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Approximately half of meningioma patients exhibit neurofibromin 2 (\n                    <jats:italic>NF2<\/jats:italic>\n                    ) gene inactivation. Here, NF2 was shown to interact with the endoplasmic reticulum (ER) calcium (Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ) channel inositol 1,4,5\u2010trisphosphate receptor 1 (IP3R1) in IOMM\u2010Lee, a high\u2010grade malignant meningioma cell line, and the F1 subdomain of NF2 plays a critical role in this interaction. Functional assays indicated that NF2 promotes the phosphorylation of IP3R (Ser 1756) and IP3R\u2010mediated endoplasmic reticulum (ER) Ca\n                    <jats:sup>2+<\/jats:sup>\n                    release by binding to IP3R1, which results in Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010dependent apoptosis. Knockout of\n                    <jats:italic>NF2<\/jats:italic>\n                    decreased Ca\n                    <jats:sup>2+<\/jats:sup>\n                    release and promoted resistance to apoptosis, which was rescued by wild\u2010type NF2 overexpression but not by F1 subdomain deletion truncation overexpression. The effects of NF2 defects on the development of tumors were further studied in mouse models. The decreased expression level of NF2 caused by\n                    <jats:italic>NF2<\/jats:italic>\n                    gene knockout or mutation affects the activity of the IP3R channel, which reduces Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010dependent apoptosis, thereby promoting the development of tumors. We elucidated the interaction patterns of NF2 and IP3R1, revealed the molecular mechanism through which NF2 regulates IP3R1\u2010mediated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    release, and elucidated the new pathogenic mechanism of meningioma\u2010related NF2 variants. Our study broadens the current understanding of the biological function of NF2 and provides ideas for drug screening of NF2\u2010associated meningioma.\n                  <\/jats:p>","DOI":"10.1096\/fj.202400436r","type":"journal-article","created":{"date-parts":[[2024,6,22]],"date-time":"2024-06-22T03:55:15Z","timestamp":1719028515000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<scp>NF2<\/scp>\n                    regulates\n                    <scp>IP3R<\/scp>\n                    \u2010mediated Ca\n                    <sup>2+<\/sup>\n                    signal and apoptosis in meningiomas"],"prefix":"10.1096","volume":"38","author":[{"given":"Zhaoying","family":"Lei","sequence":"first","affiliation":[{"name":"College of Life Sciences Zhejiang University  Hangzhou Zhejiang 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