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Lys63-linked polyubiquitination of BRAF at lysine 578 is required for BRAF-mediated signaling

Year: 2013
Type: article
Abstract: 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.
DOI: 10.1038/srep02344
Authors: Lei An, Wei Jia, Yang Yu, Ning Zou, Li Liang, Yanling Zhao, Yihui Fan, Jin Cheng, Zhongcheng Shi, Gufeng Xu, Grace Li, Jianhua Yang, Hong Zhang
Institutions: The University of Texas MD Anderson Cancer Center, Shihezi University, Harbin Medical University, Chinese Center For Disease Control and Prevention, Peking University Third Hospital, Baylor College of Medicine, Dan L Duncan Comprehensive Cancer Center, Peking University
Language: English
Open Access status: gold
Estimated APC paid: $2,690
OpenAlex ID: W2050723350
FWCI: 0.746
Cites: 30
Cited by: 14
Related to: 10