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SRY-Box transcription factor 9 triggers YAP nuclear entry via direct interaction in tumors

文献类型：期刊论文

作者Qian, Hui5; Ding, Chen-Hong4; Liu, Fang5; Chen, Shi-Jie3; Huang, Chen-Kai2; Xiao, Meng-Chao4; Hong, Xia-Lu5; Wang, Ming-Chen3; Yan, Fang-Zhi5; Ding, Kai5
刊名SIGNAL TRANSDUCTION AND TARGETED THERAPY
出版日期2024-04-24
卷号9期号:1页码:13
ISSN号2095-9907
DOI10.1038/s41392-024-01805-4
通讯作者Luo, Cheng(cluo@simm.ac.cn) ; Zhang, Xin(zhang68@hotmail.com) ; Xie, Wei-Fen(weifenxie@medmail.com.cn)
英文摘要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 alpha-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.
WOS关键词PROTEIN ; SOX9 ; LOCALIZATION ; PATHWAY ; YAP/TAZ ; COMPLEX ; IMPORT ; DOMAIN
资助项目National Natural Science Foundation of China (National Science Foundation of China) ; PLA assay and liver cell tracing[82072641] ; PLA assay and liver cell tracing[82030021] ; PLA assay and liver cell tracing[82070620] ; PLA assay and liver cell tracing[81802324] ; PLA assay and liver cell tracing[81703415] ; PLA assay and liver cell tracing[91853205] ; PLA assay and liver cell tracing[81900514] ; National Natural Science Foundation of China[2023YFC2507500] ; National Key R&D Program of China[21ZR1474700] ; Science and Technology Commission of Shanghai Municipality[2022279] ; Youth Innovation Promotion Association of CAS[2019B090904008] ; High-level New RD Institute[2021B0909050003] ; High-level Innovative Research Institute ; Ministry of Education Key Laboratory on Signaling Regulation and Targeting Therapy of Liver Cancer ; Shanghai Key Laboratory of Hepato-biliary Tumor Biology
WOS研究方向Biochemistry & Molecular Biology ; Cell Biology
语种英语
WOS记录号WOS:001207171800002
出版者SPRINGERNATURE
源URL[http://119.78.100.183/handle/2S10ELR8/310662]  
专题新药研究国家重点实验室
通讯作者Luo, Cheng; Zhang, Xin; Xie, Wei-Fen
作者单位1.Naval Med Univ, Clin Canc Inst, Ctr Translat Med, Shanghai, Peoples R China
2.Nanchang Univ, Affiliated Hosp 1, Dept Gastroenterol, Nanchang, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, CAS Key Lab Receptor Res,State Key Lab Drug Res, Shanghai, Peoples R China
4.Tongji Univ, Shanghai East Hosp, Sch Med, Dept Gastroenterol, Shanghai, Peoples R China
5.Naval Med Univ, Changzheng Hosp, Dept Gastroenterol, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Qian, Hui,Ding, Chen-Hong,Liu, Fang,et al. SRY-Box transcription factor 9 triggers YAP nuclear entry via direct interaction in tumors[J]. SIGNAL TRANSDUCTION AND TARGETED THERAPY,2024,9(1):13.
APA Qian, Hui.,Ding, Chen-Hong.,Liu, Fang.,Chen, Shi-Jie.,Huang, Chen-Kai.,...&Xie, Wei-Fen.(2024).SRY-Box transcription factor 9 triggers YAP nuclear entry via direct interaction in tumors.SIGNAL TRANSDUCTION AND TARGETED THERAPY,9(1),13.
MLA Qian, Hui,et al."SRY-Box transcription factor 9 triggers YAP nuclear entry via direct interaction in tumors".SIGNAL TRANSDUCTION AND TARGETED THERAPY 9.1(2024):13.

入库方式： OAI收割

来源：上海药物研究所

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