Chen Ruochan, Kang Rui, Tang Daolin
Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
Exp Mol Med. 2022 Feb;54(2):91-102. doi: 10.1038/s12276-022-00736-w. Epub 2022 Feb 25.
High mobility group box 1 (HMGB1) is a nonhistone nuclear protein that has multiple functions according to its subcellular location. In the nucleus, HMGB1 is a DNA chaperone that maintains the structure and function of chromosomes. In the cytoplasm, HMGB1 can promote autophagy by binding to BECN1 protein. After its active secretion or passive release, extracellular HMGB1 usually acts as a damage-associated molecular pattern (DAMP) molecule, regulating inflammation and immune responses through different receptors or direct uptake. The secretion and release of HMGB1 is fine-tuned by a variety of factors, including its posttranslational modification (e.g., acetylation, ADP-ribosylation, phosphorylation, and methylation) and the molecular machinery of cell death (e.g., apoptosis, pyroptosis, necroptosis, alkaliptosis, and ferroptosis). In this minireview, we introduce the basic structure and function of HMGB1 and focus on the regulatory mechanism of HMGB1 secretion and release. Understanding these topics may help us develop new HMGB1-targeted drugs for various conditions, especially inflammatory diseases and tissue damage.
高迁移率族蛋白B1（HMGB1）是一种非组蛋白核蛋白，根据其亚细胞定位具有多种功能。在细胞核中，HMGB1是一种DNA伴侣蛋白，维持染色体的结构和功能。在细胞质中，HMGB1可通过与BECN1蛋白结合促进自噬。在其主动分泌或被动释放后，细胞外HMGB1通常作为一种损伤相关分子模式（DAMP）分子，通过不同受体或直接摄取来调节炎症和免疫反应。HMGB1的分泌和释放受到多种因素的精细调节，包括其翻译后修饰（如乙酰化、ADP-核糖基化、磷酸化和甲基化）以及细胞死亡的分子机制（如凋亡、焦亡、坏死性凋亡、碱中毒和铁死亡）。在本综述中，我们介绍了HMGB1的基本结构和功能，并重点关注HMGB1分泌和释放的调节机制。了解这些主题可能有助于我们开发针对各种病症的新型HMGB1靶向药物，尤其是炎症性疾病和组织损伤。
