STAT2 is an essential adaptor in USP18-mediated suppression of type I interferon signaling
Autor(en): | Arimoto, Kei-ichiro Loechte, Sara Stoner, Samuel A. Burkart, Christoph Zhang, Yue Miyauchi, Sayuri Wilmes, Stephan Fan, Jun-Bao Heinisch, Juergen J. Li, Zhi Yan, Ming Pellegrini, Sandra Colland, Frederic Piehler, Jacob Zhang, Dong-Er |
Stichwörter: | ALPHA-INTERFERON; BINDING; Biochemistry & Molecular Biology; Biophysics; Cell Biology; GENES; IFN-LAMBDA; IMMUNE-RESPONSE; ISG15; RECEPTOR DIMERIZATION; TRANSCRIPTION; UBIQUITIN-SPECIFIC PROTEASE; UBP43 USP18 | Erscheinungsdatum: | 2017 | Herausgeber: | NATURE PUBLISHING GROUP | Journal: | NATURE STRUCTURAL & MOLECULAR BIOLOGY | Volumen: | 24 | Ausgabe: | 3 | Startseite: | 279+ | Zusammenfassung: | 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. |
ISSN: | 15459993 | DOI: | 10.1038/nsmb.3378 |
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geprüft am 04.05.2024