P19 ras Represses proliferation of non-small cell lung cancer possibly through interaction with Neuron-Specific Enolase (NSE)

Abstract

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 α (Enoα) 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.