Journal
ONCOTARGET
Volume 8, Issue 17, Pages 28359-28372Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.15049
Keywords
Aurora A; Ras; Raf; MAPK; protein-protein interactions
Categories
Funding
- NIH NCI [U01CA168449]
- Georgia Research Alliance
- Winship Cancer Institute NIH [5P30CA138292]
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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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