Biomolecular condensates in Hippo pathway regulation

Area of Science:

• Cell Biology
• Molecular Biology
• Cancer Research

Background:

• The Hippo signaling pathway is crucial for cellular processes and development.
• Its dysregulation is linked to cancer development and progression.
• Phase separation into biomolecular condensates is a newly discovered regulatory mechanism.

Purpose of the Study:

• To review recent advances in Hippo signaling regulation by phase separation.
• To focus on transcriptional activation by Yes-associated protein (YAP)/transcriptional coactivator with post-synaptic density-95, disks-large, and zonula occludens-1 (PDZ)-binding domain (TAZ) condensates.
• To discuss therapeutic implications of targeting these condensates.

Main Methods:

• Review of current literature on phase separation and Hippo signaling.
• Analysis of chemical crosslinking combined with mass spectrometry for interactome studies.
• Examination of the role of Fused In Sarcoma (FUS) in TAZ condensate properties.

Main Results:

• Phase separation significantly impacts the spatiotemporal regulation of Hippo signaling.
• TAZ condensates are key mediators of transcriptional activation.
• FUS protein influences TAZ condensate biophysical properties and transcriptional activity.

Conclusions:

• Phase separation offers a novel layer of regulation for Hippo signaling.
• Understanding TAZ condensate dynamics provides insights into cancer progression.
• Targeting YAP/TAZ condensates presents potential therapeutic strategies for related diseases.