| First Author | Arimoto KI | Year | 2017 |
| Journal | Nat Struct Mol Biol | Volume | 24 |
| Issue | 3 | Pages | 279-289 |
| PubMed ID | 28165510 | Mgi Jnum | J:302465 |
| Mgi Id | MGI:6508512 | Doi | 10.1038/nsmb.3378 |
| Citation | Arimoto KI, et al. (2017) STAT2 is an essential adaptor in USP18-mediated suppression of type I interferon signaling. Nat Struct Mol Biol 24(3):279-289 |
| abstractText | 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. |
