p55γ degrades RIP3 via MG53 to suppress ischemia-induced myocardial necroptosis and mediates cardioprotection of preconditioning.

Cardiomyocyte death is an essential process in the pathophysiology of myocardial ischemia reperfusion injury and targeting the mechanism of cell death is considered to be a promising cardioprotective therapy. p55γ is a primary determinant of cardiac ischemic preconditioning. Ischemic preconditioning increases p55γ expression and suppresses necroptosis and apoptosis, thus preventing the lethal reperfusion injury. p55γ directly binds and down-regulates RIP3 through interaction with MG53 E3 ligase. We demonstrated that targeted activation of p55γ holds potential therapeutic value for treating ischemic heart disease.