Journal
CELL DEATH AND DIFFERENTIATION
Volume 10, Issue 5, Pages 580-591Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.cdd.4401208
Keywords
death receptors; apoptosis; caspases; endoplasmatic reticulum
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Funding
- NIEHS NIH HHS [ES08111] Funding Source: Medline
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NRADD (neurotrophin receptor alike death domain protein) is a novel protein with transmembrane and cytoplasmic regions highly homologous to death receptors, particularly p75(NTR). However, the short N-terminal domain is unique. Expression of NRADD induced apoptosis in a number of cell lines. The apoptotic mechanism involved the activation of caspase-8 and execution of apoptosis without requiring mitochondrial components. The activation of this death receptor-like mechanism required the N-terminal domain, which is N-glycosylated and needed for subcellular targeting. Deletion of the N-terminal domain produced a dominant-negative form of NRADD that protected neurons and Schwann cells from a variety of endoplasmic reticulum (ER) stressors. NRADD may therefore be a necessary component for generating an ER-induced proapoptotic signal.
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