Simian Virus 5 V Protein Acts as an Adaptor, Linking DDB1 to STAT2, To Facilitate the Ubiquitination of STAT1
Open accessAbstract
The V protein of simian virus 5 (SV5) facilitates the ubiquitination and subsequent proteasome-mediated degradation of STAT1. Here we show, by visualizing direct protein-protein interactions and by using the yeast two-hybrid system, that while the SV5 V protein fails to bind to STAT1 directly, it binds directly and independently to both DDB1 and STAT2, two cellular proteins known to be essential for SV5-mediated degradation of STAT1. We also demonstrate that STAT1 and STAT2 interact independently of SV5 V and show that SV5 V protein acts as an adaptor molecule linking DDB1 to STAT2/STAT1 heterodimers, which in the presence of additional accessory cellular proteins, including Cullin 4a, can ubiquitinate STAT1. Additionally, we show that the avidity of STAT2 for V is relatively weak but is significantly enhanced by the presence of both STAT1 and DDB1, i.e., the complex of STAT1, STAT2, DDB1, and SV5 V is more stable than a complex of STAT2 and V. From these studies we propose a dynamic model in which SV5 V acts as a bridge, bringing together a DDB1/Cullin 4a-containing ubiquitin ligase complex and STAT1/STAT2 heterodimers, which leads to the degradation of STAT1. The loss of STAT1 results in a decrease in affinity of binding of STAT2 for V such that STAT2 either dissociates from V or is displaced from V by STAT1/STAT2 complexes, thereby ensuring the cycling of the DDB1 and SV5 V containing E3 complex for continued rounds of STAT1 ubiquitination and degradation.
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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 [99]
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- Authors
- Precious, B., Childs, K., Fitzpatrick-Swallow, V., Goodbourn, S., & Randall, R. E.
- Affiliations
- University of London (GB)
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2005-11
- Volume
- 79
- Issue
- 21
- Pages
- 13434-13441
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- PMC
- PMC1262611
- OpenAlex
- W2157111385
- Cited by
- 117
- References
- 37
- Citations by year
- 2026: 3 · 2025: 3 · 2023: 5 · 2022: 6 · 2021: 2 · 2020: 2 · 2019: 7 · 2018: 3 · 2017: 7 · 2016: 7 · 2015: 9 · 2014: 5 · 2013: 4 · 2012: 10
- FWCI
- 3.73
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Virology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- University of St Andrews
- University of Glasgow
- Biotechnology and Biological Sciences Research Council
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Keywords
- simian virus 5, V protein, STAT2, DDB1, E3 ubiquitin ligase, protein-protein interaction, proteasomal degradation, adaptor proteins, interferon signaling
- MeSH terms
- Animals, DNA-Binding Proteins, Protein Binding, Virus Replication, Signal Transduction, Trans-Activators, Viral Structural Proteins, Dimerization, Cullin Proteins, Parainfluenza Virus 5, STAT1 Transcription Factor, STAT2 Transcription Factor
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