2. Academic Validation
  3. STAT2 is an essential adaptor in USP18-mediated suppression of type I interferon signaling

STAT2 is an essential adaptor in USP18-mediated suppression of type I interferon signaling

  • Nat Struct Mol Biol. 2017 Mar;24(3):279-289. doi: 10.1038/nsmb.3378.
Kei-Ichiro Arimoto 1,  Sara Löchte 2,  Samuel A Stoner 1,  Christoph Burkart 1,  Yue Zhang 3,  Sayuri Miyauchi 1,  Stephan Wilmes 2,  Jun-Bao Fan 1,  Jürgen J Heinisch 2,  Zhi Li 4,  Ming Yan 1,  Sandra Pellegrini 4,  Frédéric Colland 5,  Jacob Piehler 2,  Dong-Er Zhang 1 3 6
Affiliations

Affiliations

  • 1 Moores UCSD Cancer Center, University of California San Diego, La Jolla, California, USA.
  • 2 Department of Biology, University of Osnabrück, Osnabrück, Germany.
  • 3 Division of Biological Sciences, University of California San Diego, La Jolla, California, USA.
  • 4 Institut Pasteur, Cytokine Signaling Unit, Inserm, Paris, France.
  • 5 Hybrigenics, impasse Reille, Paris, France.
  • 6 Department of Pathology, University of California San Diego, La Jolla, California, USA.
PMID: 28165510 DOI: 10.1038/nsmb.3378
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.

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