IFITM protein regulation and functions: Far beyond the fight against viruses

Abstract

Interferons (IFNs) are important cytokines that regulate immune responses through the activation of hundreds of genes, including interferon-induced transmembrane proteins (IFITMs). This evolutionarily conserved protein family includes five functionally active homologs in humans. Despite the high sequence homology, IFITMs vary in expression, subcellular localization and function. The initially described adhesive and antiproliferative or pro-oncogenic functions of IFITM proteins were diluted by the discovery of their antiviral properties. The large set of viruses that is inhibited by these proteins is constantly expanding, as are the possible mechanisms of action. In addition to their beneficial antiviral effects, IFITM proteins are often upregulated in a broad spectrum of cancers. IFITM proteins have been linked to most hallmarks of cancer, including tumor cell proliferation, therapeutic resistance, angiogenesis, invasion, and metastasis. Recent studies have described the involvement of IFITM proteins in antitumor immunity. This review summarizes various levels of IFITM protein regulation and the physiological and pathological functions of these proteins, with an emphasis on tumorigenesis and antitumor immunity.

The functional role of CST1 and CCL26 in asthma development

“…Several interferon‐stimulated genes linked to viral replication were downregulated in the CST1 overexpressing cells. Among those, IFITM1 (interferon‐induced transmembrane protein 1) that inhibits the viral entry via the endocytic vesicle membrane which fuses with incoming viruses 47 . Moreover, IFIT2 , inhibits viral protein production during viral mRNA translation 48 .…”

“…Among those, IFITM1 (interferon-induced transmembrane protein 1) that inhibits the viral entry via the endocytic vesicle membrane which fuses with incoming viruses. 47 Moreover, IFIT2, inhibits viral protein production during viral mRNA translation. 48 The viral replication of different RNA and DNA viruses is suppressed by RSAD2 (viperin) a radical SAM (S-adenosyl-L-methionine) enzyme, due to its interaction with cellular and viral proteins.…”

Altered Platelet-Megakaryocyte Endocytosis and Trafficking of Albumin and Fibrinogen inRUNX1Haplodeficiency

“…IFITM3 was upregulated in RUNX1- deficient HEL cells and primary MK (Figures 6E and 7C) but IFITM3 knockdown did not inhibit fibrinogen uptake (Figure S2) suggesting that in these cells it may not IFITM3-driven. IFITM3 effect see in sepsis 40 may require other interferon-induced genes as well 44,45 .…”

“…IFITMs are important effectors in innate immunity and cancer biology 44,45 and RUNX1 is a negative regulator of neutrophil cytokine production 56,57 . The IFITM3 upregulation in RUNX1 -deficient HEL cells and MK (Figures 6 and 7) is novel and maybe relevant to autoimmune manifestations 12,58 and leukemic predisposition of FPDMM.…”

“…Platelet IFITM3 mRNA levels are reported elevated in FPDMM 55 . IFITM3 is implicated in the pathogenesis of malignancies 44,45,59,60 and AML patients with high expression have worse prognosis 61 .…”