Death receptor 5, a new member of the TNFR family, and DR4 induce FADD-dependent apoptosis and activate the NF-kappaB pathway.
Death receptor 4 (DR4) is a recently described receptor for the cytotoxic ligand TRAIL that reportedly uses a FADD-independent pathway to induce apoptosis and does not activate the NF-kappaB pathway. We have isolated a new member of the tumor necrosis factor receptor (TNFR) family, designated DR5, which bears a high degree of sequence homology to DR4. However, contrary to the previous reports, both DR4- and DR5-induced apoptosis can be blocked by dominant-negative FADD, and both receptors can activate NF-kappaB using a TRADD-dependent pathway. Finally, both receptors can interact with FADD, TRADD, and RIP. Thus, both DR5 and DR4 use FADD, TRADD, and RIP in their signal transduction pathways, and FADD is the common mediator of apoptosis by all known death domain-containing receptors.
Chaudhary
P M
PM
Department of Molecular Biotechnology, University of Washington, Seattle 98195, USA.
Eby
M
M
Jasmin
A
A
Bookwalter
A
A
Murray
J
J
Hood
L
L
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D002352:Carrier Proteins / Q000378:metabolism*; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D002460:Cell Line; D003001:Cloning, Molecular; D006224:Cricetinae; D003546:Cysteine Endopeptidases / Q000378:metabolism; D018076:DNA, Complementary; D053200:Fas-Associated Death Domain Protein; D006801:Humans; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D053219:Receptors, Tumor Necrosis Factor, Member 25; D017422:Sequence Analysis, DNA; D047990:TNF Receptor-Associated Factor 1; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018076:DNA, Complementary; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D016328:NF-kappa B; D011506:Proteins; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D053219:Receptors, Tumor Necrosis Factor, Member 25; D047990:TNF Receptor-Associated Factor 1; C105190:TNFRSF10A protein, human; C505639:TNFRSF10B protein, human; C506033:TNFRSF25 protein, human; C506249:RIPK1 protein, human; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D003546:Cysteine Endopeptidases