Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
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Target Concepts:
Gene/Protein
Disease
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Enzyme
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Query: EC:3.4.22.62 (
caspase-9
)
7,507
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Decoy receptor 3
(
DcR3
)/TR6/M68 is a soluble receptor that binds to the Fas ligand LIGHT and TL1A. Elevated levels of
DcR3
expression have been found in many tumors. We report an unexpected effect of
DcR3
by sensitizing Jurkat and U937 cells to apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Cell death triggered by anti-Fas and tumor necrosis factor was unaffected by
DcR3
.
DcR3
by itself did not stimulate apoptosis. The ability to augment TRAIL-initiated cell death was not observed with soluble lymphotoxin beta receptor or soluble death receptor 3, indicating that binding to LIGHT or TL1A alone is insufficient to trigger TRAIL sensitivity. Incubation with
DcR3
did not increase the surface expression of TRAIL receptor, and the level of Fas-associated death domain protein and cellular FLICE-like inhibitory protein was not altered. Instead, in the presence of
DcR3
, TRAIL engagement resulted in an increased activation of caspase-8, an elevated cleavage of Bid, and enhanced release of Smac and cytochrome c from mitochondria to cytosol compared with TRAIL alone. This led to increased activation of
caspase-9
and caspase-3. The unusual ability of
DcR3
to promote TRAIL-triggered death may be used to potentiate TRAIL efficacy during treatment tumors overexpressing
DcR3
.
...
PMID:Sensitization of cells to TRAIL-induced apoptosis by decoy receptor 3. 1547 69
To investigate the correlation between sensitivity to Fas ligand (FasL) and expression level of
decoy receptor 3
(
DcR3
) on tumor cell surface, Fas/
DcR3
mRNA expression was detected by RT-PCR. Anti-
DcR3
mAb was used to detect expression level of
DcR3
on surface of tumor cells by flow cytometry. Caspase-8,
caspase-9
, caspase-3, Bcl-2 expressions were analyzed by Western blot, respectively. Sensitivity to apoptosis induced by FasL was determined by Annexin V apoptosis kit. The expressions of
DcR3
on the surface of tumor cells from high to low were approximately 35.3% in BGC823 cells, and 21.6% in MCF-7 cells, respectively. The apoptotic rates induced by FasL from low to high were 15.6% in BGC823 cells, and 58.2% in MCF-7 cells, respectively. There was a significant correlation between the expression levels of
DcR3
with FasL-inducing apoptosis.
...
PMID:Correlation between expression of DcR3 on tumor cells and sensitivity to FasL. 1816 57
