IFIT3 Human

Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) is a member of the IFIT family, which includes IFIT1, IFIT2, IFIT3/4, and IFIT5. These proteins are known for their antiviral properties and are induced by interferons (IFNs), viral infections, and lipopolysaccharides (LPSs) . IFIT3, in particular, has been extensively studied for its role in various biological processes and its potential implications in cancer and immune responses.

IFIT3, like other IFIT family members, contains unique structural motifs known as tetratricopeptide repeats (TPRs). These TPRs consist of 3 to 16 tandemly repeated sequences, each comprising 34 amino acids. The TPRs are organized into helix-turn-helix configurations, which facilitate protein-protein interactions and the formation of protein complexes . Despite lacking enzymatic activity, these structural features enable IFIT3 to participate in a variety of cellular processes.

IFIT3 is primarily located in the cytoplasm and plays a crucial role in the antiviral response. It is robustly induced by type I interferons (IFNs) and is involved in the regulation of immune responses. IFIT3 has been shown to potentiate antiviral signaling by interacting with other proteins and forming complexes that enhance the immune response .

In addition to its antiviral properties, IFIT3 has been implicated in cancer progression. For instance, studies have shown that IFIT3 is highly expressed in head and neck squamous cell carcinoma (HNSC) and is associated with poorer survival outcomes . IFIT3 promotes epithelial-mesenchymal transition (EMT) and cancer stemness by targeting PD-L1 and activating the PI3K/AKT signaling pathway .

The expression of IFIT3 is tightly regulated by interferons and other signaling molecules. Upon stimulation by type I IFNs, the JAK-STAT pathway is activated, leading to the formation of the ISGF3 transcriptional complex. This complex, consisting of STAT1, STAT2, and IRF9, binds to the promoter regions of IFIT genes, including IFIT3, and induces their transcription .

The role of IFIT3 in cancer and immune responses has significant clinical implications. In cancer, targeting IFIT3 may provide a novel therapeutic strategy for treating malignancies such as HNSC. Additionally, the modulation of IFIT3 expression and its associated signaling pathways could enhance the efficacy of immunotherapies and improve patient outcomes .