摘要Tax1 banding protein 1(Tax1bp1)was originally identified as an NF-KB regulatory protein that participated in inflammatory,antiviral and Innate immune processes.Tax1 bp1 also functions as an autophagy receptor that plays a role in autophagy.Our previous study shows that Tax1 bp1 protects against cardiomyopathy in STZ-induced diabetic mice.In this study we investigated the role of Tax1bp1 in heart failure.Pressure overload-induced heart failure model was established in mice by aortic banding(AB)surgery,and angiotensin Ⅱ(Ang Ⅱ)-induced heart failure model was established by infusion of Ang Ⅱ through osmotic minipump for 4 weeks.We showed that the expression levels of Tax1bp1 in the heart were markedly increased 2 and 4 weeks after AB surgery.Knockdown of Tax1bp1 in mouse hearts significantly ameliorated both AB-and Ang Ⅱ infusion-induced heart failure parameters.On the contrary,AB-induced heart failure was aggravated in cardiac-specific Tax1bp1 transgenic mice.Similar results were observed in neonatal rat cardiomyocytes(NRCMs)under Ang Ⅱ insult.We demonstrated that the pro-heart failure effect of Tax1bp1 resulted from its interaction with the E3 ligase ITCH to promote the transcription factor P73 ubiquitination and degradation,causing enhanced BCL2 interacting protein 3(BNIP3)-mediated cardiomyocyte apoptosis.Knockdown ITCH or BNIP3 in NRCMs significantly reduced Ang Ⅱ-induced apoptosis in vitro.Similarly,BNIP3 knockdown attenuated heart failure in cardiac-specific Tax1bp1 transgenic mice.In the left ventricles of heart failure patients,Tax1 bp1 expression level was significantly increased;Tax1 bp1 gene expression was negatively correlated with left ventricular ejection fraction in heart failure patients.Collectively,the Tax1 bp1 increase in heart failure enhances ITCH-P73-BNIP3-mediated cardiomyocyte apoptosis and induced cardiac injury.Tax1 bp1 may serve as a potent therapeutic target for the treatment of heart failure.