The role of apoptosis signal-regulating kinase 1 in lymphotoxin-beta receptor-mediated cell death
Resource
THE JOURNAL OF BIOLOGICAL CHEMISTRY 278(18),16073-16081
Journal
The Journal of Biological Chemistry
Pages
16073-16081
Date Issued
2003
Date
2003
Author(s)
Chen, Mei-Chieh
Hwang, Ming-Jing
Chou, Yang-Chieh
Chen, Wei-Hsu
Cheng, Genhong
Nakano, Hiroyasu
Mai, Shen-Chih
DOI
246246/2006111501211894
Abstract
LIGHT (homologous to lymphotoxins, shows inducible expression, and competes with herpes simplex virus glycoprotein D for herpesvirus entry mediator, a receptor expressed by T lymphocytes) is a member of the tumor necrosis factor superfamily that can interact with lymphotoxin-beta receptor (LTbetaR), herpes virus entry mediator, and decoy receptor (DcR3). In our previous study, we showed that LIGHT is able to induce cell death via the non-death domain containing receptor LTbetaR to activate both caspase-dependent and caspase-independent pathway. In this study, a LIGHT mutein, LIGHT-R228E, was shown to exhibit similar binding specificity as wild type LIGHT to LTbetaR, but lose the ability to interact with herpes virus entry mediator. By using both LIGHT-R228E and agonistic anti-LTbetaR monoclonal antibody, we found that signaling triggered by LTbetaR alone is sufficient to activate both caspase-dependent and caspase-independent pathways. Cross-linking of LTbetaR is able to recruit TRAF3 and TRAF5 to activate ASK1, whereas its activity is inhibited by free radical scavenger carboxyfullerenes. The activation of ASK1 is independent of caspase-3 activation, and kinase-inactive ASK1-KE mutant can inhibit LTbetaR-mediated cell death. This suggests that ASK1 is one of the factors involved in the caspase-independent pathway of LTbetaR-induced cell death.
SDGs
Type
journal article
File(s)![Thumbnail Image]()
Loading...
Name
7085.pdf
Size
662.13 KB
Format
Adobe PDF
Checksum
(MD5):04960ab60f042111d837404afb821ea7