Abstract P1010: Acetylation Regulates Yap Subcellular Localization In Heart Regeneration

The core Hippo pathway effector YAP is a transcription co-factor that directs the expression of genes that promote cardiomyocyte renewal. The Hippo kinases phosphorylate YAP and prevent its nuclear localization, underscoring the importance of post-translational modifications on YAP-mediated transcription. Here, we discovered a lysine acetylation-deacetylation cycle-regulated YAP acetylation in cardiomyocytes. acetylated-YAP is prone to cytoplasmic localization and showed reduced YAP activity compared with WT YAP. In addition, mice that harbor the mutation with abolished YAP acetylation showed better heart regeneration than the controls after myocardial infarction. Thus, our study revealed a novel mechanism that acetylation suppresses YAP activity in cardiomyocytes. Given that there are many clinic-approved compounds targeting acetylation enzymes, we believe our study would guide the development of new strategies targeting YAP acetylation for ischemic heart diseases.