ArticleMolecular and cellular biology2009
Mammalian casein kinase 1alpha and its leishmanial ortholog regulate stability of IFNAR1 and type I interferon signaling.
Article in Molecular and cellular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 79 citations in OpenAlex.
- Review
- Characterization of the dual functions of Leishmania CK1.2 in both the parasite and the macrophage.PloS one · 2026Article
- The African swine fever virus p22 inhibits the JAK-STAT signaling pathway by promoting the TAX1BP1-mediated degradation of the type I interferon receptor.PLoS pathogens · 2025Article
- TNF-α-induced down-regulation of type I interferon receptor contributes to acquired resistance of cervical squamous cancer to Cisplatin.The Journal of antibiotics · 2024Article
- The Complexity of Interferon Signaling in Host Defense against Protozoan Parasite Infection.Pathogens (Basel, Switzerland) · 2023Review
- Targeting casein kinase 1 for cancer therapy: current strategies and future perspectives.Frontiers in oncology · 2023Review
- CK1α upregulates the IFNAR1 expression to prompt the anti-HBV effect of type I IFN in hepatoma carcinoma cells.Virologica Sinica · 2022Article
- Promastigote-to-Amastigote Conversion inPathogens (Basel, Switzerland) · 2022Review
- Structural and Functional Basis of JAMM Deubiquitinating Enzymes in Disease.Biomolecules · 2022Review
- Article
- NLRP3 phosphorylation in its LRR domain critically regulates inflammasome assembly.Nature communications · 2021Article
- Review
- Mapping immune variation andeLife · 2021Article
- Dangerous Duplicity: The Dual Functions of Casein Kinase 1 in Parasite Biology and Host Subversion.Frontiers in cellular and infection microbiology · 2021Review
- Article
- Identification of the Host Substratome ofFrontiers in cell and developmental biology · 2021Article
- Review
- PARP1 Enhances Influenza A Virus Propagation by Facilitating Degradation of Host Type I Interferon Receptor.Journal of virology · 2020Article
- Type I interferons and endoplasmic reticulum stress in health and disease.International review of cell and molecular biology · 2020Review
- Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
Abstract
Phosphorylation of the degron of the IFNAR1 chain of the type I interferon (IFN) receptor triggers ubiquitination and degradation of this receptor and, therefore, plays a crucial role in negative regulation of IFN-alpha/beta signaling. Besides the IFN-stimulated and Jak activity-dependent pathways, a basal ligand-independent phosphorylation of IFNAR1 has been described and implicated in downregulating IFNAR1 in response to virus-induced endoplasmic reticulum (ER) stress. Here we report purification and characterization of casein kinase 1alpha (CK1alpha) as a bona fide major IFNAR1 kinase that confers basal turnover of IFNAR1 and cooperates with ER stress stimuli to mediate phosphorylation-dependent degradation of IFNAR1. Activity of CK1alpha was required for phosphorylation and downregulation of IFNAR1 in response to ER stress and viral infection. While many forms of CK1 were capable of phosphorylating IFNAR1 in vitro, human CK1alpha and L-CK1 produced by the protozoan Leishmania major were also capable of increasing IFNAR1 degron phosphorylation in cells. Expression of leishmania CK1 in mammalian cells stimulated the phosphorylation-dependent downregulation of IFNAR1 and attenuated its signaling. Infection of mammalian cells with L. major modestly decreased IFNAR1 levels and attenuated cellular responses to IFN-alpha in vitro. We propose a role for mammalian and parasite CK1 enzymes in regulating IFNAR1 stability and type I IFN signaling.
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