Overexpression of Par-4 Sensitizes TRAIL-Induced Apoptosis Via Inactivation of NF-kappa B and Akt Signaling Pathways in Renal Cancer Cells

Title
Overexpression of Par-4 Sensitizes TRAIL-Induced Apoptosis Via Inactivation of NF-kappa B and Akt Signaling Pathways in Renal Cancer Cells
Author(s)
이태진노효정[노효정]장지훈[장지훈]박은정[박은정]최경숙[최경숙]권택규[권택규]
Keywords
TUMOR-NECROSIS-FACTOR; PROTEIN-KINASE-C; PROSTATE-CANCER; BCL-2 EXPRESSION; SUPPRESSION; RECEPTOR; LIGAND; GENE; INDUCTION; SURVIVAL
Issue Date
201004
Publisher
WILEY-LISS
Citation
JOURNAL OF CELLULAR BIOCHEMISTRY, v.109, no.5, pp.885 - 895
Abstract
The prostate-apoptosis-response-gene-4 (Par-4) is up-regulated in prostate cells undergoing programmed cell death. Furthermore. Par-4 protein has been shown to function as an effector of cell death in response to various apoptotic stimuli that trigger mitochondria and membrane receptor-mediated cell death pathways. In this study, we investigated how Par-4 modulates TRAIL-mediated apoptosis in TRAIL-resistant Caki cells. Par-4 overexpressing cells were strikingly sensitive to apoptosis induced by TRAIL compared with control cells. Par-4 overexpressing Caki cells treated with TRAIL showed an increased activation of the initiator caspase-8 and the effector caspase-3, together with an enforced cleavage of XIAP and c-FLIP. TRAIL-induced reduction of XIAP and c-FLIP protein levels in Par-4 overexpressing cells was prevented by z-VAD pretreatment. In addition, the surface DR5 protein level was increased in TRAIL-treated Par-4 overexpressing cells. Interestingly, even though a deletion of leucine zipper domain in Par-4 recovered Bcl-2 level to basal level induced by wild type Par-4, it partly decreased sensitivity to TRAIL in Caki cells. In addition, exposure of Caki/Par-4 cells to TRAIL led to reduction of phosphorylated Akt levels, but deletion of leucine zipper domain of Par-4 did not affect these phosphorylated Akt levels. In conclusion, we here provide evidence that ectopic expression of Par-4 sensitizes Caki cells to TRAIL via modulation of multiple targets, including DR5, Bcl-2, Akt, and NF-kappa B. J. Cell. Biochem. 109: 885-895, 2010. (C) 2010 Wiley-Liss, Inc.
URI
http://hdl.handle.net/YU.REPOSITORY/22648http://dx.doi.org/10.1002/jcb.22504
ISSN
0730-2312
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의과대학 > 해부학교실 > Articles
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