Chemerin-stimulated HSP90AB1 SUMOylation promotes monocyte activation and ERK1/2 phosphorylation via β2 integrin

Post-translational modification through SUMOylation plays a critical role in the pathogenesis of cardiovascular diseases, including atherosclerosis, by modulating the interactions of target proteins and their cellular functionality. Our previous results indicated that chemerin stimulated monocyte adhesion by activating β2 integrin via its protein disulfide isomerase (PDI)-like activity. However, the downstream mechanism remains unclear. In this study, we observed a global increase in the SUMO2/3 conjugation of proteins in monocytes induced by chemerin via its receptor β2 integrin. To investigate the functional significance of SUMO2/3 in cellular activities, we examined the effects of the SUMOylation inhibitor ML-792 and observed that it effectively reversed chemerin-induced monocyte activation and adhesion. Moreover, our results demonstrated that chemerin enhances ERK1/2 phosphorylation in a SUMOylation-dependent manner in monocytes. Immunoprecipitation (IP) and liquid chromatography–tandem mass spectrometry (LC–MS/MS) analysis revealed a direct interaction between HSP90AB1 and SUMO2/3, which is essential for chemerin-induced protein SUMOylation and subsequent ERK1/2 phosphorylation. These findings suggest that chemerin-induced protein SUMOylation via β2 integrin in monocytes promotes ERK1/2 phosphorylation and monocyte activation and adhesion, providing new insights into the molecular mechanisms underlying atherosclerosis and identifying potential therapeutic targets for its treatment.