Abstract 1791: RADIL regulates RAS downstream signaling

Abstract RAS proteins regulate a variety of cellular processes including cell survival, proliferation, and differentiation. RAS genes are among the most frequently mutated oncogenes in human malignancies. To date, there are no successful anti-cancer drugs in the clinic that target RAS proteins or their pathways. Therefore, it is imperative to identify and characterize new components that regulate RAS activity or mediates its downstream signaling. Recently, we identified a series of proteins that are associated with HRAS using a combination of immunoprecipitation and mass spectrometry. We first focused on RADIL, a gene product with Ras-Association (RA) and DIL domains. RADIL is known to be a downstream effector of RAP1, inhibiting RhoA signaling in the regulation of cell survival, adhesion, and migration. We demonstrated that RADIL interacted with all three isoforms of RAS, including H, N, and KRAS. Interestingly, constitutively active HRAS (HRASG12V) was strongly associated with RADIL whereas dominant negative HRAS (HRASS17N) displayed a compromised association with RADIL, suggesting that RADIL may be required for RAS activation. We also found that Radil Knockout cells had weakened ERK phosphorylation whereas induced expression of RADIL promoted ERK phosphorylation, suggesting that RADIL is required for the RAS-MEK-ERK signaling cascade in vitro. Taken together, our current studies strongly suggest that RADIL may be important for regulating RAS signaling. Citation Format: Byeong Hyeok Choi, Ziyue Kou, Mark R. Philips, Wei Dai. RADIL regulates RAS downstream signaling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1791.