| Autor: |
Zexiao Jia, Shuxu Yang, Mengyao Li, Zhaoying Lei, Xue Ding, Mingjie Fan, Dixian Wang, Dajiang Xie, Hui Zhou, Yue Qiu, Qianqian Zhuang, Dan Li, Wei Yang, Xuchen Qi, Xiaohui Cang, Jing-Wei Zhao, Wenqi Wang, Aifu Lin, Qingfeng Yan |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
iScience, Vol 25, Iss 11, Pp 105275- (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2589-0042 |
| DOI: |
10.1016/j.isci.2022.105275 |
| Popis: |
Summary: Neurofibromatosis type 2 is an autosomal dominant multiple neoplasia syndrome and is usually caused by mutations in the neurofibromin 2 (NF2) gene, which encodes a tumor suppressor and initiates the Hippo pathway. However, the mechanism by which NF2 functions in the Hippo pathway isn’t fully understood. Here we identified a NF2 c.770-784del mutation from a neurofibromatosis type 2 family. MD simulations showed that this mutation significantly changed the structure of the F3 module of the NF2-FERM domain. Functional assays indicated that the NF2 c.770-784del variant formed LLPS in the cytoplasm with LATS to restrain LATS plasma membrane localization and inactivated the Hippo pathway. Besides, this deletion partly caused a skipping of exon 8 and reduced the protein level of NF2, collectively promoting proliferation and tumorigenesis of meningeal cells. We identified an unrecognized mechanism of LLPS and splicing skipping for the NF2-induced Hippo pathway, which provided new insight into the pathogenesis of neurofibromatosis type 2. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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