Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng 475004, China; School of Stomatology, Henan University, Kaifeng 475004, China.
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng 475004, China.
Int Immunopharmacol. 2024 Dec 25;143(Pt 1):113369. doi: 10.1016/j.intimp.2024.113369. Epub 2024 Oct 14.
As BAG family members, Bcl-2 associated athanogene family protein 1 (BAG1) and 2 (BAG2) are implicated in multiple cellular processes, including apoptosis, autophagy, protein folding and homeostasis. Although structurally similar, they considerably differ in many ways. Unlike BAG2, BAG1 has four isoforms (BAG1L, BAG1M, BAG1S and BAG1 p29) displaying different expression features and functional patterns. BAG1 and BAG2 play different cellular functions by interacting with different molecules to participate in the regulation of various diseases, including cancer/tumor and neurodegenerative diseases. Commonly, BAG1 acts as a protective factor to predict a good prognosis of patients with some types of cancer or a risk factor in some other cancers, while BAG2 is regarded as a risk factor to promote cancer/tumor progression. In neurodegenerative diseases, BAG2 commonly acts as a neuroprotective factor. In this review, we summarized the differences in molacular structure and biological function between BAG1 and BAG2, as well as the influences of them on pathogenesis of diseases, and explore the prospects for their clinical therapy application by specifying the activators and inhibitors of BAG1 and BAG2, which might provide a better understanding of the underlying pathogenesis and developing the targeted therapy strategies for diseases.
作为 BAG 家族成员，Bcl-2 相关抗凋亡基因家族蛋白 1（BAG1）和 2（BAG2）参与多种细胞过程，包括细胞凋亡、自噬、蛋白质折叠和内稳态。尽管结构相似，但它们在许多方面存在显著差异。与 BAG2 不同，BAG1 有四个亚型（BAG1L、BAG1M、BAG1S 和 BAG1 p29），表现出不同的表达特征和功能模式。BAG1 和 BAG2 通过与不同的分子相互作用发挥不同的细胞功能，参与多种疾病的调节，包括癌症/肿瘤和神经退行性疾病。通常情况下，BAG1 作为一种保护因素，预测某些类型癌症患者的预后良好，而在其他一些癌症中则是一种风险因素，而 BAG2 被认为是促进癌症/肿瘤进展的风险因素。在神经退行性疾病中，BAG2 通常作为一种神经保护因子发挥作用。在本文中，我们总结了 BAG1 和 BAG2 在分子结构和生物学功能上的差异，以及它们对疾病发病机制的影响，并通过明确 BAG1 和 BAG2 的激活剂和抑制剂，探讨了它们在临床治疗应用中的前景，这可能为更好地理解潜在发病机制和开发疾病的靶向治疗策略提供帮助。
