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Basic Characteristics of Mutations
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Mutation Site
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C131R |
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Mutation Site Sentence
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Only the C131R substitution prevented pUL36 from binding and down-regulating MLKL (Fig. |
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Mutation Level
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Amino acid level |
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Mutation Type
|
Nonsynonymous substitution |
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Gene/Protein/Region
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UL36 |
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Standardized Encoding Gene
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UL36
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|
Genotype/Subtype
|
- |
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Viral Reference
|
-
|
|
Functional Impact and Mechanisms
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|
Disease
|
Cell line
|
|
Immune
|
- |
|
Target Gene
|
MLKL
|
|
Clinical and Epidemiological Correlations
|
|
Clinical Information
|
- |
|
Treatment
|
- |
|
Location
|
- |
|
Literature Information
|
|
PMID
|
32690704
|
|
Title
|
Human cytomegalovirus protein pUL36: A dual cell death pathway inhibitor
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Author
|
Fletcher-Etherington A,Nobre L,Nightingale K,Antrobus R,Nichols J,Davison AJ,Stanton RJ,Weekes MP
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Journal
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Proceedings of the National Academy of Sciences of the United States of America
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Journal Info
|
2020 Aug 4;117(31):18771-18779
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Abstract
|
Human cytomegalovirus (HCMV) is an important human pathogen and a paradigm of intrinsic, innate, and adaptive viral immune evasion. Here, we employed multiplexed tandem mass tag-based proteomics to characterize host proteins targeted for degradation late during HCMV infection. This approach revealed that mixed lineage kinase domain-like protein (MLKL), a key terminal mediator of cellular necroptosis, was rapidly and persistently degraded by the minimally passaged HCMV strain Merlin but not the extensively passaged strain AD169. The strain Merlin viral inhibitor of apoptosis pUL36 was necessary and sufficient both to degrade MLKL and to inhibit necroptosis. Furthermore, mutation of pUL36 Cys(131) abrogated MLKL degradation and restored necroptosis. As the same residue is also required for pUL36-mediated inhibition of apoptosis by preventing proteolytic activation of procaspase-8, we define pUL36 as a multifunctional inhibitor of both apoptotic and necroptotic cell death.
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Sequence Data
|
-
|