Abstract 3456: Molecular mechanisms of RSK2-ELK3 signaling axis in neoplastic cell transformation

Abstract

Abstract Constitutive active Ras mutation (RasG12V) plays a key role in cell proliferation and transformation in many solid human cancers. RSK2, a member of p90RSK superfamily, controlled by ERKs is an intermediate signaling molecule transducing Ras activation signal to downstream substrates including transcription factors, epigenetic factors and some kinases. Since RSK2 shows wide range of substrate spectrum, identification of RSK2's novel substrates is important to understand the role of RSK2 in cancer. We found that ELKs including ELK1, ELK3 and ELK4 are novel interaction partners of RSK2 by mammalian two-hybrid assay. In vitro kinase assay and immunoprecipitation assay indicated that ELK3 is a major binding partner of RSK2. Luciferase reporter assay demonstrated that ELK3 transactivation activity was increased by RSK2, resulted in the increase of c-fos promoter activity. Importantly, constitutive active (CA)-RasG12V-mediated foci formation in NIH3T3 cells were more increased by ectopic co-expression of CA-RasG12V and RSK2. Additionally, signaling blockage of the CA-RasG12V/ELK3 by RSK2 knockdown suppressed foci formation. These results demonstrated that RSK2-ELK3 signaling axis plays an important role in RasG12V-mediated neoplastic cell transformation. Key words : MAPK, RSK2, ELKs, cell proliferation, cell transformation Citation Format: Seon-Yeon Cho, Cheol-Jung Lee, Sun-Mi Yoo, Seung-Min Kim, Juhee Park, Yong-Yeon Cho. Molecular mechanisms of RSK2-ELK3 signaling axis in neoplastic cell transformation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3456.