F-box Protein FBXL16 Binds PP2A-B55 and Regulates Differentiation of Embryonic Stem

The programmed formation of specific tissues from em-bryonic stem cells is a major goal of regenerative medi-cine. To identify points of intervention in cardiac tissue formation, we performed an siRNA screen in murine em-bryonic stem cells to identify ubiquitin system genes that repress cardiovascular tissue formation. Our screen un-covered an F-box protein, Fbxl16, as a repressor of one of the earliest steps in the cardiogenic lineage: FLK1 pro-genitor formation. Whereas F-box proteins typically form SCF ubiquitin ligases, shotgun mass spectrometry re-vealed that FBXL16 instead binds protein phosphatase 2A (PP2A) containing a B55 specificity subunit (PP2AB55). Phosphoproteomic analyses indicate that FBXL16 nega-tively regulates phosphorylation of the established PP2AB55 substrate, vimentin. We suggest that FBXL16 negatively regulates the activity of B55-PP2A to modu-late the genesis of FLK1 progenitor cells. Molecular &amp