6IUR

A phosphatase complex STRN3-PP2Aa

6IUR の概要

• エントリーDOI: 10.2210/pdb6iur/pdb
• 分子名称: PP2A scaffolding subunit, Striatin-3, PROPANE, ... (4 entities in total)
• 機能のキーワード: phosphatase, complex, protein binding
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 285389.42

構造登録者

Tang, Y.,Zhou, Z.C. (登録日: 2018-11-30, 公開日: 2019-12-04, 最終更新日: 2023-11-22)

主引用文献

Tang, Y.,Fang, G.,Guo, F.,Zhang, H.,Chen, X.,An, L.,Chen, M.,Zhou, L.,Wang, W.,Ye, T.,Zhou, L.,Nie, P.,Yu, H.,Lin, M.,Zhao, Y.,Lin, X.,Yuan, Z.,Jiao, S.,Zhou, Z.
Selective Inhibition of STRN3-Containing PP2A Phosphatase Restores Hippo Tumor-Suppressor Activity in Gastric Cancer.
Cancer Cell, 38:115-128.e9, 2020

PubMed Abstract: Loss of Hippo tumor-suppressor activity and hyperactivation of YAP are commonly observed in cancers. Inactivating mutations of Hippo kinases MST1/2 are uncommon, and it remains unclear how their activity is turned off during tumorigenesis. We identified STRN3 as an essential regulatory subunit of protein phosphatase 2A (PP2A) that recruits MST1/2 and promotes its dephosphorylation, which results in YAP activation. We also identified STRN3 upregulation in gastric cancer correlated with YAP activation and poor prognosis. Based on this mechanistic understanding and aided by structure-guided medicinal chemistry, we developed a highly selective peptide inhibitor, STRN3-derived Hippo-activating peptide, or SHAP, which disrupts the STRN3-PP2Aa interaction and reactivates the Hippo tumor suppressor, inhibits YAP activation, and has antitumor effects in vivo.

PubMed: 32589942
DOI: 10.1016/j.ccell.2020.05.019

実験手法

X-RAY DIFFRACTION (3.33 Å)