Investigating the functional components of YAP condensates

Yes-associated protein (YAP) condensates are critical for cell survival under hyperosmotic stress, yet how these condensates execute their specific functions remains incompletely understood. Here, we employed proximity-based proteomics to identify YAP-interacting proteins in both the diffuse and condensate-forming states. Upon YAP condensate formation, the composition of YAP-interacting proteins changed markedly. Moreover, YAP condensate components transitioned from an initial chromatin-clustering state to a subsequent transcriptional activation state. Using immunofluorescence, we verified that JUNB, TCF12, and IFI16 were enriched within endogenous YAP condensates. Notably, JUNB and TCF12 are also required for YAP condensate formation and function, as their depletion completely abolished condensate assembly and downstream gene expression. Together, these findings identify novel components essential for YAP condensate formation and illuminate their roles in the hyperosmotic stress response, providing a foundation for future therapeutic strategies targeting YAP condensates.