{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n KIF4A is a chromokinesin motor protein that plays multiple essential roles in mitosis and beyond. In dividing cells, KIF4A localizes to chromosome arms during mitosis and is critical for proper chromosome condensation, alignment, and segregation. It functions by interacting with key microtubule‐associated factors – for example, binding to the microtubule–bundling protein PRC1 to translocate along microtubules and thereby organize the central spindle and midzone during the metaphase–anaphase transition, which is indispensable for accurate cytokinesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In addition, depletion studies have shown that loss of KIF4A leads to defective kinetochore–microtubule attachments, misalignment of chromosomes, spindle abnormalities, and ultimately errors in chromosome segregation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Post‐translational regulation also modulates KIF4A activity; for instance, Aurora B kinase phosphorylates KIF4A to stimulate its ATPase activity and to control microtubule dynamic instability during anaphase, ensuring proper spindle midzone length and function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its central mitotic role, dysregulation of KIF4A is increasingly implicated in oncogenesis. Elevated levels of KIF4A—as well as its circular RNA (circKIF4A) counterpart that functions as a competing endogenous RNA by sequestering miR-375—have been associated with enhanced proliferation, cell cycle progression (for example, via repression of p21), and activation of the spindle assembly checkpoint. Such overexpression correlates with poor prognosis in a variety of cancers including colorectal carcinoma, oral squamous cell carcinoma, and estrogen receptor–positive breast cancer."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "8"}]}, {"type": "t", "text": " \n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, KIF4A contributes to maintaining genomic stability by participating in the DNA damage response; its recruitment to DNA lesions and interaction with BRCA2 are necessary for efficient homologous recombination repair."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies reveal that KIF4A is a pivotal mediator of mitotic fidelity – ensuring proper spindle assembly, chromosome condensation, and segregation – while its aberrant expression also promotes tumor progression, making it a potential prognostic marker and therapeutic target.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yasuhiro Kurasawa, William C Earnshaw, Yuko Mochizuki, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Aurora B suppresses microtubule dynamics and limits central spindle size by locally activating KIF4A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.201301094"}], "href": "https://doi.org/10.1083/jcb.201301094"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23940115"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23940115"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Manjari Mazumdar, Suma Sundareshan, Tom Misteli "}, {"type": "b", "children": [{"type": "t", "text": "Human chromokinesin KIF4A functions in chromosome condensation and segregation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.200401142"}], "href": "https://doi.org/10.1083/jcb.200401142"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15326200"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15326200"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Ping-Fu Hou, Tao Jiang, Fang Chen, et al. 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