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Sab蛋白的研究进展

Research advances in study of Sab protein
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摘要 Sab(SH3 domain-binding protein that preferentially associates with Btk)蛋白,又称SH3BP5(SH3domain-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p38γ结合,从而调控B细胞抗原受体和线粒体JNK、p38γ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蛋白的表达可改善Btk、JNKs及p38γ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。 Sab (SH3 domain-binding protein that preferentially associates with Btk) that is also called SH3BP5 (SH3 domain-binding protein 5), is a scaffold protein on mitochondrial outer membrane 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 p38γ. Thus Sab can regulate B cell antigen receptor, mitochondrial JNK and p38γ signaling pathway, which is associated with the critical physiological function, such as B-cell development and differentiation and regulation of mitochondrial signaling transcription. Inhibition or induction on the expression of Sab can ameliorate the diseases arising from the abnormal level of Btk, JNKs and p38γ, such as nervous system diseases and liver injury. Therefore, Sab could be expected as a new target for drug development. In this article, we provide an overview of the structure and functions of Sab and its relationship to diseases of diffuse large B-cell lymphoma, nervous system diseases and liver injury, aiming to provide new ideas and theoretical basis for the development of new drugs.
作者 姜剑伟 王蕊 李燕 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)
出处 《药学学报》 CAS CSCD 北大核心 2018年第4期495-499,共5页 Acta Pharmaceutica Sinica
基金 中国医学科学院医学与健康科技创新工程经费资助(2017-I2M-1-010).
关键词 Sab蛋白 结构 功能 靶点 JNK Sab structure function target JNK
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