8J9A
Solution structure of ABD3 (residues 453-561) of human MED15 isoform 2
Summary for 8J9A
| Entry DOI | 10.2210/pdb8j9a/pdb |
| NMR Information | BMRB: 36565 |
| Descriptor | Mediator of RNA polymerase II transcription subunit 15 (1 entity in total) |
| Functional Keywords | mediator of rna polymerase ii transcription subunit 15, transcription |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 13405.51 |
| Authors | |
| Primary citation | Yu, M.,Wang, J.,Zhang, X.,Zhang, H.,Li, C.,Li, J.,Lin, J.,Zheng, J.,Huang, L.,Li, Y.,Sun, S. The mechanism of YAP/TAZ transactivation and dual targeting for cancer therapy. Nat Commun, 16:3855-3855, 2025 Cited by 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. PubMed: 40274828DOI: 10.1038/s41467-025-59309-w PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
Download full validation report
