In vitro and in vivo specificity of ubiquitination and degradation of STAT1 and STAT2 by the V proteins of the paramyxoviruses simian virus 5 and human parainfluenza virus type 2
Abstract
Previous work has documented that the V protein of simian virus 5 (SV5) targets STAT1 for proteasome-mediated degradation, whilst the V protein of human parainfluenza virus type 2 (hPIV2) targets STAT2. Here, it was shown that the processes of ubiquitination and degradation could be reconstructed in vitro by using programmed rabbit reticulocyte lysates. Using this system, the addition of bacterially expressed and purified SV5 V protein to programmed lysates was demonstrated to result in the polyubiquitination and degradation of in vitro-translated STAT1, but only if human STAT2 was also present. Surprisingly, in the same assay, purified hPIV2 V protein induced the polyubiquitination of both STAT1 and STAT2. In the light of these in vitro results, the specificity of degradation of STAT1 and STAT2 by SV5 and hPIV2 in tissue-culture cells was re-examined. As previously reported, STAT1 could not be detected in human cells that expressed SV5 V protein constitutively, whilst STAT2 could not be detected in human cells that expressed hPIV2 V protein, although the levels of STAT1 may also have been reduced in some human cells infected with hPIV2. In contrast, STAT1 could not be detected, whereas STAT2 remained present, in a variety of animal cells, including canine (MDCK) cells, that expressed the V protein of either SV5 or hPIV2. Thus, the V protein of SV5 appears to be highly specific for STAT1 degradation, but the V protein of hPIV2 is more promiscuous.
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The V protein of simian virus 5 binds the CRL4 adaptor DDB1, bringing STAT2/STAT1 heterodimers into proximity, and degradation of STAT1 diminishes interferon response.
“The V protein of simian virus 5 (SV5 V) binds the CRL4 adaptor DDB1, bringing in proximity the host STAT2/STAT1 heterodimers.Ubiquitination and further degradation of STAT1 largely diminishes interferon response to viral infection.99,100”
From Chasing molecular glue degraders: screening approaches (2022) · cites this paper as [100]
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Chasing molecular glue degraders: screening approaches
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- Authors
- Precious, B., Young, D. F., Andrejeva, L., Goodbourn, S., & Randall, R. E.
- Affiliations
- University of St Andrews (GB)
- University of London (GB)
- Venue
- Journal of General Virology
- Publisher
- Microbiology Society
- Published
- 2005-01-01
- Volume
- 86
- Issue
- 1
- Pages
- 151-158
- ISSN
- 0022-1317 (ISSN-L)
- 1465-2099
- OpenAlex
- W2132148594
- Cited by
- 56
- References
- 30
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 5 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 2 · 2014: 5 · 2013: 4 · 2012: 2
- FWCI
- 2.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of General Virology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- Biotechnology and Biological Sciences Research Council
- Topics
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- STAT1, STAT2, simian virus 5, human parainfluenza virus type 2, paramyxovirus, ubiquitination, proteasomal degradation, polyubiquitination, interferon signaling
- MeSH terms
- Animals, Cell Line, DNA-Binding Proteins, Humans, Rabbits, Reticulocytes, Species Specificity, Viral Proteins, Signal Transduction, Trans-Activators, Viral Structural Proteins, Respirovirus, Ubiquitin, STAT1 Transcription Factor, STAT2 Transcription Factor
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