| First Author | Marcato V | Year | 2016 |
| Journal | Mol Cell Biol | Volume | 36 |
| Issue | 1 | Pages | 13-29 |
| PubMed ID | 26459757 | Mgi Jnum | J:235834 |
| Mgi Id | MGI:5803770 | Doi | 10.1128/MCB.00641-15 |
| Citation | Marcato V, et al. (2016) beta-Catenin Upregulates the Constitutive and Virus-Induced Transcriptional Capacity of the Interferon Beta Promoter through T-Cell Factor Binding Sites. Mol Cell Biol 36(1):13-29 |
| abstractText | Rapid upregulation of interferon beta (IFN-beta) expression following virus infection is essential to set up an efficient innate antiviral response. Biological roles related to the antiviral and immune response have also been associated with the constitutive production of IFN-beta in naive cells. However, the mechanisms capable of modulating constitutive IFN-beta expression in the absence of infection remain largely unknown. In this work, we demonstrate that inhibition of the kinase glycogen synthase kinase 3 (GSK-3) leads to the upregulation of the constitutive level of IFN-beta expression in noninfected cells, provided that GSK-3 inhibition is correlated with the binding of beta-catenin to the IFN-beta promoter. Under these conditions, IFN-beta expression occurred through the T-cell factor (TCF) binding sites present on the IFN-beta promoter independently of interferon regulatory factor 3 (IRF3). Enhancement of the constitutive level of IFN-beta per se was able to confer an efficient antiviral state to naive cells and acted in synergy with virus infection to stimulate virus-induced IFN-beta expression. Further emphasizing the role of beta-catenin in the innate antiviral response, we show here that highly pathogenic Rift Valley fever virus (RVFV) targets the Wnt/beta-catenin pathway and the formation of active TCF/beta-catenin complexes at the transcriptional and protein level in RVFV-infected cells and mice. |
