RRC ID 1596
Author Tamura K, Noyama T, Ishizawa YH, Takamatsu N, Shiba T, Ito M.
Title Xenopus death receptor-M1 and -M2, new members of the tumor necrosis factor receptor superfamily, trigger apoptotic signaling by differential mechanisms.
Journal J Biol Chem
Abstract Signaling through the tumor necrosis factor receptor (TNFR) superfamily can lead to apoptosis or promote cell survival, proliferation, and differentiation. A subset of this family, including TNFR1 and Fas, signals cell death via an intracellular death domain and therefore is termed the death receptor (DR) family. In this study, we identified new members of the DR family, designated xDR-M1 and xDR-M2, in Xenopus laevis. The two proteins, which show high homology (71.7% identity), have characteristics of the DR family, that is, three cysteine-rich domains, a transmembrane domain, and a death domain. To elucidate how members of xDR-M subfamily regulate cell death and survival, we examined the intracellular signaling mediated by these receptors in 293T and A6 cells. Overexpression of xDR-M2 induced apoptosis and activated caspase-8, c-Jun N-terminal kinase, and nuclear factor-kappaB, although its death domain to a greater extent than did that of xDR-M1 in 293T cells. A caspase-8 inhibitor potently blocked this apoptosis induced by xDR-M2. In contrast, xDR-M1 showed a greater ability to induce apoptosis through its death domain than did xDR-M2 in A6 cells. Interestingly, a general serine protease inhibitor, but not the caspase-8 inhibitor, blocked the xDR-M1-induced apoptosis. These results imply that activation of caspase-8 or serine protease(s) may be required for the xDR-M2- or xDR-M1-induced apoptosis, respectively. Although xDR-M1 and xDR-M2 are very similar to each other, the difference in their death domains may result in diverse signaling, suggesting distinct roles of xDR-M1 and xDR-M2 in cell death or survival.
Volume 279(9)
Pages 7629-35
Published 2004-2-27
DOI 10.1074/jbc.M306217200
PII S0021-9258(18)44461-4
PMID 14668340
MeSH Amino Acid Sequence Animals Apoptosis* / drug effects Caspase 8 Caspase Inhibitors Caspases / metabolism Cell Line Cell Survival Cysteine Enzyme Activation Enzyme Inhibitors / pharmacology Gene Expression Humans JNK Mitogen-Activated Protein Kinases Mitogen-Activated Protein Kinases / metabolism Molecular Sequence Data NF-kappa B / metabolism Receptors, Cell Surface / chemistry Receptors, Cell Surface / genetics Receptors, Cell Surface / physiology* Reverse Transcriptase Polymerase Chain Reaction Sequence Homology Signal Transduction* Transfection Xenopus Proteins / chemistry Xenopus Proteins / genetics Xenopus Proteins / physiology* Xenopus laevis* fas Receptor / pharmacology
IF 4.238
Times Cited 18
DNA material pRx-crmA-bsr (RDB01890)