Prenylated Rab acceptor RABAC1 inhibits anti-apoptotic protein BCL2A1 and induces apoptosis

Abstract

The B cell lymphoma 2 (BCL2) family of proteins constitutes a critical intracellular checkpoint in the intrinsic apoptosis pathway. Among BCL2 members, the anti-apoptotic protein BCL2A1 mediates the resistance to BCL2 inhibitors and may be considered as a target for anti-cancer therapy. Here, we report that prenylated Rab acceptor 1 (RABAC1 or PRA1) inhibits the anti-apoptotic activity of BCL2A1 and induces apoptosis in AGS gastric cancer cells. Protein interaction of BCL2A1 and RABAC1 was verified by an in-vitro glutathione-S-transferase pull-down assay, immunoprecipitation, and confocal microscopy. When apoptosis was induced by cisplatin, the anti-apoptotic activity of BCL2A1 was blocked by RABAC1 expression. RABAC1 caused caspase-3 activation and decreased cell proliferation, clonogenic cell survival, and cell migration and invasion. We suggest RABAC1 as a potential therapeutic target for BCL2A1-related cancer.