Investigating the functional components of YAP condensates

Area of Science:

• Cell biology
• Molecular biology
• Biochemistry

Background:

• Yes-associated protein (YAP) condensates play a vital role in cellular responses to hyperosmotic stress.
• The precise mechanisms by which YAP condensates function remain largely unknown.

Purpose of the Study:

• To identify proteins that interact with YAP in both diffuse and condensate states.
• To elucidate the functional roles of YAP-interacting proteins in hyperosmotic stress response.

Main Methods:

• Proximity-based proteomics was utilized to identify YAP-interacting proteins.
• Immunofluorescence microscopy was employed to visualize protein localization within YAP condensates.
• Depletion studies were conducted to assess the necessity of identified proteins for condensate formation and function.

Main Results:

• YAP condensate formation significantly altered the composition of interacting proteins.
• YAP condensates transitioned from chromatin clustering to transcriptional activation.
• JUNB, TCF12, and IFI16 were identified as enriched components of YAP condensates.
• Depletion of JUNB and TCF12 inhibited YAP condensate assembly and downstream gene expression.

Conclusions:

• Novel protein components, including JUNB and TCF12, are essential for YAP condensate formation and function.
• These findings reveal the dynamic roles of YAP condensates in the hyperosmotic stress response.
• The study provides a basis for developing therapeutic strategies targeting YAP condensates.