First published online May 21, 2007
Journal of Cell Science 120, 1103e (2007)
© The Company of Biologists Limited
Neuronal life-saver eNRAGEd
Balancing cell division and cell death is essential for normal tissue growth during development and is controlled by a dynamic protein-protein interaction network. One pair of interacting proteins that regulates this balance during neuronal development, suggest Claudio Passananti and colleagues on p. 1852, is NRAGE (neurotrophin-receptor-interacting MAGE homolog) and Che-1, an apoptosis-antagonising transcription factor. NRAGE, which contains a C-terminal melanoma-associated antigen (MAGE) homology domain, has been identified as a pro-apoptotic molecule during neuronal development whereas Che-1 has anti-apoptotic activity in cortical neurons. The authors use two-hybrid analysis to reveal the interaction between NRAGE and the C-terminal domain of Che-1. They then show that NRAGE sequesters Che-1 in the cytoplasm and targets it for proteasome-dependent degradation. Finally, they report that Che-1 overexpression prevents NRAGE-induced cell death in vitro in neuronal cells. The authors suggest, therefore, that NRAGE and Che-1 act as executors of opposing programs that ensure commitment to cell death or survival, respectively, during neuronal development.
Related articles in JCS:
- NRAGE associates with the anti-apoptotic factor Che-1 and regulates its degradation to induce cell death
- Maria Grazia Di Certo, Nicoletta Corbi, Tiziana Bruno, Simona Iezzi, Francesca De Nicola, Agata Desantis, Maria Teresa Ciotti, Elisabetta Mattei, Aristide Floridi, Maurizio Fanciulli, and Claudio Passananti
JCS 2007 120: 1852-1858.
[Abstract]
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