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
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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