The cytoplasmic domain of the lymphotoxin-beta receptor mediates cell death in HeLa cells.
Activation of lymphotoxin-beta receptor (LT-betaR) by conjugation with heterotrimeric lymphotoxin, LT-alpha1/beta2, or by cross-linking with anti-LT-betaR antibodies can trigger apoptosis. We have observed that overexpression of either LT-betaR or the cytoplasmic domain of LT-betaR (LT-betaR(CD)) also induces apoptosis, which may be attributed to the tendency of LT-betaR(CD) to self-associate. The ... self-association domain of LT-betaR(CD) was mapped to amino acids 324-377, a region of the protein that is also essential for LT-betaR-induced apoptosis. Furthermore, we have shown that LT-betaR(CD)-induced apoptosis could be inhibited by a TRAF3 dominant negative mutant and by the caspase inhibitors Z-VAD-FMK, DEVD-FMK, and CrmA. The ligand-independent apoptosis induced by LT-betaR(CD) will help us to further dissect LT-betaR signaling pathway.
Mesh Terms:
Apoptosis, Base Sequence, Cysteine Proteinase Inhibitors, Cytoplasm, DNA Primers, Hela Cells, Humans, Lymphotoxin beta Receptor, Microscopy, Fluorescence, Receptors, Tumor Necrosis Factor, Recombinant Proteins, Sequence Deletion, Signal Transduction
Apoptosis, Base Sequence, Cysteine Proteinase Inhibitors, Cytoplasm, DNA Primers, Hela Cells, Humans, Lymphotoxin beta Receptor, Microscopy, Fluorescence, Receptors, Tumor Necrosis Factor, Recombinant Proteins, Sequence Deletion, Signal Transduction
J. Biol. Chem.
Date: Apr. 23, 1999
PubMed ID: 10207006
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