligases / metabolism
Substances
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IE2 protein, Cytomegalovirus
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Immediate-Early Proteins
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Protein Inhibitors of Activated STAT
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Proteins
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Recombinant Fusion Proteins
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SUMO-1 Protein
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Trans-Activators
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Ubiquitin-Protein Ligases
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DNA-Directed DNA Polymerase
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Galactosidases