ReviewMolecular immunology2015
Identifying the ERAD ubiquitin E3 ligases for viral and cellular targeting of MHC class I.
Review in Molecular immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
33 citing papers in PubMed, 50 citations in OpenAlex.
- A viral ORFeome library for systems-level genetic dissection of host-pathogen interactions.Cell · 2026Article
- Post-translational modifications of immune checkpoints: molecular mechanisms, tumor microenvironment remodeling, and therapeutic implications.Journal of biomedical science · 2026Review
- E3 ubiquitin ligases: structural diversity, dysregulation in disease, and their emerging role in targeted therapeutic strategies.Frontiers in molecular biosciences · 2026Review
- Review
- HSV-1 UL56 protein recruits cellular NEDD4-family ubiquitin ligases to suppress CD1d expression and NKT cell function.Journal of virology · 2025Article
- MHC-I pathway disruption by viruses: insights into immune evasion and vaccine design for animals.Frontiers in immunology · 2025Review
- HCMV US2 co-opts TRC8 to degrade the endoplasmic reticulum-resident protein LMAN2L.The Journal of general virology · 2024Article
- Protein Quality Control Systems and ER Stress as Key Players in SARS-CoV-2-Induced Neurodegeneration.Cells · 2024Review
- Review
- Notch-induced endoplasmic reticulum-associated degradation governs mouse thymocyte β-selection.eLife · 2021Article
- A slowly cleaved viral signal peptide acts as a protein-integral immune evasion domain.Nature communications · 2021Article
- Viruses, cancer and non-self recognition.Open biology · 2021Review
- Targeting the ubiquitination/deubiquitination process to regulate immune checkpoint pathways.Signal transduction and targeted therapy · 2021Review
- The UFM1 Pathway Impacts HCMV US2-Mediated Degradation of HLA Class I.Molecules (Basel, Switzerland) · 2021Article
- Tight Regulation of Major Histocompatibility Complex I for the Spatial and Temporal Expression in the Hippocampal Neurons.Frontiers in cellular neuroscience · 2021Review
- Human Cytomegalovirus Host Interactions: EGFR and Host Cell Signaling Is a Point of Convergence Between Viral Infection and Functional Changes in Infected Cells.Frontiers in microbiology · 2021Review
- Article
- Oncoprotein SND1 hijacks nascent MHC-I heavy chain to ER-associated degradation, leading to impaired CD8Science advances · 2020Article
- Cellular functions and molecular mechanisms of non-lysine ubiquitination.Open biology · 2019Review
- HLA-B locus products resist degradation by the human cytomegalovirus immunoevasin US11.PLoS pathogens · 2019Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The human cytomegalovirus (HCMV) US2 and US11 gene products hijack mammalian ER-associated degradation (ERAD) to induce rapid degradation of major histocompatibility class I (MHC-I) molecules. The rate-limiting step in this pathway is thought to be the polyubiquitination of MHC-I by distinct host ERAD E3 ubiquitin ligases. TRC8 was identified as the ligase responsible for US2-mediated MHC-I degradation and shown to be required for the cleavage-dependent degradation of some tail-anchored proteins. In addition to MHC-I, plasma membrane profiling identified further immune receptors, which are also substrates for the US2/TRC8 complex. These include at least six α integrins, the coagulation factor thrombomodulin and the NK cell ligand CD112. US2's use of specific HCMV-encoded adaptors makes it an adaptable viral degradation hub. US11-mediated degradation is MHC-I-specific and genetic screens have identified TMEM129, an uncharacterised RING-C2 E3 ligase, as responsible for US11-mediated degradation. In a unique auto-regulatory loop, US11 readily responds to changes in cellular expression of MHC-I. Free US11 either rebinds more MHC-I or is itself degraded by the HRD1/SEL1L E3 ligase complex. While virally encoded US2 and US11 appropriate mammalian ERAD, the MHC-I complex also undergoes stringent cellular quality control and misfolded MHC-I is degraded by the HRD1/SEL1L complex. We discuss the identification and central role of E3 ubiquitin ligases in ER quality control and viral degradation of the MHC-I chain.
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Registered trials
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.