Bibliographic Details
| Title: |
SRY-Box transcription factor 9 triggers YAP nuclear entry via direct interaction in tumors |
| Authors: |
Hui Qian, Chen-Hong Ding, Fang Liu, Shi-Jie Chen, Chen-Kai Huang, Meng-Chao Xiao, Xia-Lu Hong, Ming-Chen Wang, Fang-Zhi Yan, Kai Ding, Ya-Lu Cui, Bai-Nan Zheng, Jin Ding, Cheng Luo, Xin Zhang, Wei-Fen Xie |
| Source: |
Signal Transduction and Targeted Therapy, Vol 9, Iss 1, Pp 1-13 (2024) |
| Publisher Information: |
Nature Publishing Group, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Medicine
LCC:Biology (General) |
| Subject Terms: |
Medicine, Biology (General), QH301-705.5 |
| More Details: |
Abstract The translocation of YAP from the cytoplasm to the nucleus is critical for its activation and plays a key role in tumor progression. However, the precise molecular mechanisms governing the nuclear import of YAP are not fully understood. In this study, we have uncovered a crucial role of SOX9 in the activation of YAP. SOX9 promotes the nuclear translocation of YAP by direct interaction. Importantly, we have identified that the binding between Asp-125 of SOX9 and Arg-124 of YAP is essential for SOX9-YAP interaction and subsequent nuclear entry of YAP. Additionally, we have discovered a novel asymmetrical dimethylation of YAP at Arg-124 (YAP-R124me2a) catalyzed by PRMT1. YAP-R124me2a enhances the interaction between YAP and SOX9 and is associated with poor prognosis in multiple cancers. Furthermore, we disrupted the interaction between SOX9 and YAP using a competitive peptide, S-A1, which mimics an α-helix of SOX9 containing Asp-125. S-A1 significantly inhibits YAP nuclear translocation and effectively suppresses tumor growth. This study provides the first evidence of SOX9 as a pivotal regulator driving YAP nuclear translocation and presents a potential therapeutic strategy for YAP-driven human cancers by targeting SOX9-YAP interaction. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2059-3635 |
| Relation: |
https://doaj.org/toc/2059-3635 |
| DOI: |
10.1038/s41392-024-01805-4 |
| Access URL: |
https://doaj.org/article/cc95ff42b3c84cd6a0cf53496f64f164 |
| Accession Number: |
edsdoj.95ff42b3c84cd6a0cf53496f64f164 |
| Database: |
Directory of Open Access Journals |
