{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSEPTIN6 was first implicated in oncogenesis as a fusion partner of MLL in infant acute myelogenous leukemia, wherein rearrangements involving SEPTIN6 contribute to leukemogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In a distinct context, SEPTIN6 has also been shown to interact with host factors that facilitate hepatitis C virus replication, as knockdown experiments revealed that disruption of SEPTIN6 can inhibit viral propagation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the structural level, SEPTIN6 is an essential component of hetero‐oligomeric septin complexes that include partners such as SEPT2 and SEPT7. High‐resolution structural studies—including X‐ray crystallography and cryo–electron microscopy—have uncovered that SEPTIN6 contributes to the formation of a universal bipolar polymer building block. These analyses demonstrate its participation in defining specific GTPase interfaces, the organization of coiled–coil domains, and the overall filament architecture that underlies septin scaffold assembly."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFunctionally, SEPTIN6 plays a critical role in maintaining cytoskeletal dynamics and cellular morphology. Experimental depletion of SEPTIN6 alongside other septins has been shown to disrupt stress fiber integrity and impair cell polarity, while its regulated assembly contributes to the directional guidance of microtubule plus-end movement and the maturation of endothelial podosomes crucial for cell invasion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSEPTIN6 further modulates intracellular signaling and membrane dynamics. For instance, its interaction with SEPT12 can alter septin filament organization, suggesting roles in cytokinesis and filament bundling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " In addition, SEPTIN6–containing complexes regulate protein sorting during multivesicular body biogenesis by coordinating the association of adaptor complexes, thereby influencing cargo selection."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Its expression is also targeted by microRNAs such as miR–223 in prostate cancer, with altered SEPTIN6 levels contributing to enhanced malignancy"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": ", and by epigenetic mechanisms—exemplified by LSD1–mediated promoter demethylation which upregulates SEPTIN6 to promote metastasis in non–small cell lung cancer."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " In hepatocellular carcinoma, SEPTIN6 fosters tumor progression through facilitation of F–actin formation and subsequent activation of the YAP signaling pathway"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": ", while in liver fibrosis, enhanced SEPTIN6 expression in hepatic stellate cells promotes extracellular matrix deposition and fibrotic remodeling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFinally, posttranslational modifications further refine SEPTIN6 function. For example, covalent modification by small ubiquitin–like modifiers (SUMOs) has been identified on septins belonging to the SEPT6 group, underscoring a pivotal regulatory mechanism for septin filament bundling and cell division."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Diana J Slater, Eva Hilgenfeld, Eric F Rappaport, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MLL-SEPTIN6 fusion recurs in novel translocation of chromosomes 3, X, and 11 in infant acute myelomonocytic leukaemia and in t(X;11) in infant acute myeloid leukaemia, and MLL genomic breakpoint in complex MLL-SEPTIN6 rearrangement is a DNA topoisomerase II cleavage site."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.onc.1205572"}], "href": "https://doi.org/10.1038/sj.onc.1205572"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12096348"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12096348"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "ShriHari S Kadkol, Annette Bruno, Steven Oh, et al. 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