ArticleThe EMBO journal2003
SCF(HOS) ubiquitin ligase mediates the ligand-induced down-regulation of the interferon-alpha receptor.
Article in The EMBO journal, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers.
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Who cites it
125 citing papers in PubMed, 184 citations in OpenAlex.
- Review
- Receptor dimerization enables ligand discrimination through tunable response heterogeneity.PLoS computational biology · 2025Article
- The Type I Interferon Axis in Systemic Autoimmune Diseases: From Molecular Pathways to Targeted Therapy.Biomolecules · 2025Review
- The ATR inhibitor ceralasertib potentiates cancer checkpoint immunotherapy by regulating the tumor microenvironment.Nature communications · 2024Article
- IDH1 mutation impairs antiviral response and potentiates oncolytic virotherapy in glioma.Nature communications · 2023Article
- Review
- STAM and Hrs interact sequentially with IFN-α Receptor to control spatiotemporal JAK-STAT endosomal activation.Nature cell biology · 2023Article
- Advances in the potential roles of Cullin-RING ligases in regulating autoimmune diseases.Frontiers in immunology · 2023Review
- CK1α upregulates the IFNAR1 expression to prompt the anti-HBV effect of type I IFN in hepatoma carcinoma cells.Virologica Sinica · 2022Article
- Mechanisms regulating transitory suppressive activity of neutrophils in newborns: PMNs-MDSCs in newborns.Journal of leukocyte biology · 2022Article
- Targeting PARP11 to avert immunosuppression and improve CAR T therapy in solid tumors.Nature cancer · 2022Article
- Post-transcriptional regulatory feedback encodes JAK-STAT signal memory of interferon stimulation.Frontiers in immunology · 2022Article
- UBX Domain Protein 6 Positively Regulates JAK-STAT1/2 Signaling.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Immune suppressive activity of myeloid-derived suppressor cells in cancer requires inactivation of the type I interferon pathway.Nature communications · 2021Article
- A monocentric phase I study of vemurafenib plus cobimetinib plus PEG-interferon (VEMUPLINT) in advanced melanoma patients harboring the V600BRAF mutation.Journal of translational medicine · 2021Article
- Stat2 stability regulation: an intersection between immunity and carcinogenesis.Experimental & molecular medicine · 2020Review
- Malignant cell-specific pro-tumorigenic role of type I interferon receptor in breast cancers.Cancer biology & therapy · 2020Article
- PARP1 Enhances Influenza A Virus Propagation by Facilitating Degradation of Host Type I Interferon Receptor.Journal of virology · 2020Article
- Increases in compulsivity, inflammation, and neural injury in HIV transgenic rats with escalated methamphetamine self-administration under extended-access conditions.Brain research · 2020Article
- Context Is Key: Delineating the Unique Functions of IFNα and IFNβ in Disease.Frontiers in immunology · 2020Review
65 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Down-regulation of activated signaling receptors in response to their ligands plays a key role in restricting the extent and duration of the signaling. Mechanisms underlying down-regulation of the type I interferon receptor consisting of IFNAR1 and IFNAR2 subunits remain largely unknown. Here we show that IFNAR1 interacts with the Homolog of Slimb (HOS) F-box protein in a phosphorylation-dependent manner, and that this interaction is promoted by interferon alpha (IFNalpha). IFNAR1 is ubiquitinated by the Skp1-Cullin1-HOS-Roc1 (SCF(HOS)) ubiquitin ligase in vitro. HOS expression and activities are required for IFNalpha-stimulated ubiquitination of IFNAR1, endocytosis of the type I interferon receptor, down-regulation of IFNAR1 levels, and IFNAR1 proteolysis via the lysosomal pathway. Furthermore, modulations of HOS activities affect the extent of Stat1 phosphorylation and Stat-mediated transcriptional activities as well as the extent of antiproliferative effects of type I interferons. These findings characterize SCF(HOS) as an E3 ubiquitin ligase that is essential for ubiquitination, proteolysis and down-regulation of IFNAR1, and implicate HOS in the regulation of cellular responses to IFNalpha.
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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.