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.
Wu
M Y
MY
Department of Microbiology and Immunology, National Yang-Ming University School of Medicine, Taipei 11221, Taiwan.
Wang
P Y
PY
Han
S H
SH
Hsieh
S L
SL
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001483:Base Sequence; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism*; D017931:DNA Primers; D006367:HeLa Cells; D006801:Humans; D053259:Lymphotoxin beta Receptor; D008856:Microscopy, Fluorescence; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D015398:Signal Transduction
D015853:Cysteine Proteinase Inhibitors; D017931:DNA Primers; C505697:LTBR protein, human; D053259:Lymphotoxin beta Receptor; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins