OTUB1 facilitates lipid accumulation in oxLDL‐induced THP‐1 macrophages by stabilizing scavenger receptor‐A

Abstract The formation of foam cells triggered by excessive lipid accumulation within macrophages is a hallmark of atherosclerosis development. Scavenger receptor‐A (SR‐A) is a key regulator of lipid uptake by macrophages during oxidized low‐density lipoprotein (oxLDL)‐induced foam cell formation. Ubiquitination is a crucial post‐translational modification that regulates the stability and function of targeted proteins, but whether SR‐A is ubiquitinated and how ubiquitination affects SR‐A function is unknown. We found that ovarian tumor domain protease 1 (OTUB1), a deubiquitinase (DUBs) that removes ubiquitination of targeted proteins, can stabilize SR‐A in 293 T cells and THP‐1 macrophages. Knockdown of OTUB1 in THP‐1 macrophages reduced the SR‐A protein level and impaired lipid accumulation in oxLDL‐treated THP‐1 macrophages, which can be rescued by excessive SR‐A. These data suggested that OTUB1‐mediated stabilization of SR‐A may be critical for lipid accumulation in macrophages during foam cell formation.