The Characterization of Taz Protein-Protein Interactions in Myogenic Cells

The Hippo signaling pathway is known to regulate cell proliferation, differentiation, and apoptosis. Recent studies identified the Hippo signaling target protein TAZ as a repressor of myogenic differentiation. Since TAZ lacks inherent DNA binding ability, its activity is dependent on its protein interactions. Using GFP-nanoTrap affinity purification and LC-MS/MS, we documented TAZ protein interactions in muscle cells, including the pro-myogenic methyltransferase CARM1. Investigation of the TAZ and CARM1 interaction revealed that CARM1 represses TAZ transcriptional activation, promoting TAZ Ser89 phosphorylation and cytoplasmic sequestration. The TAZ/CARM1 interaction was further investigated in embryonic rhabdomyosarcoma (RD) cells, where Hippo signaling increased compared to control C2C12 myoblasts. Further, mass spectrometry results suggest that TAZ is a substrate of CARM1 methylation, with methylation at Arg 77 enhancing TAZ Ser89 phosphorylation. These findings highlight the potential role of CARM1 in regulating TAZ function in myogenic cells.