Department of Rehabilitation Medicine, the Affiliated Hospital of Qingdao University, Qingdao, Shandong, P.R. China.
School of Basic Medicine, Qingdao University, Qingdao, Shandong, P.R. China.
Ann Med. 2024 Dec;56(1):2409958. doi: 10.1080/07853890.2024.2409958. Epub 2024 Oct 1.
Apoptosis repressor with caspase recruitment domain (ARC) is a highly potent and multifunctional suppressor of various types of programmed cell death (PCD) (e.g. apoptosis, necroptosis, and pyroptosis) and plays a key role in determining cell fate. Under physiological conditions, ARC is predominantly expressed in terminally differentiated cells, such as cardiomyocytes and skeletal muscle cells. Its expression and activity are tightly controlled by a complicated system consisting of transcription factor (TF), non-coding RNA (ncRNA), and post-translational modification (PTM). ARC dysregulation has been shown to be closely associated with many chronic diseases, including cardiovascular disease, cancer, diabetes, and neurodegenerative disease. However, the detailed mechanisms of ARC involved in the progression of these diseases remain unclear to a large extent. In this review, we mainly focus on the regulatory mechanisms of ARC expression and activity and its role in PCD. We also discuss the underlying mechanisms of ARC in health and disease and highlight the potential implications of ARC in the clinical treatment of patients with chronic diseases. This information may assist in developing ARC-based therapeutic strategies for patients with chronic diseases and expand researchers' understanding of ARC.
凋亡抑制因子含有半胱氨酸蛋白酶募集结构域（ARC），是一种高效且多功能的细胞程序性死亡（PCD）抑制剂，可抑制多种类型的 PCD（如细胞凋亡、坏死性凋亡和细胞焦亡），在决定细胞命运方面发挥关键作用。在生理条件下，ARC 主要在终末分化细胞中表达，如心肌细胞和骨骼肌细胞。其表达和活性受转录因子（TF）、非编码 RNA（ncRNA）和翻译后修饰（PTM）等复杂系统的严格调控。ARC 失调与许多慢性疾病密切相关，包括心血管疾病、癌症、糖尿病和神经退行性疾病。然而，ARC 在这些疾病进展中的详细机制在很大程度上仍不清楚。在这篇综述中，我们主要关注 ARC 表达和活性的调控机制及其在 PCD 中的作用。我们还讨论了 ARC 在健康和疾病中的潜在机制，并强调了 ARC 在慢性疾病患者临床治疗中的潜在意义。这些信息可能有助于为慢性疾病患者开发基于 ARC 的治疗策略，并扩展研究人员对 ARC 的理解。
