| First Author | Manivasagam S | Year | 2025 |
| Journal | Cell Host Microbe | Volume | 33 |
| Issue | 4 | Pages | 512-528.e7 |
| PubMed ID | 40132591 | Mgi Jnum | J:365049 |
| Mgi Id | MGI:8174275 | Doi | 10.1016/j.chom.2025.02.017 |
| Citation | Manivasagam S, et al. (2025) Transcriptional repressor Capicua is a gatekeeper of cell-intrinsic interferon responses. Cell Host Microbe 33(4):512-528.e7 |
| abstractText | Early detection of viral infection and rapid activation of host antiviral defenses through transcriptional upregulation of interferons (IFNs) and IFN-stimulated genes (ISGs) are critical for controlling infection. However, aberrant production of IFN in the absence of viral infection leads to auto-inflammation and can be detrimental to the host. Here, we show that the DNA-binding transcriptional repressor complex composed of Capicua (CIC) and Ataxin-1 like (ATXN1L) binds to an 8-nucleotide motif near IFN and ISG promoters and prevents erroneous expression of inflammatory genes under homeostasis in humans and mice. By contrast, during respiratory viral infection, activation of the mitogen-activated protein kinase (MAPK) pathway results in rapid degradation of the CIC-ATXN1L complex, thereby relieving repression and allowing for robust induction of IFN and ISGs. Together, our studies define a new paradigm for host regulation of IFN and ISGs through the evolutionarily conserved CIC-ATXN1L transcriptional repressor complex during homeostasis and viral infection. |
