CARD9 protein SUMOylation regulates HOXB5 nuclear translocation and Parkin‐mediated mitophagy in myocardial I/R injury

Abstract Myocardial injury induced by ischemia–reperfusion (I/R) remains a difficult clinical problem. However, the exact mechanisms underlying I/R‐induced have yet to be clarified. CARD9 is an important cytoplasmic‐binding protein. In this study, an immunocoprecipitation assay showed that SUMOylation of the CARD9 protein promoted the binding of CARD9 to HOXB5, but hindered the O‐GlcNAc glycosylation of HOXB5, a predicted transcription factor of Parkin and a key factor in mitophagy. O‐GlcNAc glycosylation is an important signal for translocation of proteins from the cytoplasm to the nucleus. CARD9 protein SUMOylation is regulated by PIAS3, which is related to I/R‐induced myocardial injury. Therefore, we propose that knockdown of PIAS3 inhibits SUMOylation of the CARD9 protein, facilitates the dissociation of CARD9 and HOXB5, which increases the O‐GlcNAc‐mediated glycosylation of HOXB5, while the resulting HOXB5 nuclear translocation promotes Parkin‐induced mitophagy and alleviates myocardial I/R injury.