The first two authors contributed equally to this paper.
Reticulon-1C acts as a molecular switch between endoplasmic reticulum stress and genotoxic cell death pathway in human neuroblastoma cells
Article first published online: 5 FEB 2007
Journal of Neurochemistry
Volume 102, Issue 2, pages 345–353, July 2007
How to Cite
Sano, F. D., Fazi, B., Tufi, R., Nardacci, R. and Piacentini, M. (2007), Reticulon-1C acts as a molecular switch between endoplasmic reticulum stress and genotoxic cell death pathway in human neuroblastoma cells. Journal of Neurochemistry, 102: 345–353. doi: 10.1111/j.1471-4159.2007.04479.x
- Issue published online: 5 FEB 2007
- Article first published online: 5 FEB 2007
- Received November 8, 2006; revised manuscript received January 10, 2007; accepted January 15, 2007.
- endoplasmic reticulum;
Damage or stress in many organelles may trigger apoptosis by several not yet fully elucidated mechanisms. A cell death pathway is induced by endoplasmic reticulum (ER) stress elicited by the unfolded protein response and/or by aberrant Ca2+ signalling. Reticulon-1C (RTN-1C) belongs to the reticulon family, neuroendocrine-specific proteins localized primarily on the ER membrane. In the present study, we demonstrate that RTN-1C is able to modulate, in a mutually exclusive way, the cellular sensitivity to different apoptosis pathways in human neuroblastoma cells. In fact, the increase of RTN-1C protein levels per se results in ER stress-induced cell death, mediated by an increase of cytosolic Ca2+, and significantly sensitizes cells to different ER stress inducers. In line with these findings, the reduction of RTN-1C, by antisense DNA expression, reduced the sensitivity to ER-stressors. In the presence of high RTN-1C levels, genotoxic drugs become ineffective as a consequence of the cytoplasm translocation of p53 protein, while the silencing of endogenous RTN-1C results in the potentiation of the genotoxic drugs action. These data indicate that RTN-1C is able to modulate the cellular sensitivity to different apoptotic pathways representing a promising molecular target for new drug development.