HMGB1 in health and disease.
HMGB1 in health and disease.
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DOI：
10.1016/j.mam.2014.05.001
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发表时间：
2014-12
影响因子：
10.6
通讯作者：
Tang, Daolin
中科院分区：
文献类型：
--
作者：
Kang, Rui;Chen, Ruochan;Zhang, Qiuhong;Hou, Wen;Wu, Sha;Cao, Lizhi;Huang, Jin;Yu, Yan;Fan, Xue-gong;Yan, Zhengwen;Sun, Xiaofang;Wang, Haichao;Wang, Qingde;Tsung, Allan;Billiar, Timothy R.;Zeh, Herbert J., III;Lotze, Michael T.;Tang, Daolin
复杂的遗传和生理变异以及环境因素导致染色体不稳定、细胞非程序性死亡、不对称分化和代谢改变，是人类疾病和障碍发病的核心。了解这些过程的分子基础对于开发新的诊断生物标记物和确定新的治疗靶点非常重要。1973年，一组具有高电泳率的非组蛋白核蛋白被发现，并被称为高迁移率组(High-Mobility Group，HMG)蛋白。HMG蛋白包括HMGB、HMGN和HMGA三个超家族。高迁移率族蛋白1(HMGB1)是含量最丰富、研究最深入的HMG蛋白，它能够感知和协调细胞内的应激反应，不仅在细胞内作为DNA伴侣、染色体守护者、自噬的维持者和细胞死亡的保护者发挥重要作用，而且在细胞外也作为典型的损伤相关分子模式分子(DAMP)发挥重要作用。因此，这种潮湿与其他因素一起，具有细胞因子、趋化因子和生长因子的活性，协调炎症和免疫反应。所有这些特性使HMGB1成为多种人类疾病的关键分子靶点，包括传染病、缺血、免疫紊乱、神经退行性疾病、代谢紊乱和癌症。事实上，一些紧急策略已经被用来在体外和体内抑制HMGB1的表达、释放和活性。这些包括抗体、多肽抑制物、RNAi、抗凝剂、内源性激素、各种化合物、HMGB1受体和信号通路抑制、人工DNA、包括迷走神经刺激在内的物理策略和其他外科方法。未来进一步研究HMGB1的定位、结构、翻译后修饰以及确定其他合作伙伴的细节，无疑将揭开关于HMGB1的S多功能的更多秘密。
Complex genetic and physiological variations as well as environmental factors that drive emergence of chromosomal instability, development of unscheduled cell death, skewed differentiation, and altered metabolism are central to the pathogenesis of human diseases and disorders. Understanding the molecular bases for these processes is important for the development of new diagnostic biomarkers, and for identifying new therapeutic targets. In 1973, a group of non-histone nuclear proteins with high electrophoretic mobility was discovered and termed High-Mobility Group (HMG) proteins. The HMG proteins include three superfamilies termed HMGB, HMGN, and HMGA. High-mobility group box 1 (HMGB1), the most abundant and well-studied HMG protein, senses and coordinates the cellular stress response and plays a critical role not only inside of the cell as a DNA chaperone, chromosome guardian, autophagy sustainer, and protector from apoptotic cell death, but also outside the cell as the prototypic damage associated molecular pattern molecule (DAMP). This DAMP, in conjunction with other factors, thus has cytokine, chemokine, and growth factor activity, orchestrating the inflammatory and immune response. All of these characteristics make HMGB1 a critical molecular target in multiple human diseases including infectious diseases, ischemia, immune disorders, neurodegenerative diseases, metabolic disorders, and cancer. Indeed, a number of emergent strategies have been used to inhibit HMGB1 expression, release, and activity in vitro and in vivo. These include antibodies, peptide inhbitiors, RNAi, anti-coagulants, endogenous hormones, various chemical compounds, HMGB1-receptor and signaling pathway inhibition, artificial DNAs, physical strategies including vagus nerve stimulation and other surgical approaches. Future work further investigating the details of HMGB1 localizationtion, structure, post-translational modification, and identifccation of additional partners will undoubtedly uncover additional secrets regarding HMGB1’s multiple functions.
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影响因子：
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作者：
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