Revealing A-Raf functions through its interactome

• Published in: Biochimica et biophysica acta. Proteins and proteomics Vol. 1866; no. 8; pp. 849 - 856
• Main Authors: Zhang, Xin-Yu, Guo, Hui, Han, Bing, Zhang, Xu-Min, Huang, Ying, Yang, Yang, Liu, Ying, Guo, Xiao-Xi, Hao, Qian, An, Su, Xu, Tian-Rui
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2018
• Subjects: A-Raf; Apoptosis; Blotting, Western; Cancer; Carcinogenesis - genetics; Cell Adhesion; Cell signaling; GTP Phosphohydrolases - metabolism; HEK293 Cells; Humans; Immunoprecipitation; Interacting protein; Protein Interaction Domains and Motifs; Proteomics; Proto-Oncogene Proteins A-raf - genetics; Proto-Oncogene Proteins A-raf - metabolism; RNA - metabolism; Signal Transduction; A-Raf; Interacting protein; Cell signaling; Cancer
• ISSN: 1570-9639; 1878-1454
• DOI: 10.1016/j.bbapap.2018.05.009

A-Raf is a member of the Raf kinase family. Unlike B-Raf and C-Raf, the functions of A-Raf remain obscure. To gain more insight into the biological functions of A-Raf, we investigated the A-Raf interactome using proteomics. We found 132 proteins that interact with A-Raf and confirmed the interaction of 12 of these proteins with A-Raf by western blotting. Our data suggested that A-Raf regulates apoptosis, RNA catabolism, GTPase activity, and cell adhesion by interacting with proteins located in different cellular compartments. We identified all ten hallmarks of cancer in these interacting proteins, suggesting that A-Raf is involved in carcinogenesis. Our results also indicated that A-Raf may play a role in different diseases and signaling pathways. These findings have identified potential regulators of A-Raf and provide a systemic insight into its biological functions. •The identification and comparison of A-Raf and A-Raf Y296R interactomes.•GO analysis of A-Raf interactome suggests that A-Raf may be involved in apoptosis, cell adhesion and so.•All ten hallmarks of cancers are identified in the interactome of A-Raf.•The comparison of the three Raf kinases (A-Raf, B-Raf and C-Raf) interactomes.