Abstract：
High mobility group protein B1 (HMGB1) acts as a pathogenic inflammatory response to mediate ranges of conditions such as epilepsy, septic shock, ischemia, traumatic brain injury, Parkinson\'s disease, Alzheimer\'s disease and mass spectrometry. HMGB1 promotes inflammation during sterile and infectious damage and plays a crucial role in disease development. Mobilization from the nucleus to the cytoplasm is the first important step in the release of HMGB1 from activated immune cells. Here, we demonstrated that Sirtuin 2 (SIRT2) physically interacts with and deacetylates HMGB1 at 43 lysine residue at nuclear localization signal locations, strengthening its interaction with HMGB1 and causing HMGB1 to be localized in the cytoplasm. These discoveries are the first to shed light on the SIRT2 nucleoplasmic shuttle, which influences HMGB1 and its degradation, hence revealing novel therapeutic targets and avenues for neuroinflammation treatment.
摘要：
高迁移率族蛋白B1（HMGB1）作为致病性炎症反应，介导各种疾病，如癫痫，感染性休克,缺血,创伤性脑损伤,帕金森病,阿尔茨海默病和质谱。HMGB1在无菌和感染性损伤期间促进炎症，并在疾病发展中起关键作用。从细胞核动员到细胞质是活化免疫细胞释放HMGB1的第一步重要步骤。这里,我们证明了Sirtuin2（SIRT2）在43个赖氨酸残基的核定位信号位置与HMGB1物理相互作用并去乙酰化，加强其与HMGB1的相互作用并使HMGB1定位于细胞质中。这些发现是第一个揭示SIRT2核质穿梭的发现，影响HMGB1及其降解，因此揭示了神经炎症治疗的新治疗靶点和途径。
