{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nCENP‐E is a conserved kinesin‐motor protein that plays a central role in ensuring faithful chromosome segregation during mitosis. It localizes to the outer kinetochore and its activity stabilizes the capture of spindle microtubules, thereby promoting proper chromosome alignment at the metaphase plate. Loss or reduction of CENP‐E function disrupts kinetochore–microtubule attachments, leading to chromosome missegregation, cell cycle arrest, and even embryonic lethality, which in turn compromises genomic stability and can modulate tumor formation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its mitotic function, CENP‐E is critically important during meiosis. In mouse spermatocytes and oocytes, it not only localizes to kinetochores but also contributes to centromere and kinetochore reorganization that is essential for the second meiotic division. By stabilizing key spindle assembly checkpoint components and ensuring proper kinetochore orientation—even when chromosomes become displaced—CENP‐E promotes bi‐orientation and supports a checkpoint mechanism that minimizes the risk of aneuploidy during gametogenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its classical roles in cell division, aberrant expression or functional disruption of CENP‐E has been linked to pathological conditions. Elevated CENP‐E levels have been associated with hypoxia‐induced pulmonary vascular remodeling, while its depletion can trigger cell death in contexts of heightened chromosome missegregation, ultimately suppressing tumor development in certain settings. Moreover, in vivo inhibition studies in mouse spermatocytes have underscored its importance in spindle organization and chromosome stability, highlighting CENP‐E as a potential target for therapeutic intervention in diseases rooted in mitotic and meiotic defects."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Frances R Putkey, Thorsten Cramer, Mary K Morphew, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Unstable kinetochore-microtubule capture and chromosomal instability following deletion of CENP-E."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Cell (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s1534-5807(02)00255-1"}], "href": "https://doi.org/10.1016/s1534-5807(02"}, {"type": "t", "text": "00255-1) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12361599"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12361599"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Alain D Silk, Lauren M Zasadil, Andrew J Holland, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Chromosome missegregation rate predicts whether aneuploidy will promote or suppress tumors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1317042110"}], "href": "https://doi.org/10.1073/pnas.1317042110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24133140"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24133140"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "María T Parra, Jesús Page, Tim J Yen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression and behaviour of CENP-E at kinetochores during mouse spermatogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Chromosoma (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00412-002-0185-5"}], "href": "https://doi.org/10.1007/s00412-002-0185-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12068923"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12068923"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "María Teresa Parra, Rocío Gómez, Alberto Viera, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sequential assembly of centromeric proteins in male mouse meiosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1000417"}], "href": "https://doi.org/10.1371/journal.pgen.1000417"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19283064"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19283064"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Liming Gui, Hayden Homer "}, {"type": "b", "children": [{"type": "t", "text": "Spindle assembly checkpoint signalling is uncoupled from chromosomal position in mouse oocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Development (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/dev.078352"}], "href": "https://doi.org/10.1242/dev.078352"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22513372"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22513372"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Xiaoyu Fang, Min Xie, Xiansheng Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CENPE contributes to pulmonary vascular remodeling in pulmonary hypertension."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2021.04.010"}], "href": "https://doi.org/10.1016/j.bbrc.2021.04.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33862458"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33862458"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Meng-Fei Xu, Yu-Hao Yang, Ya-Lan Wei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional Assessment of Kinesin-7 CENP-E in Spermatocytes using In Vivo Inhibition, Immunofluorescence and Flow Cytometry."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Vis Exp (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3791/63271"}], "href": "https://doi.org/10.3791/63271"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35037651"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35037651"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Zhen-Yu She, Meng-Fei Xu, Sun-Ying Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Kinesin-7 CENP-E is essential for chromosome alignment and spindle assembly of mouse spermatocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Mol Cell Res (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbamcr.2022.119306"}], "href": "https://doi.org/10.1016/j.bbamcr.2022.119306"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35680098"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35680098"}]}]}]}