The Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Department of Medicine, Division of Cardiology, The Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
Int J Mol Sci. 2024 Oct 21;25(20):11308. doi: 10.3390/ijms252011308.
Bcl-2-associated athanogene 3 (BAG3) plays an important function in cellular protein quality control (PQC) maintaining proteome stability. Mutations in the gene result in cardiomyopathies. Due to its roles in cardiomyopathies and the complexity of BAG3-protein interactions, it is important to understand these protein interactions given the importance of the multifunctional cochaperone BAG3 in cardiomyocytes, using an in vitro cardiomyocyte model. The experimental assay was conducted using high pressure liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) in the human AC16 cardiomyocyte cell line with BioID technology. Proteins with BAG3-interaction were identified in all the 28 hallmark gene sets enriched in idiopathic cardiomyopathies and/or ischemic disease. Among the 24 hallmark gene sets enriched in both idiopathic cardiomyopathies and ischemic disease, 15 gene sets had at least 3 proteins with BAG3-interaction. This study highlights BAG3 protein interactions, unveiling the key gene sets affected in cardiomyopathies, which help to explain the molecular mechanisms of the cardioprotective effects of BAG3. In addition, this study also highlighted the complexity of proteins with BAG3 interactions, implying unwanted effects of BAG3.
Bcl-2 相关抗凋亡基因 3（BAG3）在细胞蛋白质量控制（PQC）中发挥重要作用，维持蛋白质组稳定性。该基因的突变可导致心肌病。鉴于多功能共伴侣 BAG3 在心肌细胞中的重要作用，以及 BAG3 蛋白相互作用的复杂性，了解这些蛋白相互作用非常重要。本研究使用高压液相色谱-串联质谱（LC-MS/MS）结合 BioID 技术在人类 AC16 心肌细胞系中进行了实验检测。在所有富含特发性心肌病和/或缺血性疾病的 28 个标志性基因集中鉴定出与 BAG3 相互作用的蛋白。在富含特发性心肌病和缺血性疾病的 24 个标志性基因集中，有 15 个基因集至少有 3 个与 BAG3 相互作用的蛋白。本研究强调了 BAG3 蛋白相互作用，揭示了心肌病中受影响的关键基因集，有助于解释 BAG3 的心脏保护作用的分子机制。此外，本研究还强调了与 BAG3 相互作用的蛋白质的复杂性，暗示 BAG3 可能存在不良反应。
