p19(ras) is an alternative splicing product of the proto-oncogene c-H-ras pre-mRNA. In this study, we identified a novel p19(ras)-binding protein, Neuron-Specific Enolase (NSE), using the yeast two-hybrid method. NSE is one of the enolase families that convert 2-phospho-d-glycerate (PGA) to phosphoenolpyruvate (PEP) in the glycolysis pathway. In both endogenous and over-expressed systems, we confirmed interactions between p19(ras) and NSE via co-immunoprecipitation assay. We also identified the interaction region of p19(ras), which is required for binding with NSE. When full-length p19(ras) and C-terminal region are bound to NSE, it inhibits the enzymatic activity of NSE. Furthermore, p19(ras) interacted with Enolase alpha (Enoalpha) and repressed its enzymatic activity in vitro. p19(ras) repressed lung cancer cell proliferation mostly increased by NSE in H1299 cells. Taken together, these results suggest that p19(ras) is a novel regulator to suppress cell proliferation in lung cancer through the interaction with NSE.
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