Sab蛋白的研究进展ResearchadvancesofSab.PDFVIP

Sab 白的研究进展 姜剑伟，王蕊，李燕*1 （中国医学科学院、北京协和医学院药物研究所，创新药物非临床药物代谢及PK/PD 研究 北京市重点实验室，北京 100050） 摘要：Sab （SH3 domain-binding protein that preferentially associates with Btk）蛋白，又 称SH3BP5 （SH3 domain-binding protein 5）蛋白，是具有调控线粒体生理功能的线粒体外膜 支架蛋白，可与酪氨酸激酶Btk (Bruton s tyrosine kinase)、丝氨酸-苏氨酸激酶JNKs (c-Jun amino-terminal kinases) 及p38 结合，从而调控B 细胞抗原受体和线粒体JNK 、p38 信号通 路，参与B 细胞生长发育和线粒体信号转录等重要生理过程。调节 Sab 蛋白的表 可改善 Btk 、JNKs 及p38 异常引起的相关疾病，如神经系统疾病和肝损伤等，因而Sab 蛋白有望 成为药物研发的潜在靶点。本文简述了 Sab 蛋白的结构、功能及与弥漫大B 细胞淋巴瘤、 神经系统疾病和急性肝损伤的关系，旨在为药物研发提供新的思路和理论依据。 关键词：Sab 蛋白；结构；功能；靶点；JNK 中图分类号: R966 文献标识码: A 文章编号: 0513-4870(2017)0 Research advances of Sab * JIANG Jian-wei, WANG Rui, LI Yan (Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China) Abstract: Sab (SH3 domain-binding protein that preferentially associates with Btk), also called SH3BP5 (SH3 domain-binding protein 5), is a scaffold protein on mitochondrial outer membrane which is involved in the modulation of mitochondrial function. Sab not only combines with the tyrosine kinase Btk (Bruton s tyrosine kinase), but also binds to the serine threonine kinase JNKs (c-Jun amino-terminal kinases) and p38 . Thus Sab can regulate B cell 收稿日期: 2017-10-25; 修回日期: 2017-11-14. 基金项目: 中国医学科学院医学与健康科技创新工程经费资助 (2017-I2M-1-0 10). *通讯作者Tel: 86-10 E-mail: yanli@imm.ac.cn DOI: 10.16438/j.0513-4870.2017-1054 antigen receptor, mitochondrial JNK and p38 signaling pathway, which is associated with the critical physiological function, such as B-cell development and differentiation and regulation of mitochondrial s