6IUR

A phosphatase complex STRN3-PP2Aa

Summary for 6IUR

• Entry DOI: 10.2210/pdb6iur/pdb
• Descriptor: PP2A scaffolding subunit, Striatin-3, PROPANE, ... (4 entities in total)
• Functional Keywords: phosphatase, complex, protein binding
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 8
• Total formula weight: 285389.42

Authors

Tang, Y.,Zhou, Z.C. (deposition date: 2018-11-30, release date: 2019-12-04, Last modification date: 2023-11-22)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (3.33 Å)