{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMOS is a serine/threonine kinase whose expression is critical for proper oocyte maturation and meiotic arrest in vertebrates. In several studies, MOS was shown to be absent in immature oocytes but induced just prior to germinal vesicle breakdown, after which its activity—via the MAPK pathway and downstream effector p90rsk—leads to the phosphorylation of targets such as Erp1, thereby establishing a cytostatic factor (CSF)–mediated arrest at metaphase II until fertilization occurs."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in the meiotic divisions of oocytes, MOS has been implicated in tumorigenesis and the maintenance of genomic stability. In tetraploid cells lacking p53, upregulation of MOS inhibits the coalescence of supernumerary centrosomes, thereby fostering multipolar mitoses and the generation of aneuploid cells. Moreover, in lung adenocarcinomas with activating EGFR mutations, overexpression of MOS can substitute for EGFR signaling by activating MEK–ERK and PI3K–AKT pathways to support cell survival independently."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nEpigenetic regulation of MOS is also of clinical relevance. Studies in gastric mucosae have demonstrated that aberrant DNA methylation of the MOS gene is modulated by Helicobacter pylori infection. While H. pylori eradication may reduce MOS methylation in individuals without intestinal metaplasia, persistent or elevated methylation levels are observed in patients with gastric dysplasia or cancer, suggesting that MOS methylation may serve as a surrogate marker for prolonged exposure and heightened cancer risk."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFinally, in the context of human reproduction, a novel homozygous missense mutation in MOS has been linked to female infertility, characterized by the presence of large polar body oocytes and poor embryonic development. This mutation is thought to impair the regulation of oocyte asymmetric division through disruption of the MAPK/WAVE2/Arp2/3/actin signaling pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "H Kajiura-Kobayashi, N Yoshida, N Sagata, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Mos/MAPK pathway is involved in metaphase II arrest as a cytostatic factor but is neither necessary nor sufficient for initiating oocyte maturation in goldfish."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Genes Evol (2000)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s004270000083"}], "href": "https://doi.org/10.1007/s004270000083"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11180847"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11180847"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Daigo Inoue, Munemichi Ohe, Yoshinori Kanemori, et al. 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