Circulation research
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Circulation research · Sep 2012
Human molecular genetic and functional studies identify TRIM63, encoding Muscle RING Finger Protein 1, as a novel gene for human hypertrophic cardiomyopathy.
A delicate balance between protein synthesis and degradation maintains cardiac size and function. TRIM63 encoding Muscle RING Finger 1 (MuRF1) maintains muscle protein homeostasis by tagging the sarcomere proteins with ubiquitin for subsequent degradation by the ubiquitin-proteasome system (UPS). ⋯ TRIM63 mutations, identified in patients with HCM, impart loss-of-function effects on E3 ligase activity and are probably causal mutations in HCM. The findings implicate impaired protein degradation in the pathogenesis of HCM.