Protein Post‐Translational Modification‐Mediated Control of Type I Interferon Cascade Signaling

ABSTRACT Type I interferons (IFN‐Is) constitute the primary defense mechanism against pathogenic infections in the human body. The antiviral signaling mediated by IFN‐I is integral to the host immune response. Nevertheless, an imbalance in IFN‐I function can perturb the organism’s homeostasis. Consequently, it is imperative for the body to meticulously regulate the intensity and duration of the IFN‐I signaling cascade. These regulations ensure the effective execution of antiviral and antitumor functions advantageous to the host while preventing deleterious cytotoxic effects that may arise from aberrant signal activation. Post‐translational modifications (PTMs) play a crucial role in establishing a precise and dynamic regulatory network for IFN‐I signaling. Classical PTMs, including phosphorylation, ubiquitination, and acetylation, target various signaling molecules to effectively modulate the transduction of the IFN‐I signaling pathway. This review synthesizes recent advancements in understanding the regulation of IFN‐I signaling pathways by PTMs, with the aim of offering novel insights for the clinical application of IFN‐I.