Aurora kinase A interacts with H-Ras and potentiates Ras-MAPK signaling

• Type of Material: Article
• Authors: MaKendra Umstead, Emory University; Jinglin Xiong, Emory University; Qi Qi, Emory University; Yuhong Du, Emory University; Haian Fu, Emory University
• Language: English
• Date: 2017-04-25
• Publisher: Impact Journals
• Publication Version: Final Published Version
• Copyright Statement: © 2017 Umstead et al.
• License: Creative Commons Attribution 3.0 IGO License
• Final Published Version (URL): http://dx.doi.org/10.18632/oncotarget.15049
• Title of Journal or Parent Work: Oncotarget
• ISSN: 1949-2553
• Volume: 8
• Issue: 17
• Start Page: 28359
• End Page: 28372
• Grant/Funding Information: This research was supported by NIH NCI U01CA168449, Georgia Research Alliance, and Winship Cancer Institute NIH 5P30CA138292.
• Keywords: Cell Biology; Aurora A; Ras; protein-protein interactions; Oncology; Raf; Life Sciences & Biomedicine; MAPK; Science & Technology
• Research Categories: Health Sciences, Oncology; Biology, Molecular

Abstract

In cancer, upregulated Ras promotes cellular transformation and proliferation in part through activation of oncogenic Ras-MAPK signaling. While directly inhibiting Ras has proven challenging, new insights into Ras regulation through protein-protein interactions may offer unique opportunities for therapeutic intervention. Here we report the identification and validation of Aurora kinase A (Aurora A) as a novel Ras binding protein. We demonstrate that the kinase domain of Aurora A mediates the interaction with the N-terminal domain of H-Ras. Further more, the interaction of Aurora A and H-Ras exists in a protein complex with Raf-1. We show that binding of H-Ras to Raf-1 and subsequent MAPK signaling is enhanced by Aurora A, and requires active H-Ras. Thus, the functional linkage between Aurora A and the H-Ras/Raf-1 protein complex may provide a mechanism for Aurora A's oncogenic activity through direct activation of the Ras/MAPK pathway.