{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMARCHF1 (also known as MARCH1) is a membrane‐anchored E3 ubiquitin ligase with a central role in immune regulation. In antigen‐presenting cells such as dendritic cells and monocytes, MARCHF1 ubiquitinates key cell surface molecules—including major histocompatibility complex class II (MHC‐II) and costimulatory molecules like CD86—thereby promoting their internalization and turnover. In resting cells, this activity limits antigen presentation, whereas signals such as Toll‐like receptor activation or IL‑10 exposure result in downregulation of MARCHF1 expression (or activity), thus stabilizing MHC‑II complexes and modulating immune responses. Additional studies describe that MARCHF1 itself is tightly regulated by ubiquitination and dimerization processes that control its protein stability and trafficking within the cell."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its immunological functions, MARCHF1 exerts influence on metabolic and oncogenic pathways. It has been shown to ubiquitinate the insulin receptor under basal conditions, thereby reducing its cell surface levels and impairing insulin signalling—a mechanism linked to insulin resistance and type 2 diabetes. In parallel, overexpression of MARCHF1 in various cancers (including ovarian, hepatocellular, and colorectal carcinomas) promotes cell proliferation, migration, and invasion by upregulating signaling cascades such as NF‑κB, PI3K‑AKT, and Wnt/β‑catenin, implicating MARCHF1 as a potential oncogene and therapeutic target."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition, MARCHF1 contributes to the cellular antiviral response and regulation of other membrane proteins. Studies have demonstrated that, similar to other MARCH family members, MARCHF1 can interfere with viral glycoprotein processing and incorporation into progeny virions, thereby reducing viral infectivity. Moreover, by indirectly modulating proteins such as the transferrin receptor, MARCHF1 plays a role in the regulation of iron metabolism—a function crucial during infections. Emerging evidence also suggests that MARCHF1 may target intracellular mediators such as TBK1, linking it further to the modulation of mTOR signalling pathways during viral infections."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Aude De Gassart, Voahirana Camosseto, Jacques Thibodeau, et al. 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