遗传 >

2018 , Vol. 40 >Issue 1: 12 - 21

DOI: https://doi.org/10.16288/j.yczz.17-343

综述

TBC蛋白家族成员在人类疾病发生发展中的作用

展开
  • 1. 广西医科大学研究生院,南宁 530021
    2. 军事科学院军事医学研究院辐射医学研究所,蛋白质组学国家重点实验室,国家蛋白质科学中心(北京),北京 100850

收稿日期: 2017-10-22

  修回日期: 2017-12-12

  网络出版日期: 2017-12-22

基金资助

国家自然科学基金资助(81401981)

收起

The critical roles of TBC proteins in human diseases

Expand
  • 1. Graduate School, Guangxi Medical University, Nanning 530021, China
    2. National Center for Protein Sciences, the State Key Lab of Proteomics, Beijing Institute of Radiation Medicine, Beijing 100850, China

Received date: 2017-10-22

  Revised date: 2017-12-12

  Online published: 2017-12-22

Supported by

the National Science Foundation of China(81401981)

Fold

摘要

TBC(Tre-2/Bub2/Cdc16)是真核生物中普遍存在的一种由200个氨基酸残基组成的保守性蛋白质结构域,含有该结构域的蛋白质被称为TBC蛋白。TBC蛋白具有GTPase激活活性,可促进小G蛋白Rab-GTP水解为Rab-GDP,从而参与特异的胞内转运过程。在哺乳动物中,部分TBC蛋白具有十分重要的作用,其功能异常与人类疾病的发生发展密切相关。本文主要介绍了哺乳动物TBC蛋白的结构和功能,以及近年来TBC蛋白在人类疾病发生发展中的作用,以期为深入解析TBC蛋白的致病机制提供参考。

关键词： Rab; TBC; GTP酶激活蛋白; 转运

本文引用格式

施梦婷, 张莹, 周钢桥 . TBC蛋白家族成员在人类疾病发生发展中的作用[J]. 遗传, 2018 , 40(1) : 12 -21 . DOI: 10.16288/j.yczz.17-343

Abstract

The Tre-2/Bub2/Cdc16 (TBC) domain is a conserved protein motif consisting of approximately 200 amino acids, and is present in many eukaryotic proteins. TBC domain-containing proteins (TBC proteins) function as GTPase activating proteins (GAPs) for the small GTPase Rab, which can promote the hydrolysis of Rab-GTP to Rab-GDP in regulation of specific intracellular trafficking pathways. Several TBC proteins play important roles in cellular functions in mammals, and defects of which are closely associated with numerous disease processes. In this review, we summarize the structures and functions of the mammalian TBC proteins and recent advances in understanding their critical roles in the development of human diseases. This review serves as a reference for further investigations on the functions of TBC proteins in disease pathogeneses.

Key words： Rab; TBC; GTPase activating protein; trafficking

参考文献

[1] Tzeng HT, Wang YC. Rab-mediated vesicle trafficking in cancer. J Bio Med, 2016, 23(1): 70.
[2] Richardson PM, Zon LI. Molecular cloning of a cDNA with a novel domain present in the tre-2 oncogene and the yeast cell cycle regulators BUB2 and cdc16. Oncogene, 1995, 11(6): 1139-1148.
[3] Pan X, Eathiraj S, Munson M, Lambright DG. TBC- domain GAPs for Rab GTPases accelerate GTP hydrolysis by a dual-finger mechanism. Nature, 2006, 442(7100): 303-306.
[4] Chen YN, Gu X, Zhou XE, Wang W, Cheng D, Ge Y, Ye F, Xu HE, Lv Z. Crystal structure of TBC1D15 GTPase-activating protein (GAP) domain and its activity on Rab GTPases. Protein Sci, 2017, 26(4): 834-846.
[5] Frasa MA, Maximiano FC, Smolarczyk K, Francis RE, Betson ME, Lozano E, Goldenring J, Seabra MC, Rak A, Ahmadian MR. Armus is a Rac1 effector that inactivates Rab7 and regulates E-cadherin degradation. Curr Biol, 2010, 20(3): 198-208.
[6] Kanno E, Ishibashi K, Kobayashi H, Matsui T, Ohbayashi N, Fukuda M. Comprehensive screening for novel rab-binding proteins by GST pull-down assay using 60 different mammalian Rabs. Traffic, 2010, 11(4): 491-507.
[7] Eitzen G, Will E, Gallwitz D, Haas A, Wickner W. Sequential action of two GTPases to promote vacuole docking and fusion. EMBO J, 2000, 19(24): 6713-6720.
[8] Brett CL, Plemel RL, Lobingier BT, Vignali M, Fields S, Merz AJ. Efficient termination of vacuolar Rab GTPase signaling requires coordinated action by a GAP and a protein kinase. J Cell Biol, 2008, 182(6): 1141-1151.
[9] Lanzetti L, Rybin V, Malabarba MG, Christoforidis S, Scita G, Zerial M, Di Fiore PP. The Eps8 protein coordinates EGF receptor signalling through Rac and trafficking through Rab5. Nature, 2000, 408(6810): 374-377.
[10] Fuchs E, Haas AK, Spooner RA, Yoshimura S, Lord JM, Barr FA. Specific Rab GTPase-activating proteins define the Shiga toxin and epidermal growth factor uptake pathways. J Cell Biol, 2007, 177(6): 1133-1143.
[11] Haas AK, Fuchs E, Kopajtich R, Barr FA. A GTPase-activating protein controls Rab5 function in endocytic trafficking. Nat Cell Biol, 2005, 7(9): 887-893.
[12] Meyre D, Farge M, Lecoeur C, Proenca C, Durand E, Allegaert F, Tichet J, Marre M, Balkau B, Weill J, Delplanque J, Froguel P. R125W coding variant in TBC1D1 confers risk for familial obesity and contributes to linkage on chromosome 4p14 in the French population. Hum Mol Genet, 2008, 17(12): 1798-1802.
[13] Peck GR, Chavez JA, Roach WG, Budnik BA, Lane WS, Karlsson HK, Zierath JR, Lienhard GE. Insulin-stimulated phosphorylation of the Rab GTPase-activating protein TBC1D1 regulates GLUT4 translocation. J Biol Chem, 2009, 284(44): 30016-30023.

/

〈 〉

www.chinagene.cn
备案号：京ICP备09063187号-4
总访问:,今日访问:,当前在线:

版权所有 © 中国科学院遗传与发育生物学研究所 中国遗传学会
地址：北京市朝阳区北辰西路1号院　中国科学院遗传与发育生物学研究所1号楼　
邮政编码：100101
联系电话：010-64807669
E-mail：yczz@genetics.ac.cn