| First Author | Wang Z | Year | 2019 |
| Journal | Cell Rep | Volume | 26 |
| Issue | 5 | Pages | 1273-1285.e5 |
| PubMed ID | 30699354 | Mgi Jnum | J:288872 |
| Mgi Id | MGI:6431891 | Doi | 10.1016/j.celrep.2019.01.030 |
| Citation | Wang Z, et al. (2019) The EF-Hand Protein CALML6 Suppresses Antiviral Innate Immunity by Impairing IRF3 Dimerization. Cell Rep 26(5):1273-1285.e5 |
| abstractText | The transcription factor IRF3 is phosphorylated in response to viral infection, and it subsequently forms a homodimer and translocates into the nucleus to induce the transcription of genes important for antiviral immunity, such as type I interferons (IFNs). This multistep process is essential for host defense against viral infection, but its regulation remains elusive. Here, we report that the EF-hand protein calmodulin-like 6 (CALML6) directly bound to the phosphorylated serine-rich (SR) region of IRF3 and impaired its dimerization and nuclear translocation. Enforced CALML6 expression suppressed viral infection-induced production of IFN-beta and expression of IFN-stimulated genes (ISGs), whereas CALML6 deficiency had the opposite effect. In addition, impaired IFN-beta and ISG expression in bone-marrow-derived macrophages and tissues of CALML6 transgenic mice promoted viral replication. These findings identify a phosphorylation-dependent negative feedback loop that maintains the homeostasis of antiviral innate immunity. |
