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Caspase-Mediated p65 Cleavage Promotes TRAIL-Induced Apoptosis

DC FieldValueLanguage
dc.contributor.author장인익-
dc.date.accessioned2015-08-26T16:43:57Z-
dc.date.available2015-08-26T16:43:57Z-
dc.date.issued2005-
dc.identifier.issn0008-5472-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/114987-
dc.description.abstractTumor necrosis factor (TNF)–related apoptosis-inducing ligand (TRAIL) is cytotoxic to a wide variety of transformed cells, but not to most normal cells, implying potential therapeutic value against advanced cancer. However, signal transduction in TRAIL-mediated apoptosis is not clearly understood compared with other TNF family members. Specifically, it is not yet understood how TRAIL controls nuclear factor κB (NF-κB) activation and overcomes its antiapoptotic effect. We explored the regulation of NF-κB activity by TRAIL and its role in apoptosis. TRAIL combined with IκBα-“superrepressor” induced potent apoptosis of SK-Hep1 hepatoma cells at low concentrations of TRAIL that do not independently induce apoptosis. Apoptosis by high concentrations of TRAIL was not affected by IκBα-superrepressor. Although TRAIL alone did not induce NF-κB activity, TRAIL combined with z-VAD significantly increased NF-κB activation. Analysis of the NF-κB activation pathway indicated that TRAIL unexpectedly induced cleavage of p65 at Asp97, which was blocked by z-VAD, accounting for all of these findings. p65 expression abrogated apoptosis and increased NF-κB activity in TRAIL-treated cells. Cleavage-resistant p65D97A further increased NF-κB activity in TRAIL-treated cells, whereas the COOH-terminal p65 fragment acted as a dominant-negative inhibitor. XIAP levels were increased by TRAIL in combination with z-VAD, whereas XIAP levels were decreased by TRAIL alone. Cleavage of p65 was also detected after FRO thyroid cancer cells were treated with TRAIL. These results suggest that TRAIL induces NF-κB activation, but simultaneously abrogates NF-κB activation by cleaving p65, and thereby inhibits the induction of antiapoptotic proteins such as XIAP, which contributes to the strong apoptotic activity of TRAIL compared with other TNF family members.-
dc.description.statementOfResponsibilityopen-
dc.format.extent6111~6119-
dc.relation.isPartOfCancer Research-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHApoptosis/drug effects*-
dc.subject.MESHApoptosis/physiology-
dc.subject.MESHApoptosis Regulatory Proteins-
dc.subject.MESHCarcinoma, Hepatocellular/genetics-
dc.subject.MESHCarcinoma, Hepatocellular/metabolism-
dc.subject.MESHCarcinoma, Hepatocellular/pathology-
dc.subject.MESHCaspase 3-
dc.subject.MESHCaspases/metabolism*-
dc.subject.MESHCell Line, Tumor-
dc.subject.MESHEnzyme Activation/drug effects-
dc.subject.MESHHumans-
dc.subject.MESHLiver Neoplasms/genetics-
dc.subject.MESHLiver Neoplasms/metabolism-
dc.subject.MESHLiver Neoplasms/pathology-
dc.subject.MESHMembrane Glycoproteins/pharmacology*-
dc.subject.MESHNF-kappa B/antagonists & inhibitors-
dc.subject.MESHNF-kappa B/genetics-
dc.subject.MESHNF-kappa B/metabolism*-
dc.subject.MESHProteins/metabolism-
dc.subject.MESHTNF-Related Apoptosis-Inducing Ligand-
dc.subject.MESHTranscription Factor RelA-
dc.subject.MESHTransfection-
dc.subject.MESHTumor Necrosis Factor-alpha/pharmacology*-
dc.subject.MESHX-Linked Inhibitor of Apoptosis Protein-
dc.titleCaspase-Mediated p65 Cleavage Promotes TRAIL-Induced Apoptosis-
dc.typeArticle-
dc.contributor.collegeCollege of Dentistry (치과대학)-
dc.contributor.departmentDept. of Oral Biology (구강생물학)-
dc.contributor.googleauthorHun Sik Kim-
dc.contributor.googleauthorInik Chang-
dc.contributor.googleauthorMyung-Shik Lee-
dc.contributor.googleauthorKyung-Hee Choi-
dc.contributor.googleauthorJa Young Kim-
dc.identifier.doi10.1158/0008-5472.CAN-05-0472-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA03461-
dc.relation.journalcodeJ00452-
dc.identifier.pmid16024612-
dc.subject.keyword16024612-
dc.contributor.alternativeNameChang, In Ik-
dc.contributor.affiliatedAuthorChang, In Ik-
dc.rights.accessRightsfree-
dc.citation.volume65-
dc.citation.number14-
dc.citation.startPage6111-
dc.citation.endPage6119-
dc.identifier.bibliographicCitationCancer Research, Vol.65(14) : 6111-6119, 2005-
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers

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