Fig. 3
From: The multiple roles of interferon regulatory factor family in health and disease
Regulation of apoptosis by IRFs. IRF-1 is a tumor suppressor and a regulatory factor of the IFN-γ system, with IFN-γ promoting the expression of IRF-1. IFN-α also induces the rapid phosphorylation and DNA-binding activity of STAT-1, followed by the accumulation of IRF-1 and IRF7. These two transcription factors bind to the TRAIL promoter and induce TRAIL expression. TRAIL is a key participant in the apoptotic pathway and plays a significant role in IFN-induced cell killing. IRF-3 is also involved in the transcriptional induction of TRAIL, where it transactivates the TRAIL promoter upon viral infection, upregulating TRAIL transcription. Conversely, IRF4 actively inhibits the transactivation mediated by IRF1. IRF3 triggers apoptosis through the RIPA pathway, which depends on the linear ubiquitination of specific lysine residues of IRF3. Within the RIPA signaling pathway, IRF3 interacts with the pro-apoptotic protein Bax to form the IRF3-Bax complex and translocates to the mitochondria, catalyzing the release of cytochrome C into the cytoplasm, subsequently activating Caspase, and ultimately leading to apoptosis. Otulin, a deubiquitinase that removes linear ubiquitin chains, inhibits RIPA by deubiquitinating IRF3 in virus-infected cells
