Role of CYLD deubiquitinase in myocardial infarction

CYLD is a deubiquitinase that preferentially removes lysine 63-linked polyubiquitin chains from its substrates, thus mainly regulating non-proteolytic cellular functions such as kinase activation, protein trafficking, and signal transduction. CYLD was originally identified as a tumor suppressor and its mutation is responsible for familial cylindromatosis, an autosomal dominant disease characterized by the formation of benign skin tumors. Here we examined the role of CYLD in cardiac homeostasis and pathological remodeling using both global and cardiomyocyte-specific Cyld knockout mouse models. We found that genetic ablation of CYLD did not affect basal cardiac structure and function as assessed by echocardiography. However, genetic inactivation of CYLD attenuated cardiac dysfunction, ventricular dilation, and pathological hypertrophy following myocardial infarction. These data suggest that CYLD deubiquitinase may represent a potential therapeutic target for ischemic heart disease.