Interferon-induced protein with tetratricopeptide repeat 3 (IFIT3)

Interferon-induced protein with tetratricopeptide repeat 3 (IFIT3) is a cytoplasmic protein that plays a critical role in the innate immune response against viral infections. As a member of the IFIT family, it contains multiple tetratricopeptide repeat (TPR) motifs that allow it to function as a versatile scaffold, facilitating the assembly of multi-protein complexes with other IFIT members like IFIT1 and IFIT2 (UniProt, 2023). These complexes recognize and sequester viral RNA, specifically targeting 5-triphosphate RNA or non-methylated RNA to inhibit viral translation and replication (NCBI Gene, 2024). Beyond direct antiviral activity, IFIT3 modulates signaling pathways by interacting with MAVS and RIG-I, thereby amplifying the production of type I interferons. In clinical contexts, IFIT3 is frequently studied as part of the interferon signature in autoimmune diseases such as systemic lupus erythematosus and is increasingly recognized for its role in cancer (PubMed, 2019). In oncology, IFIT3 overexpression is often linked to tumor progression, metastasis, and resistance to chemotherapy in various malignancies, including pancreatic and breast cancer (Liu et al., 2011). While no direct small-molecule inhibitors of IFIT3 are currently in clinical use, it remains a significant downstream effector of interferon-based therapies and a potential target for modulating immune-related pathologies.

Other names

IFIT-3GARG-49IFI60ISG60RIG-GInterferon-induced 60 kDa proteinRetinoic acid-induced gene G protein

IFIT3 functions as a molecular scaffold that stabilizes IFIT1 and IFIT2 complexes, enabling the recognition and sequestration of viral 5-triphosphate RNA (5ppp-RNA) to prevent viral protein synthesis. It also bridges the interaction between the mitochondrial antiviral-signaling protein (MAVS) and the pattern recognition receptor RIG-I, thereby enhancing the induction of type I interferons during the innate immune response (Liu et al., 2011; UniProt, 2023).