The mechanism of YAP/TAZ transactivation and dual targeting for cancer therapy
文献类型：期刊论文
| 作者 | Yu, Man3,4; Wang, Jingning4,5; Zhang, Xiao3,4; Zhang, Haoran4,5; Li, Chaoqiang6; Li, Juebei3,4; Lin, Jiaming3,4; Zheng, Jie6,7; Huang, Liu1; Li, Yan2,4,5 |
| 刊名 | NATURE COMMUNICATIONS
 |
| 出版日期 | 2025-04-24 |
| 卷号 | 16期号:1页码:20 |
| DOI | 10.1038/s41467-025-59309-w |
| 通讯作者 | Li, Yan(yanli@hust.edu.cn) ; Sun, Shuguo(shuguo@hust.edu.cn) |
| 英文摘要 | Transcriptional coactivators Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) play key roles in cancers through transcriptional outputs. However, their transactivation mechanisms remain unclear, and effective targeting strategies are lacking. Here, we show that YAP/TAZ possess a hydrophobic transactivation domain (TAD). TAD knockout prevents tumor establishment due to growth defects and enhances immune attack. Mechanistically, TADs facilitate preinitiation complex (PIC) assembly by recruiting the TATA-binding protein-associated factor 4 (TAF4)-dependent TFIID complex and enhance RNA polymerase II (Pol II) elongation through mediator complex subunit 15 (MED15)-dependent mediator recruitment for the expressions of oncogenic/immune-suppressive programs. The synthesized peptide TJ-M11 selectively disrupts TAD interactions with MED15 and TAF4, suppressing tumor growth and sensitizing tumors to immunotherapy. Our findings demonstrate that YAP/TAZ TADs exhibit dual functions in PIC assembly and Pol II elongation via hydrophobic interactions, which represent actionable targets for cancer therapy and combination immunotherapy. |
| WOS关键词 | SWI/SNF COMPLEX ; YAP ; TRANSCRIPTION ; INTEGRATION ; SUPPRESSES ; REVEALS ; PATHWAY ; GROWTH ; BINDS ; TAZ |
| 资助项目 | Ministry of Science and Technology of China[2020YFA0803201] ; National Natural Science Foundation of China[82430095] ; National Natural Science Foundation of China[32270762] ; National Natural Science Foundation of China[82002972] ; Laboratory Animal Center of Huazhong University of Science and Technology |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:001474328800004 |
| 出版者 | NATURE PORTFOLIO |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/317542]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Li, Yan; Sun, Shuguo |
| 作者单位 | 1.Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Oncol, Wuhan, Peoples R China 2.Hubei Key Lab Drug Target Res & Pharmacodynam Eval, Wuhan, Peoples R China 3.Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Basic Med, Dept Human Anat Histol & Embryol, Wuhan, Peoples R China 4.Huazhong Univ Sci & Technol, State Key Lab Diag & Treatment Severe Zoonot Infec, Wuhan, Peoples R China 5.Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Basic Med, Dept Pathogen Biol, Wuhan, Peoples R China 6.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China 7.UCAS, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou, Peoples R China |
| 推荐引用方式 GB/T 7714 | Yu, Man,Wang, Jingning,Zhang, Xiao,et al. The mechanism of YAP/TAZ transactivation and dual targeting for cancer therapy[J]. NATURE COMMUNICATIONS,2025,16(1):20. |
| APA | Yu, Man.,Wang, Jingning.,Zhang, Xiao.,Zhang, Haoran.,Li, Chaoqiang.,...&Sun, Shuguo.(2025).The mechanism of YAP/TAZ transactivation and dual targeting for cancer therapy.NATURE COMMUNICATIONS,16(1),20. |
| MLA | Yu, Man,et al."The mechanism of YAP/TAZ transactivation and dual targeting for cancer therapy".NATURE COMMUNICATIONS 16.1(2025):20. |
入库方式： OAI收割
来源：上海药物研究所
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