ArticleJournal of virology2018
Transmembrane Protein pUL50 of Human Cytomegalovirus Inhibits ISGylation by Downregulating UBE1L.
Article in Journal of virology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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.
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Who cites it
21 citing papers in PubMed, 26 citations in OpenAlex.
- Organelle-centered ISG15 biology: distinguishing covalent ISGylation from interferon-associated responses.Frontiers in immunology · 2026Review
- ISGylation: is our genome yearning for such a modification?Acta biochimica et biophysica Sinica · 2025Review
- [Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- Human cytomegalovirus: pathogenesis, prevention, and treatment.Molecular biomedicine · 2024Review
- The battle between host antiviral innate immunity and immune evasion by cytomegalovirus.Cellular and molecular life sciences : CMLS · 2024Review
- Review
- Hydrogen peroxide initiates oxidative stress and proteomic alterations in meningothelial cells.Scientific reports · 2022Article
- Review
- Acute Myeloid Leukemia-Related Proteins Modified by Ubiquitin and Ubiquitin-like Proteins.International journal of molecular sciences · 2022Review
- Article
- Review
- HERC5 and the ISGylation Pathway: Critical Modulators of the Antiviral Immune Response.Viruses · 2021Review
- Viral mediated tethering to SEL1L facilitates ER-associated degradation of IRE1.Journal of virology · 2021Article
- Article
- Article
- How ISG15 combats viral infection.Virus research · 2020Review
- The Human Cytomegalovirus Transmembrane Protein pUL50 Induces Loss of VCP/p97 and Is Regulated by a Small Isoform of pUL50.Journal of virology · 2020Article
- Article
- Interferon-Independent Innate Responses to Cytomegalovirus.Frontiers in immunology · 2019Review
- Post-translational Control of Innate Immune Signaling Pathways by Herpesviruses.Frontiers in microbiology · 2019Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interferon-stimulated gene 15 (ISG15) encodes a ubiquitin-like protein that can be conjugated to proteins via an enzymatic cascade involving the E1, E2, and E3 enzymes. ISG15 expression and protein ISGylation modulate viral infection; however, the viral mechanisms regulating the function of ISG15 and ISGylation are not well understood. We recently showed that ISGylation suppresses the growth of human cytomegalovirus (HCMV) at multiple steps of the virus life cycle and that the virus-encoded pUL26 protein inhibits protein ISGylation. In this study, we demonstrate that the HCMV UL50-encoded transmembrane protein, a component of the nuclear egress complex, also inhibits ISGylation. pUL50 interacted with UBE1L, an E1-activating enzyme for ISGylation, and (to a lesser extent) with ISG15, as did pUL26. However, unlike pUL26, pUL50 caused proteasomal degradation of UBE1L. The UBE1L level induced in human fibroblast cells by interferon beta treatment or virus infection was reduced by pUL50 expression. This activity of pUL50 involved the transmembrane (TM) domain within its C-terminal region, although pUL50 could interact with UBE1L in a manner independent of the TM domain. Consistently, colocalization of pUL50 with UBE1L was observed in cells treated with a proteasome inhibitor. Furthermore, we found that RNF170, an endoplasmic reticulum (ER)-associated ubiquitin E3 ligase, interacted with pUL50 and promoted pUL50-mediated UBE1L degradation via ubiquitination. Our results demonstrate a novel role for the pUL50 transmembrane protein of HCMV in the regulation of protein ISGylation.
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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.