Oncotarget

Research Papers:

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

MaKendra Umstead _, Jinglin Xiong, Qi Qi, Yuhong Du and Haian Fu

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Oncotarget. 2017; 8:28359-28372. https://doi.org/10.18632/oncotarget.15049

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Abstract

MaKendra Umstead1,2, Jinglin Xiong2,3, Qi Qi2, Yuhong Du2, Haian Fu2,4

1Graduate Program in Cancer Biology, Emory University, Atlanta, GA, USA

2Department of Pharmacology and Emory Chemical Biology Discovery Center, Emory University School of Medicine, Atlanta, GA, USA

3Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China

4Winship Cancer Institute, Atlanta, GA, USA

Correspondence to:

Haian Fu, email: hfu@emory.edu

Keywords: Aurora A, Ras, Raf, MAPK, protein-protein interactions

Received: September 14, 2016     Accepted: January 07, 2017     Published: February 03, 2017

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.


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