{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n KIFC3 is a minus end–directed kinesin motor that plays multifaceted roles in maintaining cytoskeletal organization, intracellular transport, and cell–cell as well as cell–tissue integrity. In epithelial cells, KIFC3 is recruited to the zonula adherens and the Golgi apparatus, where it interacts with microtubules and specific binding partners to promote junctional stability and proper organelle positioning by, for example, recruiting the deubiquitinase USP47 to suppress E‐cadherin ubiquitination (see"}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ").\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n During mitosis, KIFC3 contributes to centrosome cohesion and proper spindle assembly. It acts as a minus end–directed force generator by counteracting the pushing forces of plus end–directed motors like EG5 to prevent premature spindle formation, while also organizing the central microtubule bridge during telophase to promote efficient cytokinesis and abscission."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In neurons, KIFC3 is implicated in the organization of dendritic microtubule arrays. Its interaction with the minus end–binding protein CAMSAP2 is essential for stabilizing microtubule architecture during dendrite development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Alterations in KIFC3 expression have been linked to cancer biology. Elevated KIFC3 can confer resistance to chemotherapeutic agents such as docetaxel in breast cancer cells"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", and its dysregulated expression in hepatocellular carcinoma correlates with enhanced cell invasion and migration."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " In addition, estrogen signaling has been shown to suppress KIFC3 expression in ER‐positive breast cancers."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its roles in cell division and adhesion, KIFC3 also participates in intracellular trafficking. It mediates the translocation and proper positioning of peroxisomes to facilitate their contact with lipid droplets, a process that is critical for fasting‐induced lipolysis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the context of specialized tissues, KIFC3 is highly expressed in the retina and retinal pigment epithelium, where it localizes to photoreceptor terminals and has been considered a candidate gene for ciliopathy‐associated disorders such as Bardet–Biedl syndrome."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Similarly, in the testis, a homolog (ec‐KIFC3) is expressed during spermiogenesis and is proposed to participate in nuclear reshaping and acrosome formation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Lastly, aberrant genetic events involving KIFC3, such as a fusion with the chromatin regulator DAXX, have been implicated in the activation of the alternative lengthening of telomeres pathway in osteosarcoma."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies underscore that KIFC3 is a versatile motor protein whose functions span from regulating cytoskeletal dynamics and mitotic fidelity to mediating intracellular transport and tissue-specific processes. Its diverse roles make KIFC3 a promising target for therapeutic intervention in cancer and other diseases.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Wenxiang Meng, Yoshimi Mushika, Tetsuo Ichii, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Anchorage of microtubule minus ends to adherens junctions regulates epithelial cell-cell contacts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2008.09.040"}], "href": "https://doi.org/10.1016/j.cell.2008.09.040"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19041755"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19041755"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Kyoko Sako-Kubota, Nobutoshi Tanaka, Shigenori Nagae, et al. 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