{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNuMA1, encoded by the NUMA1 gene, is a multifunctional protein central to the assembly and orientation of the mitotic spindle. In dividing cells, NuMA1 directly binds microtubules via a defined C‐terminal domain that not only mediates microtubule bundling and stabilization but also facilitates the clustering of spindle poles. Acting in concert with key partners—including dynein, dynactin, LGN, Rae1, and components of the END network—NuMA1 orchestrates the proper positioning of spindle microtubule minus ends, thereby ensuring accurate chromosome congression in both mitotic and meiotic settings. Notably, NuMA1 also undergoes liquid–liquid phase separation, a process that concentrates tubulin and critical regulatory factors at the spindle poles, and displays dynamic exchange between soluble and spindle-associated pools, partly determined by phosphorylation and interactions with transport factors."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its canonical role in spindle organization, NuMA1 contributes to crucial non‐mitotic processes. It modulates p53‐mediated transcription—selectively promoting the expression of p21 to enforce cell cycle arrest—and participates in nuclear architecture by localizing within and influencing nucleolar functions such as rDNA transcription and the cellular stress response. Furthermore, NuMA1 is an early target during apoptosis, where its caspase‐mediated cleavage facilitates the breakdown of nuclear structure."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "14", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic studies have further implicated NUMA1 in human disease. Single nucleotide polymorphisms—such as the nonsynonymous A794G variant—have been associated with altered breast cancer risk, suggesting that subtle changes in NuMA1 function may contribute to tumorigenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition, NuMA1 has been shown to interact with viral proteins; for example, its association with the Kaposi’s sarcoma–associated LANA is critical for tethering viral genomes to host chromosomes during cell division, thus ensuring faithful viral episome segregation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Angela Cox, Alison M Dunning, Montserrat Garcia-Closas, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Ric-8A and Gi alpha recruit LGN, NuMA, and dynein to the cell cortex to help orient the mitotic spindle."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00394-10"}], "href": "https://doi.org/10.1128/MCB.00394-10"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20479129"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20479129"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Agnieszka Kolano, Stéphane Brunet, Alain D Silk, et al. 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