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

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.