Post-Translational Modification of HMGB1 Disulfide Bonds in Stimulating and Inhibiting Inflammation.
Post-Translational Modification of HMGB1 Disulfide Bonds in Stimulating and Inhibiting Inflammation.
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作者：
Andersson U;Tracey KJ;Yang H
高迁移率组框1蛋白（HMGB1）是一种高度保守的核dna结合蛋白，是一种“损伤相关分子模式”分子（DAMP），参与刺激和抑制先天免疫。正如本文所述，HMGB1是一种氧化还原敏感的含有三种半胱氨酸的DAMP，这些残基的翻译后修饰通过结合不同的细胞外细胞表面受体来建立其促炎和抗炎活性。HMGB1的氧化还原敏感信号机制在先天免疫中也占有重要的位置，因为HMGB1可能携带其他DAMPs和病原体相关分子模式分子（PAMPs）。HMGB1与DAMP/PAMP辅因子结合到晚期糖基化终产物（RAGE）的受体上，RAGE通过内吞作用将HMGB1复合物内化，并入溶酶体腔室。溶酶体内HMGB1破坏溶酶体膜，从而释放HMGB1转运的分子，刺激介导炎症的胞质传感器。这种HMGB1-DAMP/PAMP辅助因子途径减缓了诊断或治疗用途的hmgb1结合拮抗剂的发展。然而，最近发现神经元释放的HMGB1通过TLR4受体系统介导炎症，以及癌细胞表达完全氧化的HMGB1作为免疫抑制机制，为靶向HMGB1治疗炎症、疼痛和癌症提供了新的途径。
High mobility group box 1 protein (HMGB1), a highly conserved nuclear DNA-binding protein, is a “damage-associated molecular pattern” molecule (DAMP) implicated in both stimulating and inhibiting innate immunity. As reviewed here, HMGB1 is an oxidation-reduction sensitive DAMP bearing three cysteines, and the post-translational modification of these residues establishes its proinflammatory and anti-inflammatory activities by binding to different extracellular cell surface receptors. The redox-sensitive signaling mechanisms of HMGB1 also occupy an important niche in innate immunity because HMGB1 may carry other DAMPs and pathogen-associated molecular pattern molecules (PAMPs). HMGB1 with DAMP/PAMP cofactors bind to the receptor for advanced glycation end products (RAGE) which internalizes the HMGB1 complexes by endocytosis for incorporation in lysosomal compartments. Intra-lysosomal HMGB1 disrupts lysosomal membranes thereby releasing the HMGB1-transported molecules to stimulate cytosolic sensors that mediate inflammation. This HMGB1-DAMP/PAMP cofactor pathway slowed the development of HMGB1-binding antagonists for diagnostic or therapeutic use. However, recent discoveries that HMGB1 released from neurons mediates inflammation via the TLR4 receptor system, and that cancer cells express fully oxidized HMGB1 as an immunosuppressive mechanism, offer new paths to targeting HMGB1 for inflammation, pain, and cancer.
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影响因子：
4.9
作者：
Abdulahad DA;Westra J;Bijzet J;Limburg PC;Kallenberg CG;Bijl M
通讯作者：
Bijl M
影响因子：
4.6
作者：
Fujita K;Motoki K;Tagawa K;Chen X;Hama H;Nakajima K;Homma H;Tamura T;Watanabe H;Katsuno M;Matsumi C;Kajikawa M;Saito T;Saido T;Sobue G;Miyawaki A;Okazawa H
通讯作者：
Okazawa H
影响因子：
4
作者：
Chen R;Huang Y;Quan J;Liu J;Wang H;Billiar TR;Lotze MT;Zeh HJ;Kang R;Tang D
通讯作者：
Tang D
影响因子：
5.3
作者：
Cai B;Chen F;Ji Y;Kiss L;de Jonge WJ;Conejero-Goldberg C;Szabo C;Deitch EA;Ulloa L
通讯作者：
Ulloa L
DOI：
10.1016/j.bbi.2017.08.018
发表时间：
2018-08
期刊：
Brain, behavior, and immunity
影响因子：
--
作者：
Grace PM;Strand KA;Galer EL;Rice KC;Maier SF;Watkins LR
通讯作者：
Watkins LR