8J9A

Solution structure of ABD3 (residues 453-561) of human MED15 isoform 2

8J9A の概要

• エントリーDOI: 10.2210/pdb8j9a/pdb
• NMR情報: BMRB: 36565
• 分子名称: Mediator of RNA polymerase II transcription subunit 15 (1 entity in total)
• 機能のキーワード: mediator of rna polymerase ii transcription subunit 15, transcription
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 13405.51

構造登録者

Zhang, H.,Li, Y. (登録日: 2023-05-03, 公開日: 2024-05-08, 最終更新日: 2025-05-28)

主引用文献

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

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: 40274828
DOI: 10.1038/s41467-025-59309-w

実験手法

SOLUTION NMR