| First Author | Chathuranga WAG | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 11 | Pages | 113358 |
| PubMed ID | 37917584 | Mgi Jnum | J:347497 |
| Mgi Id | MGI:7561386 | Doi | 10.1016/j.celrep.2023.113358 |
| Citation | Chathuranga WAG, et al. (2023) Gadd45beta is critical for regulation of type I interferon signaling by facilitating G3BP-mediated stress granule formation. Cell Rep 42(11):113358 |
| abstractText | Stress granules (SGs) constitute a signaling hub that plays a critical role in type I interferon responses. Here, we report that growth arrest and DNA damage-inducible beta (Gadd45beta) act as a positive regulator of SG-mediated interferon signaling by targeting G3BP upon RNA virus infection. Gadd45beta deficiency markedly impairs SG formation and SG-mediated activation of interferon signaling in vitro. Gadd45beta knockout mice are highly susceptible to RNA virus infection, and their ability to produce interferon and cytokines is severely impaired. Specifically, Gadd45beta interacts with the RNA-binding domain of G3BP, leading to conformational expansion of G3BP1 via dissolution of its autoinhibitory electrostatic intramolecular interaction. The acidic loop 1- and RNA-binding properties of Gadd45beta markedly increase the conformational expansion and RNA-binding affinity of the G3BP1-Gadd45beta complex, thereby promoting assembly of SGs. These findings suggest a role for Gadd45beta as a component and critical regulator of G3BP1-mediated SG formation, which facilitates RLR-mediated interferon signaling. |
