Huang Xianwei, Liu Yixuan, Liu Xiong, Liu Ping, Lin Jiyan
Department of Cardiology, The Second Hospital of Shandong University, Jinan, Shandong, China.
Emergency Department, The First Affiliated Hospital of Xiamen University, Xiamen Key Laboratory for Clinical Efficacy and Evidence-Based Research of Traditional Chinese Medicine, Xiamen, China.
IUBMB Life. 2025 Mar;77(3):e70012. doi: 10.1002/iub.70012.
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.
巨噬细胞内脂质过度积累引发的泡沫细胞形成是动脉粥样硬化发展的一个标志。清道夫受体-A（SR-A）是氧化型低密度脂蛋白（oxLDL）诱导泡沫细胞形成过程中巨噬细胞摄取脂质的关键调节因子。泛素化是一种关键的翻译后修饰，可调节靶蛋白的稳定性和功能，但SR-A是否被泛素化以及泛素化如何影响SR-A功能尚不清楚。我们发现，卵巢肿瘤结构域蛋白酶1（OTUB1）是一种去除靶蛋白泛素化的去泛素酶（DUBs），可在293T细胞和THP-1巨噬细胞中稳定SR-A。敲低THP-1巨噬细胞中的OTUB1可降低SR-A蛋白水平，并损害oxLDL处理的THP-1巨噬细胞中的脂质积累，过量的SR-A可挽救这种情况。这些数据表明，OTUB1介导的SR-A稳定可能对泡沫细胞形成过程中巨噬细胞的脂质积累至关重要。
