| First Author | Zuo Y | Year | 2022 |
| Journal | Sci Adv | Volume | 8 |
| Issue | 14 | Pages | eabj3887 |
| PubMed ID | 35394840 | Mgi Jnum | J:339141 |
| Mgi Id | MGI:7263994 | Doi | 10.1126/sciadv.abj3887 |
| Citation | Zuo Y, et al. (2022) LATS1 is a central signal transmitter for achieving full type-I interferon activity. Sci Adv 8(14):eabj3887 |
| abstractText | Interferons (IFNs) have broad-spectrum antiviral activity to resist virus epidemic. However, IFN antiviral efficacy needs to be greatly improved. Here, we reveal that LATS1 is a vital signal transmitter governing full type-I IFN (IFN-I) signaling activity. LATS1 constitutively binds with the IFN-I receptor IFNAR2 and is rapidly tyro-phosphorylated by Tyk2 upon IFN-I engagement. Tyro-phosphorylation of LATS1 promotes LATS1 activation and YAP degradation, thereby promoting IFN-mediated antiproliferation activity. Moreover, activated LATS1 translocates into the nucleus and induces CDK8-Ser62 phosphorylation, which in turn phosphorylates STAT1 at Ser(727) and induces full IFN-I antiviral activity. LATS1 deficiency restricts in vivo IFN-I signaling and attenuates host antiviral immune response. Our study identifies IFN-I as a previously unidentified extracellular diffusible ligand signal for activation of the Hippo core LATS1 pathway and reveals Tyk2-LATS1-CDK8 as a complete signaling cascade controlling full IFN-I activity. |
