STAT2 is an essential adaptor in USP18-mediated suppression of type I interferon signaling
DC Element | Wert | Sprache |
---|---|---|
dc.contributor.author | Arimoto, Kei-ichiro | |
dc.contributor.author | Loechte, Sara | |
dc.contributor.author | Stoner, Samuel A. | |
dc.contributor.author | Burkart, Christoph | |
dc.contributor.author | Zhang, Yue | |
dc.contributor.author | Miyauchi, Sayuri | |
dc.contributor.author | Wilmes, Stephan | |
dc.contributor.author | Fan, Jun-Bao | |
dc.contributor.author | Heinisch, Juergen J. | |
dc.contributor.author | Li, Zhi | |
dc.contributor.author | Yan, Ming | |
dc.contributor.author | Pellegrini, Sandra | |
dc.contributor.author | Colland, Frederic | |
dc.contributor.author | Piehler, Jacob | |
dc.contributor.author | Zhang, Dong-Er | |
dc.date.accessioned | 2021-12-23T16:23:06Z | - |
dc.date.available | 2021-12-23T16:23:06Z | - |
dc.date.issued | 2017 | |
dc.identifier.issn | 15459993 | |
dc.identifier.uri | https://osnascholar.ub.uni-osnabrueck.de/handle/unios/14419 | - |
dc.description.abstract | 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. | |
dc.description.sponsorship | NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01HL091549, R01CA177305]; DFGGerman Research Foundation (DFG)European Commission [SFB 944]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA177305] Funding Source: NIH RePORTER; NATIONAL HEART, LUNG, AND BLOOD INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Heart Lung & Blood Institute (NHLBI) [R01HL091549] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [T32GM008666] Funding Source: NIH RePORTER; We thank A. Garcia-Sastre (Icahn School of Medicine at Mount Sinai) for Stat2<SUP>-/-</SUP> MEFs, D. Cheresh (Moores UCSD Cancer Center) for MDA-MB-231, G. Stark (Cleveland Clinic) for sharing U-series cell lines, S. Fujita (Ehime University School of Medicine) for KT-1 cells, R. Xiang (The Scripps Research Institute) for WEHI-3B cells, S. Urbe (University of Liverpool) for GFP-fusion STAT2 and USP18 constructs, V. Verkhusha (Albert Einstein College of Medicine) for the mTag-BFP construct, T. Akagi (KAN Research Institute) for providing pCX4-series vectors, S. Kotenko (Rutgers New Jersey Medical School) for the pcDEF-hIFNAR2 DNA construct, D. Baker (Biogen Idec) for supplying recombinant human IFN beta and anti-human IFNAR1 antibody, the staff of Hybrigenics for their contribution, G. Hikade for technical support, and R. Kurre for advice on fluorescence microscopy. 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. | |
dc.language.iso | en | |
dc.publisher | NATURE PUBLISHING GROUP | |
dc.relation.ispartof | NATURE STRUCTURAL & MOLECULAR BIOLOGY | |
dc.subject | ALPHA-INTERFERON | |
dc.subject | BINDING | |
dc.subject | Biochemistry & Molecular Biology | |
dc.subject | Biophysics | |
dc.subject | Cell Biology | |
dc.subject | GENES | |
dc.subject | IFN-LAMBDA | |
dc.subject | IMMUNE-RESPONSE | |
dc.subject | ISG15 | |
dc.subject | RECEPTOR DIMERIZATION | |
dc.subject | TRANSCRIPTION | |
dc.subject | UBIQUITIN-SPECIFIC PROTEASE | |
dc.subject | UBP43 USP18 | |
dc.title | STAT2 is an essential adaptor in USP18-mediated suppression of type I interferon signaling | |
dc.type | journal article | |
dc.identifier.doi | 10.1038/nsmb.3378 | |
dc.identifier.isi | ISI:000395826000012 | |
dc.description.volume | 24 | |
dc.description.issue | 3 | |
dc.description.startpage | 279+ | |
dc.contributor.orcid | 0000-0003-4422-4914 | |
dc.contributor.orcid | 0000-0001-5837-7589 | |
dc.contributor.orcid | 0000-0001-5837-7589 | |
dc.contributor.orcid | 0000-0002-1709-3659 | |
dc.contributor.orcid | 0000-0002-4112-710X | |
dc.contributor.researcherid | G-3801-2017 | |
dc.contributor.researcherid | Q-4790-2018 | |
dc.contributor.researcherid | Y-6351-2019 | |
dc.contributor.researcherid | G-5546-2015 | |
dc.contributor.researcherid | E-7155-2012 | |
dc.identifier.eissn | 15459985 | |
dc.publisher.place | 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA | |
dcterms.isPartOf.abbreviation | Nat. Struct. Mol. Biol. | |
dcterms.oaStatus | Green Submitted, Green Accepted | |
crisitem.author.dept | FB 05 - Biologie/Chemie | - |
crisitem.author.deptid | fb05 | - |
crisitem.author.orcid | 0000-0002-2143-2270 | - |
crisitem.author.parentorg | Universität Osnabrück | - |
crisitem.author.netid | PiJa938 | - |
Seitenaufrufe
7
Letzte Woche
0
0
Letzter Monat
0
0
geprüft am 18.05.2024