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Lys63-linked polyubiquitination of BRAF at lysine 578 is required for BRAF-mediated signaling
An, Lei1; Jia, Wei1,2; Yu, Yang1; Zou, Ning3; Liang, Li1,4; Zhao, Yanling1; Fan, Yihui5; Cheng, Jin5,6; Shi, Zhongcheng7; Xu, Gufeng5; Li, Grace5; Yang, Jianhua5; Zhang, Hong1
刊名SCIENTIFIC REPORTS
2013-08-02
DOI10.1038/srep02344
3
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Multidisciplinary Sciences
研究领域[WOS]Science & Technology - Other Topics
关键词[WOS]REGULATES AKT UBIQUITINATION ; THYROID-CARCINOMA ; RAS PROTEINS ; ACTIVATION ; KINASE ; CANCER ; PATHWAY ; TUMORIGENESIS ; SENSITIVITY ; INHIBITION
英文摘要

The RAF kinase family is essential in mediating signal transduction from RAS to ERK. BRAF constitutively active mutations correlate with human cancer development. However, the precise molecular regulation of BRAF activation is not fully understood. Here we report that BRAF is modified by Lys63-linked polyubiquitination at lysine 578 within its kinase domain once it is activated by gain of constitutively active mutation or epidermal growth factor (EGF) stimulation. Substitution of BRAF lysine 578 with arginine (K578R) inhibited BRAF-mediated ERK activation. Furthermore, ectopic expression of BRAF K578R mutant inhibited anchorage-independent colony formation of MCF7 breast cancer cell line. Our studies have identified a previously unrecognized regulatory role of Lys63-linked polyubiquitination in BRAF-mediated normal and oncogenic signalings.

语种英语
WOS记录号WOS:000322617900001
项目编号1R01NS072420
资助机构Fleming-Davenport Award from Texas Medical Center ; University of Texas MD Anderson Cancer Center ; University Cancer Foundation via the Institutional Research Grant program at the University of Texas MD Anderson Cancer Center ; NIH/NINDS
引用统计
被引频次:6[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/61140
专题北京大学第三临床医学院
北京大学第三临床医学院_肿瘤治疗中心
作者单位1.Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA
2.Shihezi Univ, Sch Med, Dept Pathol, Shihezi 832002, Xinjiang, Peoples R China
3.Harbin Med Univ, Chinese Ctr Dis Control & Prevent, Ctr Endem Dis Control, Harbin 150081, Heilongjiang, Peoples R China
4.Peking Univ, Hosp 3, Dept Tumor Chemotherapy & Radiat Sickness, Beijing 100191, Peoples R China
5.Baylor Coll Med, Dan L Duncan Canc Ctr, Dept Pediat, Texas Childrens Canc Ctr, Houston, TX 77030 USA
6.Peking Univ, Hlth Sci Ctr, Dept Microbiol, Beijing 100191, Peoples R China
7.Baylor Coll Med, Dan L Duncan Canc Ctr, Dept Pathol, Houston, TX 77030 USA
推荐引用方式
GB/T 7714
An, Lei,Jia, Wei,Yu, Yang,et al. Lys63-linked polyubiquitination of BRAF at lysine 578 is required for BRAF-mediated signaling[J]. SCIENTIFIC REPORTS,2013,3.
APA An, Lei.,Jia, Wei.,Yu, Yang.,Zou, Ning.,Liang, Li.,...&Zhang, Hong.(2013).Lys63-linked polyubiquitination of BRAF at lysine 578 is required for BRAF-mediated signaling.SCIENTIFIC REPORTS,3.
MLA An, Lei,et al."Lys63-linked polyubiquitination of BRAF at lysine 578 is required for BRAF-mediated signaling".SCIENTIFIC REPORTS 3(2013).
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