组氨酸三聚体核苷结合蛋白1和2与疾病相关的研究进展  

Research Progress of Histidine Triad Nucleotide-Binding Protein 1 and 2 in Relation to Diseases

作　　者：马赛男 李铁松[1] MA Sainan;LI Tiesong(College of Life Sciences,Lamprey Research Center,Key Laboratory of Liaoning Provincial Biotechnology and Drug Discovery,Liaoning Normal University,Dalian 116081,China)

机构地区：[1]辽宁师范大学生命科学学院七鳃鳗研究中心,生物技术与分子药物研发省重点实验室,大连116081

出　　处：《中国细胞生物学学报》2021年第3期626-633,共8页Chinese Journal of Cell Biology

基　　金：国家自然科学基金青年基金(批准号:31501907);辽宁省教育厅科学技术基金(批准号:L2015287)资助的课题。

摘　　要：组氨酸三聚体核苷结合蛋白(HINT)属于HIT蛋白超家族,HINT1和HINT2基因分别位于人类染色体5q31.2和9p11区域,编码产物分别是含126和163个氨基酸的蛋白,相对分子质量分别约14 kDa和17 kDa,二者之间有61%的序列同源性。HINT1在细胞中定位于细胞质和细胞核,HINT2定位于线粒体,二者在组织中分布广泛。HINT1和HINT2两个亚型均为肿瘤抑制因子,参与细胞增殖和凋亡,HINT1可通过调节Wnt/β-catenin信号通路以及p27^(KIP1)、AP1、TFIIH、MITF等转录因子的活性抑制肿瘤,HINT2可通过线粒体自噬和线粒体凋亡途径抑制肿瘤。该文就HINT1和HINT2的发现、分布、结构、酶活性、肿瘤作用机制及其与其他疾病的关系进行了系统综述并进行展望。为进一步揭示HINT1和HINT2在不同类型肿瘤中的分子抑制机制以及靶向治疗和药物研发奠定了理论基础。HINT(histidine triad nucleoside-binding protein)belongs to the HIT protein superfamily.HINT1 and HINT2 genes are located in the 5q31.2 and 9p11 regions of human chromosome,respectively.The encoded products are proteins containing 126 and 163 amino acids,respectively.Their relative molecular masses are about 14 kDa and 17 kDa,respectively,and there is 61%sequence homology between HINT1 and HINT2.HINT1 is located in the cytoplasm and nucleus,and HINT2 is located in the mitochondria,both of which are widely distributed in tissues.The subtypes of HINT1 and HINT2 are tumor suppressor factors,which are involved in cell proliferation and apoptosis.HINT1 can suppress tumors by regulating Wnt/β-catenin signaling pathway,the activity of p27^(KIP1),AP1,TFIIH,MITF and other transcription factors.HINT2 can suppress tumors by mitochondrial autophagy and mitochondrial pathways of apoptosis.This article reviews the discovery,distribution,structure,enzyme activity,tumor mechanism and other related disease of HINT1 and HINT2.It lays a theoretical foundation for further revealing the molecular inhibitory mechanism of HINT1 and HINT2 in different types of tumors,as well as targeted therapy and drug development.

关 键 词：组氨酸三聚体核苷结合蛋白 HINT1 HINT2 肿瘤 增殖和凋亡 

分 类 号：R363[医药卫生—病理学]