TGF-β-induced DACT1 biomolecular condensates repress Wnt signalling to promote bone metastasis.

ABSTRACT: The complexity of intracellular signalling requires both a diversity of molecular players and the sequestration of activity to unique compartments within the cell. Recent findings on the role of liquid-liquid phase separation provide a distinct mechanism for the spatial segregation of proteins to regulate signalling pathway crosstalk. Here, we discover that DACT1 is induced by TGFβ and forms protein condensates in the cytoplasm to repress Wnt signalling. These condensates do not localize to any known organelles but, rather, exist as phase-separated proteinaceous cytoplasmic bodies. The deletion of intrinsically disordered domains within the DACT1 protein eliminates its ability to both form protein condensates and suppress Wnt signalling. Isolation and mass spectrometry analysis of these pa

SUBMITTER: Esposito M 

PROVIDER: S-EPMC7970447 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature