中国细胞生物学学报 Chinese Journal of Cell Biology 2014, 36(8): 1162–1168DOI: 10.11844/cjcb.2014.08.0423

Raf-1激酶与肿瘤治疗

周厚庆 刘 莹 杨 洋 安 输 郭晓汐 徐天瑞*

(昆明理工大学生命科学与技术学院细胞信号传导实验室, 昆明 650500)

摘要 自Raf激酶被证明为逆转录病毒致癌基因的产物以来, 逐渐成为人们研究的热点。研究表明, Raf激酶既是Ras的效应物, 又能作为ERK信号通路中的重要组分, 成为活化的Ras和ERK之间的一个重要纽带。Ras-Raf-MEK-ERK信号通路参与了细胞增殖、分化和凋亡等生物学过程。作为这一信号通路上的节点蛋白, Raf激酶在肿瘤发生过程中起着关键作用。Raf家族成员Raf-1(c-Raf)在调控细胞运动和凋亡过程中发挥关键作用, 它既可以通过抑制促凋亡激酶ASK1和MST2活性来抑制细胞凋亡, 也可以通过激活Rok-α的活性来促进细胞迁移。该文主要综述了Raf-1激酶的调控机制及其在肿瘤发生过程中的作用, 同时也总结了以Raf-1为靶点的肿瘤治疗的最新进展。

关键词 Raf-MEK-ERK信号通路; Raf激酶; 肿瘤治疗; Raf-1; 凋亡; 细胞迁移

Raf-1 Kinase and Tumor Therapy

Zhou Houqing, Liu Ying, Yang Yang, An Shu, Guo Xiaoxi, Xu Tianrui*

(Cell Signaling Lab, Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China)

Abstract Since Raf kinases were identi ed as products of retroviroal oncogenes, the Raf kineses have been intensively studied. Raf kinases are not only the bona de effectors of the Ras, but also activators of the typi-cal ERK signaling pathway, which provide an important link between Ras and ERK. Ras-Raf-MEK-ERK signaling pathway is involved in many biological process including cell proliferation, differentiation and apoptosis. As a node of the Ras-Raf-MEK-ERK signaling pathway, Raf kinases play a crucial role in tumorgensis. Raf-1, a key member of Raf family, regulates cell motility by controlling the activity of Rok-α, and apoptosis by suppressing the activity of the proapoptosis kinases, ASK1 and MST2. In this review, we described the regulation of Raf-1 kinase and its role in the tumorgensis. We also summarized the latest development in tumor therapy targeting Raf-1.

Key words Ras-Raf-MEK-ERK signaling pathway; Raf kinases; tumor therapy; Raf-1; apoptosis; cell mobility

Raf激酶家族有3个成员: Raf-1/C-Raf、B-Raf和A-Raf。三个家族成员都与肿瘤发生相关。Raf-1是首先被验证的亚型[1], 它在调控生长因子信号通路的细胞效应方面发挥关键作用[2-4]。Raf-1能介导肿瘤细胞的增殖、分化和凋亡等多种生理过程, 对肿瘤的发生和发展有重要促进作用[5]。本文主要介绍

了Raf-1参与肿瘤发生的机制, 并综述了以Raf-1为靶点的肿瘤治疗的最新研究进展。

1 Raf-1的结构以及调控

1.1 Raf-1的结构

Raf激酶是由raf基因编码的蛋白产物, 其活化

收稿日期: 2013-12-18 接受日期: 2014-04-14

国家自然科学基金(批准号: U1302225)和云南省高端科技人才基金(批准号: 2012HA008)资助的课题*通讯作者。Tel: 0871-6593327, E-mail: xtrgfq@Received: December 18, 2013 Accepted: April 14, 2014　　

This work was supported by the National Natural Science Foundation of China (Grant No.U1302225) and High-End Technology Talents Foundation in Yunnan Province (Grant No.2012HA008)

*Corresponding author. Tel: +86-871-6593327, E-mail: xtrgfq@

网络出版时间: 2014-07-21 10:09 URL: /kcms/doi/10.11844/cjcb.2014.08.0423.html