A Role for LDB3 Acetylation in the Heart: Does LDB3 Acetylation Promote Cardiomyocyte Hypertrophy
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Heart failure is a public health concern, with a 5-year mortality rate of approximately 50%. Hallmarks of this disease include structural changes to the heart that entail cardiac enlargement and fibrosis as well as dysfunction of the contractile units within the sarcomere. LIM Domain Binding 3 (LDB3) protein, the human ortholog of Cypher, is a scaffolding protein located in the Z-disc of the sarcomere. Its fundamental role is to assist in the contraction of muscles, both in heart and skeletal muscle. Mutations in LDB3 results in cardiomyopathy and failure of the heart. These mutations are thought to disrupt sarcomere integrity and function. In addition, LDB3 binds to Calcineurin (CaN), a protein which is directly involved in the regulation of Nuclear Factor of Activated T-cells (NFAT) signaling, which leads to pathological hypertrophic gene expression. We found that LDB3 was acetylated in obese hearts of mice. We therefore tested the postulate that acetylated LDB3 (Ac-LDB3) regulates CaN/NFAT signaling to promote pathological cardiac myocytes.