{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["16(1)"],"submitter":["Yu M"],"pubmed_abstract":["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."],"journal":["Nature communications"],"pagination":["3855"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12022045"],"repository":["biostudies-literature"],"pubmed_title":["The mechanism of YAP/TAZ transactivation and dual targeting for cancer therapy."],"pmcid":["PMC12022045"],"pubmed_authors":["Zheng J","Li Y","Yu M","Li J","Li C","Zhang X","Zhang H","Sun S","Lin J","Huang L","Wang J"],"additional_accession":[]},"is_claimable":false,"name":"The mechanism of YAP/TAZ transactivation and dual targeting for cancer therapy.","description":"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.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Apr","modification":"2026-06-02T10:14:27.097Z","creation":"2025-07-01T03:05:40.36Z"},"accession":"S-EPMC12022045","cross_references":{"pubmed":["40274828"],"doi":["10.1038/s41467-025-59309-w"]}}