{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMAST1, a microtubule‐associated serine/threonine kinase, plays a multifaceted role in human cancers. In breast cancer, gene fusions involving MAST1 lead to its overexpression and confer a proliferative advantage, highlighting a direct oncogenic role."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In cisplatin‐resistant tumors, MAST1 is transcriptionally upregulated through activated glucocorticoid receptor signaling and is further stabilized by interactions that prevent its ubiquitination—first via the molecular chaperone hsp90B and subsequently through USP28‐mediated deubiquitination—thereby reactivating MEK signaling and driving chemoresistance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its oncogenic functions, MAST1 is emerging as a critical regulator in neurodevelopment. De novo mutations in MAST1 have been linked to severe neurological syndromes characterized by corpus callosum malformations, cerebellar hypoplasia, and cortical malformations, underlining its essential role in the structure and function of post-mitotic neurons."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Moreover, heterozygous missense variants in MAST1 have been associated with intellectual disability, and experimental evidence in neuronal cell models implicates MAST1 in promoting neuronal differentiation via regulation of cell‐cycle arrest and the cyclin-dependent kinase inhibitor P27."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional studies have extended the relevance of MAST1 to tissue responses under stress. In gastric epithelial cells, for instance, downregulation of MAST1 after irradiation triggers growth inhibition and apoptosis through the activation of the p38 pathway, suggesting that proper MAST1 levels are vital for cell survival under radiological injury."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Furthermore, emerging evidence points to the involvement of a circular RNA derivative of MAST1 (circMAST1) in cervical cancer, hinting at an additional layer of regulation in tumor biology that warrants future investigation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Dan R Robinson, Shanker Kalyana-Sundaram, Yi-Mi Wu, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Hsp90B enhances MAST1-mediated cisplatin resistance by protecting MAST1 from proteosomal degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI125963"}], "href": "https://doi.org/10.1172/JCI125963"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31449053"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31449053"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Janardhan Keshav Karapurkar, Jencia Carminha Colaco, Bharathi Suresh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "USP28 promotes tumorigenesis and cisplatin resistance by deubiquitinating MAST1 protein in cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Life Sci (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00018-024-05187-2"}], "href": "https://doi.org/10.1007/s00018-024-05187-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38498222"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38498222"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Ratna Tripathy, Ines Leca, Tessa van Dijk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in MAST1 Cause Mega-Corpus-Callosum Syndrome with Cerebellar Hypoplasia and Cortical Malformations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuron (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuron.2018.10.044"}], "href": "https://doi.org/10.1016/j.neuron.2018.10.044"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30449657"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30449657"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Afif Ben-Mahmoud, Aisha M Al-Shamsi, Bassam R Ali, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "MAST1 modulates neuronal differentiation and cell cycle exit via P27 in neuroblastoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Open Bio (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/2211-5463.12860"}], "href": "https://doi.org/10.1002/2211-5463.12860"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32291963"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32291963"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Wenping Ding, Yuanyuan Lu, Aibin Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mast1 mediates radiation-induced gastric injury via the P38 MAPK pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2021.112913"}], "href": "https://doi.org/10.1016/j.yexcr.2021.112913"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34774870"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34774870"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Chunyu Zhang, Li Yuan, Qiaojian Zou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CircMAST1 inhibits cervical cancer progression by hindering the N4-acetylcytidine modification of YAP mRNA."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Biol Lett (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s11658-024-00540-6"}], "href": "https://doi.org/10.1186/s11658-024-00540-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38331765"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38331765"}]}]}]}