Abstract
Like the type I interferons (IFNs), the recently discovered cytokine IFN-λ displays antiviral, antiproliferative, and proapoptotic activities, mediated by a heterodimeric IFN-λ receptor complex composed of a unique IFN-λR1 chain and the IL-10R2 chain. However, the molecular mechanism of the IFN-λ-regulated pathway remains unclear. In this study, we newly identified RAN-binding protein M (RanBPM) as a binding partner of IFN-λR1. The interaction between RanBPM and IFN-λR1 was identified with a glutathione S-transferase pull-down assay and coimmunoprecipitation experiments. IFN-λ1 stimulates this interaction and affects the cellular distribution of RanBPM. However, the interaction between RanBPM and IFN-λR1 does not correlate with their conserved TRAF6-binding sites. Furthermore, we also found that RanBPM is a scaffolding protein with a modulatory function that regulates the activities of IFN-stimulated response elements. Therefore, RanBPM plays a novel role in the IFN-λ-regulated signaling pathway.
Keywords:
IFN-λ; IFN-λR1; RanBPM; interaction.
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism*
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Binding Sites
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Cell Line, Transformed
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Cell Line, Tumor
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Cytoskeletal Proteins / genetics
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Cytoskeletal Proteins / metabolism*
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HEK293 Cells
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Humans
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Immunoprecipitation
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Interferon-Stimulated Gene Factor 3, gamma Subunit / metabolism
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Interferons
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Interleukins / metabolism*
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Intracellular Signaling Peptides and Proteins
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Protein Binding
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Receptors, Cytokine / genetics
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Receptors, Cytokine / metabolism*
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Receptors, Interferon
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Response Elements
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Signal Transduction / genetics
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Signal Transduction / physiology*
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TNF Receptor-Associated Factor 6 / metabolism
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Ubiquitination
Substances
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Adaptor Proteins, Signal Transducing
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Cytoskeletal Proteins
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interferon-lambda, human
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IFNLR1 protein, human
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IRF9 protein, human
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Interferon-Stimulated Gene Factor 3, gamma Subunit
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Interleukins
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Intracellular Signaling Peptides and Proteins
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Nuclear Proteins
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Ran binding protein 9
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Receptors, Cytokine
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Receptors, Interferon
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TNF Receptor-Associated Factor 6
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Tifab protein, human
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Interferons