Unknown

Dataset Information

0

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


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.

SUBMITTER: Arimoto KI 

PROVIDER: S-EPMC5365074 | BioStudies | 2017-01-01

REPOSITORIES: biostudies

Similar Datasets

2020-01-01 | S-EPMC7201920 | BioStudies
2018-01-01 | S-EPMC6754309 | BioStudies
2015-01-01 | S-EPMC4475397 | BioStudies
2020-01-01 | S-EPMC7373899 | BioStudies
2008-01-01 | S-EPMC2494602 | BioStudies
2012-01-01 | S-EPMC3345079 | BioStudies
2019-01-01 | S-EPMC6985271 | BioStudies
2020-01-01 | S-EPMC7133002 | BioStudies
1000-01-01 | S-EPMC4321242 | BioStudies
1000-01-01 | S-EPMC4442803 | BioStudies