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Overexpression of Par-4 sensitizes TRAIL-induced apoptosis via inactivation of NF-kappaB and Akt signaling pathways in renal cancer cells.

DC Field Value Language
dc.contributor.authorLee, TJ-
dc.contributor.authorJang, JH-
dc.contributor.authorNoh, HJ-
dc.contributor.authorPark, EJ-
dc.contributor.authorChoi, KS-
dc.contributor.authorKwon, TK-
dc.description.abstractThe 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-kappaB.-
dc.subject.MESHAntigens, CD95/metabolism-
dc.subject.MESHApoptosis/*drug effects-
dc.subject.MESHApoptosis Regulatory Proteins/chemistry/*metabolism-
dc.subject.MESHCASP8 and FADD-Like Apoptosis Regulating Protein/metabolism-
dc.subject.MESHCaspase 8/metabolism-
dc.subject.MESHCell Line, Tumor-
dc.subject.MESHEnzyme Activation/drug effects-
dc.subject.MESHKidney Neoplasms/enzymology/*pathology-
dc.subject.MESHLeucine Zippers-
dc.subject.MESHNF-kappa B/*metabolism-
dc.subject.MESHPhosphorylation/drug effects-
dc.subject.MESHProtein Structure, Tertiary-
dc.subject.MESHProto-Oncogene Proteins c-akt/*metabolism-
dc.subject.MESHReceptors, Death Domain/metabolism-
dc.subject.MESHSequence Deletion-
dc.subject.MESHSignal Transduction/*drug effects-
dc.subject.MESHTNF-Related Apoptosis-Inducing Ligand/*pharmacology-
dc.subject.MESHTumor Necrosis Factor-alpha/pharmacology-
dc.subject.MESHX-Linked Inhibitor of Apoptosis Protein/metabolism-
dc.titleOverexpression of Par-4 sensitizes TRAIL-induced apoptosis via inactivation of NF-kappaB and Akt signaling pathways in renal cancer cells.-
dc.contributor.affiliatedAuthor최, 경숙-
dc.type.localJournal Papers-
dc.citation.titleJournal of cellular biochemistry-
dc.identifier.bibliographicCitationJournal of cellular biochemistry, 109(5):885-895, 2010-
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
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