{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRab11‐FIP2 is a conserved effector of Rab11 that plays a central role in orchestrating endosomal recycling and directed membrane trafficking in polarized cells. Its C‐terminal Rab-binding domain confers specificity for Rab11, while interaction with myosin Vb enables the tethering and movement of recycling vesicles. In the context of viral infection, disruption of Rab11‐FIP2 function severely impairs the final budding step of respiratory syncytial virus, and its recruitment to Chlamydia trachomatis inclusions facilitates the diversion of nutrient-rich vesicles to support bacterial replication."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in pathogen life cycles, Rab11‐FIP2 is critical for maintaining epithelial polarity and the proper recycling of plasma membrane proteins. Phosphorylation by MARK2 at serine 227 modulates its function in reassembling cell–cell junctions, while point mutations in Rab11‐FIP2 lead to the formation of aberrant tubular endosomal structures and a delay in transcytosis. Moreover, the timely interaction with Eps15 at the lateral membrane further refines the spatial and temporal regulation required for junctional complex reestablishment."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nStructural studies reveal that the Rab-binding domain of Rab11‐FIP2 adopts a coiled-coil architecture essential for its membrane association and interaction with Rab proteins. Furthermore, its activity is subject to regulation by post-translational modifications such as ubiquitylation—mediated by ligases like RFFL—which modulates the function of Rab11-associated recycling effectors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn cancer biology, Rab11‐FIP2 exhibits context-dependent roles that influence tumor progression. In gastric cancer, its overexpression promotes epithelial–mesenchymal transition (EMT) and metastasis by modulating EGFR internalization and actin cytoskeletal dynamics."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " In colorectal carcinoma, enhanced expression of Rab11‐FIP2 correlates with increased migration and invasion through upregulation of MMP7 and activation of the PI3K/Akt pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Epigenetic mechanisms also come into play; in non-small cell lung cancer, hypermethylation-induced downregulation of Rab11‐FIP2 contributes to tumor growth by decreasing PGK1 ubiquitination and promoting oncogenic AKT/mTOR signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " In contrast, in nasopharyngeal carcinoma, elevated Rab11‐FIP2 enhances metastatic capacity by activating Rho GTPases such as Rac and Cdc42."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Andrew J Lindsay, Mary W McCaffrey "}, {"type": "b", "children": [{"type": "t", "text": "Rab11-FIP2 functions in transferrin recycling and associates with endosomal membranes via its COOH-terminal domain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M200757200"}], "href": "https://doi.org/10.1074/jbc.M200757200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11994279"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11994279"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Thomas J Utley, Nicole A Ducharme, Vasundhara Varthakavi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Respiratory syncytial virus uses a Vps4-independent budding mechanism controlled by Rab11-FIP2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0712144105"}], "href": "https://doi.org/10.1073/pnas.0712144105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18621683"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18621683"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Natalia Leiva, Anahí Capmany, María Teresa Damiani "}, {"type": "b", "children": [{"type": "t", "text": "Rab11-family of interacting protein 2 associates with chlamydial inclusions through its Rab-binding domain and promotes bacterial multiplication."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Microbiol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cmi.12035"}], "href": "https://doi.org/10.1111/cmi.12035"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23006599"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23006599"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Nicole A Ducharme, Chadwick M Hales, Lynne A Lapierre, et al. 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