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

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Abstract

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 (p38MAPK) 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 p38MAPK and underwent apoptosis offering intriguing incite into NRAGE’s contribution in BMP apoptotic signaling.

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Acknowledgments

This work was supported by National Institutes of Health (NIH) grant R01NS055304 awarded to JMV and NIH Center of Biomedical Research Excellence (COBRE) P20RR018789 in Stem Cell Biology and Regenerative Medicine to Maine Medical Center (Portland, Maine). J.A.R. was funded by the Integrative Graduate Education Research Training (IGERT) Functional Genomics Ph.D. program through a fellowship from National Science Foundation grant 0221625 awarded to the University of Maine (Orono, Maine), Maine Medical Center Research Institute (Scarborough, Maine), and the Jackson Laboratory (Bar Harbor, Maine).

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Author notes

  1. Rebecca A. Cowling

    Present address: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Room 881, Toronto, ON, M5G 1X5, Canada

  2. Joshua S. Himmelfarb

    Present address: Department of Cognitive Sciences, Brown University, Box 1978, Providence, RI, 02912, USA

Authors and Affiliations

  1. IGERT Functional Genomics Ph.D. Program, University of Maine, 267A Engineering Science and Research Building/Barrows Hall, Orono, ME, 04469, USA

    Jennifer A. Rochira

  2. Department of Biochemistry, Microbiology, and Molecular Biology, University of Maine, 5735 Hitchner Hall, Orono, ME, 04469, USA

    Rebecca A. Cowling

  3. Maine Medical Center Research Institute, Center for Molecular Medicine, 81 Research Drive, Scarborough, ME, 04074, USA

    Jennifer A. Rochira, Rebecca A. Cowling, Joshua S. Himmelfarb, Tamara L. Adams & Joseph M. Verdi

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  1. Jennifer A. Rochira
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  2. Rebecca A. Cowling
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  3. Joshua S. Himmelfarb
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  4. Tamara L. Adams
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  5. Joseph M. Verdi
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Correspondence to Joseph M. Verdi.

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Rochira, J.A., Cowling, R.A., Himmelfarb, J.S. et al. Mapping of NRAGE domains reveals clues to cell viability in BMP signaling. Apoptosis 15, 63–70 (2010). https://doi.org/10.1007/s10495-009-0427-6

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