The transcriptional co-activator protein TAZ is a major effector of the Hippo pathway, which regulates cell proliferation to control organ size and growth. In myoblasts, nuclear TAZ represses genes involved in myogenesis, whereas its translocation to the cytosol upon activation of Hippo signalling and phosphorylation at serine residue 89 (Ser89) correlates with myogenic differentiation. TAZ does not directly interact with Hippo-responsive genes but relies on intermediate interactions with a range of other proteins. As these interactors can be context and cell type dependent, a better understanding of the TAZ interactome is needed. In this Tools and Resources article (Kelebeev et al., 2025), John McDermott and colleagues describe an unbiased screen for TAZ interactors in C2C12 myoblasts and neonatal rat cardiomyocytes. This flexible protocol uses purified ‘bait’ protein bound to nanobody-coated beads to extract interactors from cell lysates, overcoming the need for ectopic bait expression in difficult-to-transfect cells like myocytes. The authors identify, in addition to Hippo pathway factors and DNA-binding proteins, the methyltransferase CARM1 as a novel TAZ interactor. They validate this by showing that CARM1 counteracts repression of myogenic transcription by methylating TAZ, which likely promotes Ser89 phosphorylation and cytosolic translocation. Overall, this study provides a robust and generally applicable method for identifying protein interactomes and shares novel data on the TAZ interactome in striated muscle cells.
