Mapping of NRAGE domains reveals clues to cell viability in BMP signaling.

Bone morphogenetic signaling (BMP) is a key pathway during neurogenesis and depends on many downstream intermediators to carry out its signaling. One such signaling pathway utilizes neurotrophin receptor-interacting MAGE protein (NRAGE), a member of the melanoma-associated antigen (MAGE) family, to upregulate p38 mitogen activated protein kinase (p38(MAPK)) in response to cellular stress and activate caspases which are critical in leading cells to death. NRAGE consists of two conserved MAGE homology domains separated by a unique hexapeptide repeat domain. Although we have previously implicated NRAGE in inducing apoptosis in neural progenitors and P19 cells, a model system for neural progenitors, its domains have yet to be explored in determining which one may be responsible for setting up the signaling for apoptosis. Here, we overexpressed a series of deletion mutations in P19 cells to show that only those with at least half of the repeat domain, activated p38(MAPK) and underwent apoptosis offering intriguing incite into NRAGE's contribution in BMP apoptotic signaling.