Over-expression of Reticulon 3 (RTN3) enhances TRAIL-mediated apoptosis via up-regulation of death receptor 5 (DR5) and down-regulation of c-FLIP

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Title
Over-expression of Reticulon 3 (RTN3) enhances TRAIL-mediated apoptosis via up-regulation of death receptor 5 (DR5) and down-regulation of c-FLIP
Author(s)
J T Lee; T J Lee; C H Kim; Nam-Soon Kim; T K Kwon
Bibliographic Citation
Cancer Letters, vol. 279, no. 2, pp. 185-192
Publication Year
2009
Abstract
Reticulons (RTNs) are a group of integral membrane proteins that have no homology to other known apoptosis-related domains. Herein, we found that RTN3 overexpressing Caki cells were sensitive to TRAIL-mediated apoptosis. RTN3-induced down-regulation of c-FLIP was recovered by pan-caspase inhibitor, z-VAD to basal levels in TRAIL-treated cells. The forced expression of c-FLIP attenuated the TRAIL-mediated apoptosis in RTN3 overexpressing cells. In addition, RTN3 over-expression provoked the enhanced protein levels in DR4 and DR5 as well as levels in DR5 surface protein but slight increase in DR4 surface protein. RTN3-mediated enhancement of TRAIL-induced apoptosis was markedly blocked by the DR5/Fc chimera or DR5 siRNA, indicating that the sensitization by RTN3 was mainly mediated through interactions of TRAIL with its receptors, DR5. Over-expression of RTN3 also enhanced TNF-a and Fas-mediated apoptosis. Taken together, over-expression of RTN3 might increase DR5 surface protein and concomitantly more activate caspase pathways, which cause the c-FLIP cleavage and enhancement of TRAIL-mediated apoptosis.
Keyword
RTN3TRAILapoptosisDR5c-FLIP
ISSN
0304-3835
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.canlet.2009.01.035
Type
Article
Appears in Collections:
Division of Biomedical Research > Rare Disease Research Center > 1. Journal Articles
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