NRADD, a novel membrane protein with a death domain involved in mediating apoptosis in response to ER stress.
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.
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
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X
Wang
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Shao
F S
FS
Zetoune
M G
MG
Zeidler
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K
Gowrishankar
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Vincenz
D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000502:physiology*; D001665:Binding Sites / Q000235:genetics; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D006031:Glycosylation; D006367:HeLa Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D016716:PC12 Cells; D051381:Rats; D053218:Receptors, Death Domain; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014162:Transfection
D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C480683:Nradd protein, mouse; D053218:Receptors, Death Domain; D011993:Recombinant Fusion Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D020169:Caspases