2MJV

Solution structures of second bromodomain of Brd4 with di-acetylated Twist peptide

2MJV の概要

• エントリーDOI: 10.2210/pdb2mjv/pdb
• NMR情報: BMRB: 19738
• 分子名称: Twist-related protein 1, Bromodomain-containing protein 4 (2 entities in total)
• 機能のキーワード: tumorigenesis, transcription
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus: Q15672 O60885
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 16142.52

構造登録者

Zeng, L.,Zhou, M. (登録日: 2014-01-16, 公開日: 2014-03-19, 最終更新日: 2024-11-27)

主引用文献

Shi, J.,Wang, Y.,Zeng, L.,Wu, Y.,Deng, J.,Zhang, Q.,Lin, Y.,Li, J.,Kang, T.,Tao, M.,Rusinova, E.,Zhang, G.,Wang, C.,Zhu, H.,Yao, J.,Zeng, Y.X.,Evers, B.M.,Zhou, M.M.,Zhou, B.P.
Disrupting the Interaction of BRD4 with Diacetylated Twist Suppresses Tumorigenesis in Basal-like Breast Cancer.
Cancer Cell, 25:210-225, 2014

PubMed Abstract: Twist is a key transcription activator of epithelial-mesenchymal transition (EMT). It remains unclear how Twist induces gene expression. Here we report a mechanism by which Twist recruits BRD4 to direct WNT5A expression in basal-like breast cancer (BLBC). Twist contains a "histone H4-mimic" GK-X-GK motif that is diacetylated by Tip60. The diacetylated Twist binds the second bromodomain of BRD4, whose first bromodomain interacts with acetylated H4, thereby constructing an activated Twist/BRD4/P-TEFb/RNA-Pol II complex at the WNT5A promoter and enhancer. Pharmacologic inhibition of the Twist-BRD4 association reduced WNT5A expression and suppressed invasion, cancer stem cell (CSC)-like properties, and tumorigenicity of BLBC cells. Our study indicates that the interaction with BRD4 is critical for the oncogenic function of Twist in BLBC.

PubMed: 24525235
DOI: 10.1016/j.ccr.2014.01.028

実験手法

SOLUTION NMR