HECAT5 regulates cell proliferation via interaction with M3R in cell type-specific manner

Abstract

Embryonic stem (ES) cells are derived from pluripotent inner cell mass of the early mammalian embryo. Their self-renewal and pluripotency make them attractive sources for stem cell therapies. For ethical and practical reasons, ES cells have a major threat limiting in potential therapeutic applications. To investigate the mechanism regulating stemness, especially cell cycle of ES cells, our previous study identified HECAT5 which is co-expressed in both ES and cancer cells, but not normal tissues by using Digital Differential Display (DDD).

Overexpression of HECAT5 promotes self-renewal capacity and it enhances tumorigenicity in cell type-specific manner. HECAT5 has effects on those through the interaction with M3R (Muscarinic acetylcholine receptor 3), candidate interacting partner of HECAT5, as modulators of M3R activities regulate cell proliferation in a HECAT5-dependent manner. In addition, overexpressed HECAT5 have different effects on the phosphorylation level of M3R in each cell types. In F3 cells, phosphorylation level of M3R was relatively low but HECAT5 enhanced its level. Meanwhile, in HEK293 cells, basically its level was high but HECAT5 decreased it. Besides, F3 and HEK293 cells showed different signaling pathways, ERK and AKT. Collectively, our study uncovers that a novel HECAT5 gene may play a role in regulating the stemness properties in cell type-specific manner.