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- W2318742501 abstract "Mutations in the NF2 tumor suppressor gene lead to inherited cancer-disorder Neurofibromatosis Type 2 (NF2) and other sporadic nerve-sheath tumors. Merlin, the protein product of the NF2 gene, suppresses cell proliferation and tumorigenesis by regulating multiple signaling pathways including the Ras-MAPK pathway. Through affinity purification, we have identified a novel tight-junction-associated protein complex comprising Merlin and a number of tight junction associated proteins. We show that Merlin directly interacts and co-localizes with one of these tight junction proteins through their mutual coiled-coil domains in epithelial and Schwann cells. Furthermore, the two proteins co-localize to paranodes and Schmidt-Lantermann incisures in myelinated peripheral nerve, the most frequent site of tumor development caused by Nf2 inactivation. We establish that the novel Merlin-binding protein functions downstream of Merlin as a positive regulator of Rac1 activity and the Ras-MAPK signaling. Importantly, we are able to demonstrate that depletion of this Merlin-interacting protein in Nf2-/- schwannoma cells down-regulates the Ras-MAPK signaling pathway, and impedes cellular proliferation in vitro and tumor development in vivo. Taken together with our observations that several NF2 patient-derived mutant Merlin proteins exhibit diminished association with this protein and that its level is elevated in 9 out of 10 human schwannoma samples examined, we conclude that the novel Merlin-binding partner identified in this study mediates the tumor suppressive function of Merlin and represents a potential therapeutic target for NF2 related tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1128." @default.
- W2318742501 created "2016-06-24" @default.
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- W2318742501 date "2010-04-15" @default.
- W2318742501 modified "2023-09-25" @default.
- W2318742501 title "Abstract 1128: The tumor suppressive function of Merlin/Nf2 is mediated by a novel tight junction-associated protein complex" @default.
- W2318742501 doi "https://doi.org/10.1158/1538-7445.am10-1128" @default.
- W2318742501 hasPublicationYear "2010" @default.
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