ArticleProceedings of the National Academy of Sciences of the United States of America2016
The adenovirus E4-ORF3 protein functions as a SUMO E3 ligase for TIF-1γ sumoylation and poly-SUMO chain elongation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 29 citations in OpenAlex.
- Review
- Nervous necrosis virus capsid protein functions as a SUMO E3 ligase to activate MAVS-dependent NF-κB signaling.Cellular and molecular life sciences : CMLS · 2026Article
- Proviral functions of HMGB1 in HAdV-C5 replication compartments.Microbiology spectrum · 2025Article
- Changes in SUMO-modified proteins in Epstein-Barr virus infection identifies reciprocal regulation of TRIM24/28/33 complexes and the lytic switch BZLF1.PLoS pathogens · 2023Article
- The interactions between PML nuclear bodies and small and medium size DNA viruses.Virology journal · 2023Review
- Contribution of Epstein-Barr Virus Lytic Proteins to Cancer Hallmarks and Implications from Other Oncoviruses.Cancers · 2023Review
- Positioning SUMO as an immunological facilitator of oncolytic viruses for high-grade glioma.Frontiers in cell and developmental biology · 2023Review
- The SUMO E3 ligase activity of ORF45 determines KSHV lytic replication.PLoS pathogens · 2022Article
- The Role of SUMO E3 Ligases in Signaling Pathway of Cancer Cells.International journal of molecular sciences · 2022Review
- SUMOylation in Viral Replication and Antiviral Defense.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Review
- Adenovirus Remodeling of the Host Proteome and Host Factors Associated with Viral Genomes.mSystems · 2021Article
- DeSUMOylation of Apoptosis Inhibitor 5 bymBio · 2021Article
- Heat Shock Protein 90 Chaperones E1A Early Protein of Adenovirus 5 and Is Essential for Replication of the Virus.International journal of molecular sciences · 2021Article
- A Tale of Usurpation and Subversion: SUMO-Dependent Integrity of Promyelocytic Leukemia Nuclear Bodies at the Crossroad of Infection and Immunity.Frontiers in cell and developmental biology · 2021Review
- ATO (Arsenic Trioxide) Effects on Promyelocytic Leukemia Nuclear Bodies Reveals Antiviral Intervention Capacity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2020Article
- Adenoviral strategies to overcome innate cellular responses to infection.FEBS letters · 2019Review
- Adenovirus E1B 55-Kilodalton Protein Targets SMARCAL1 for Degradation during Infection and Modulates Cellular DNA Replication.Journal of virology · 2019Article
- Article
- Article
- Cellular TRIM33 restrains HIV-1 infection by targeting viral integrase for proteasomal degradation.Nature communications · 2019Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The adenovirus (Ad) early region 4 (E4)-ORF3 protein regulates diverse cellular processes to optimize the host environment for the establishment of Ad replication. E4-ORF3 self-assembles into multimers to form a nuclear scaffold in infected cells and creates distinct binding interfaces for different cellular target proteins. Previous studies have shown that the Ad5 E4-ORF3 protein induces sumoylation of multiple cellular proteins and subsequent proteasomal degradation of some of them, but the detailed mechanism of E4-ORF3 function remained unknown. Here, we investigate the role of E4-ORF3 in the sumoylation process by using transcription intermediary factor (TIF)-1γ as a substrate. Remarkably, we discovered that purified E4-ORF3 protein stimulates TIF-1γ sumoylation in vitro, demonstrating that E4-ORF3 acts as a small ubiquitin-like modifier (SUMO) E3 ligase. Furthermore, E4-ORF3 significantly increases poly-SUMO3 chain formation in vitro in the absence of substrate, showing that E4-ORF3 has SUMO E4 elongase activity. An E4-ORF3 mutant, which is defective in protein multimerization, exhibited severely decreased activity, demonstrating that E4-ORF3 self-assembly is required for these activities. Using a SUMO3 mutant, K11R, we found that E4-ORF3 facilitates the initial acceptor SUMO3 conjugation to TIF-1γ as well as poly-SUMO chain elongation. The E4-ORF3 protein displays no SUMO-targeted ubiquitin ligase activity in our assay system. These studies reveal the mechanism by which E4-ORF3 targets specific cellular proteins for sumoylation and proteasomal degradation and provide significant insight into how a small viral protein can play a role as a SUMO E3 ligase and E4-like SUMO elongase to impact a variety of cellular responses.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.