STAT2 is an essential adaptor in USP18-mediated suppression of type I interferon signaling
Autor: | Frédéric Colland, Kei-ichiro Arimoto, Ming Yan, Dong-Er Zhang, Sandra Pellegrini, Stephan Wilmes, Yue Zhang, Jacob Piehler, Samuel A Stoner, Sayuri Miyauchi, Jürgen J. Heinisch, Sara Löchte, Christoph Burkart, Zhi Li, Jun-Bao Fan |
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Přispěvatelé: | University of California [San Diego] (UC San Diego), University of California, Fachhochschule Osnabrück, Signalisation des Cytokines - Cytokine Signaling, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hybrigenics [Paris], Hybrigenics, This study was supported by NIH R01HL091549 and R01CA177305 to D.-E.Z. and SFB 944 from the DFG to J.P. and J.J.H., University of California (UC), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Li, Zhi |
Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
MESH: Signal Transduction MESH: Interferon Type I MESH: Feedback Physiological Receptor Interferon alpha-beta Medical and Health Sciences Interferon alpha-beta MESH: Mutant Proteins Mice 0302 clinical medicine Structural Biology Interferon MESH: STAT2 Transcription Factor MESH: Animals STAT2 Receptor MESH: Endopeptidases Feedback Physiological Tumor biology MESH: Immunoblotting Effector Biological Sciences 3. Good health Cell biology 030220 oncology & carcinogenesis Interferon Type I MESH: Protein Domains Signal transduction Ubiquitin Thiolesterase medicine.drug Protein Binding Signal Transduction Cell signaling MESH: Cell Line Tumor Physiological Immunoblotting Biophysics [SDV.BC]Life Sciences [q-bio]/Cellular Biology MESH: Two-Hybrid System Techniques Article Cell Line Feedback 03 medical and health sciences Immune system Protein Domains Cell Line Tumor Two-Hybrid System Techniques Endopeptidases [SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular Biology medicine MESH: Protein Binding MESH: Receptor Interferon alpha-beta Animals Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology [SDV.BC] Life Sciences [q-bio]/Cellular Biology Molecular Biology MESH: Mice MESH: Humans STAT2 Transcription Factor 030104 developmental biology Chemical Sciences Cancer research biology.protein Mutant Proteins Interferon type I Developmental Biology |
Zdroj: | Nature structural & molecular biology Nature Structural and Molecular Biology Nature Structural and Molecular Biology, Nature Publishing Group, 2017, 24 (3), pp.279-289. ⟨10.1038/nsmb.3378⟩ Nature Structural and Molecular Biology, 2017, 24 (3), pp.279-289. ⟨10.1038/nsmb.3378⟩ Nature structural & molecular biology, vol 24, iss 3 |
ISSN: | 1545-9985 1545-9993 |
DOI: | 10.1038/nsmb.3378⟩ |
Popis: | International audience; Type I interferons (IFNs) are multifunctional cytokines that regulate immune responses and cellular functions but also can have detrimental effects on human health. A tight regulatory network therefore controls IFN signaling, which in turn may interfere with medical interventions. The JAK-STAT signaling pathway transmits the IFN extracellular signal to the nucleus, thus resulting in alterations in gene expression. STAT2 is a well-known essential and specific positive effector of type I IFN signaling. Here, we report that STAT2 is also a previously unrecognized, crucial component of the USP18-mediated negative-feedback control in both human and mouse cells. We found that STAT2 recruits USP18 to the type I IFN receptor subunit IFNAR2 via its constitutive membrane-distal STAT2-binding site. This mechanistic coupling of effector and negative-feedback functions of STAT2 may provide novel strategies for treatment of IFN-signaling-related human diseases. |
Databáze: | OpenAIRE |
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