UBE2O-mediated ubiquitylation directs cytoplasmic CTNNA1 to promote cell-to-ECM adhesions.

ABSTRACT: CTNNA1, a multifunctional protein that localizes at both the plasma membrane and the cytosol, plays crucial roles in actin dynamics regulation, cell-to-cell and cell-to-the extracellular matrix (ECM) adhesions and tumor suppression. Despite its diverse functions, the regulatory mechanisms by which cells coordinate CTNNA1's roles remain poorly understood. In this study, we identified UBE2O, a unique hybrid E2/E3 enzyme, as a key regulator that selectively interacts with and ubiquitylates cytosolic CTNNA1 in a phosphorylation-independent manner. Through comprehensive mass spectrometry-based interactome analysis of ubiquitylated CTNNA1, we reveal that the ubiquitylation of CTNNA1 diminishes its interaction with β-catenin while allowing its interaction with vinculin. This switch of molecular i

SUBMITTER: Xiang D 

PROVIDER: S-EPMC12635394 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature