Cited 30 times in
Caspase-Mediated p65 Cleavage Promotes TRAIL-Induced Apoptosis
DC Field | Value | Language |
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dc.contributor.author | 장인익 | - |
dc.date.accessioned | 2015-08-26T16:43:57Z | - |
dc.date.available | 2015-08-26T16:43:57Z | - |
dc.date.issued | 2005 | - |
dc.identifier.issn | 0008-5472 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/114987 | - |
dc.description.abstract | Tumor 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.statementOfResponsibility | open | - |
dc.format.extent | 6111~6119 | - |
dc.relation.isPartOf | CANCER RESEARCH | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Apoptosis/drug effects* | - |
dc.subject.MESH | Apoptosis/physiology | - |
dc.subject.MESH | Apoptosis Regulatory Proteins | - |
dc.subject.MESH | Carcinoma, Hepatocellular/genetics | - |
dc.subject.MESH | Carcinoma, Hepatocellular/metabolism | - |
dc.subject.MESH | Carcinoma, Hepatocellular/pathology | - |
dc.subject.MESH | Caspase 3 | - |
dc.subject.MESH | Caspases/metabolism* | - |
dc.subject.MESH | Cell Line, Tumor | - |
dc.subject.MESH | Enzyme Activation/drug effects | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Liver Neoplasms/genetics | - |
dc.subject.MESH | Liver Neoplasms/metabolism | - |
dc.subject.MESH | Liver Neoplasms/pathology | - |
dc.subject.MESH | Membrane Glycoproteins/pharmacology* | - |
dc.subject.MESH | NF-kappa B/antagonists & inhibitors | - |
dc.subject.MESH | NF-kappa B/genetics | - |
dc.subject.MESH | NF-kappa B/metabolism* | - |
dc.subject.MESH | Proteins/metabolism | - |
dc.subject.MESH | TNF-Related Apoptosis-Inducing Ligand | - |
dc.subject.MESH | Transcription Factor RelA | - |
dc.subject.MESH | Transfection | - |
dc.subject.MESH | Tumor Necrosis Factor-alpha/pharmacology* | - |
dc.subject.MESH | X-Linked Inhibitor of Apoptosis Protein | - |
dc.title | Caspase-Mediated p65 Cleavage Promotes TRAIL-Induced Apoptosis | - |
dc.type | Article | - |
dc.contributor.college | College of Dentistry (치과대학) | - |
dc.contributor.department | Dept. of Oral Biology (구강생물학) | - |
dc.contributor.googleauthor | Hun Sik Kim | - |
dc.contributor.googleauthor | Inik Chang | - |
dc.contributor.googleauthor | Myung-Shik Lee | - |
dc.contributor.googleauthor | Kyung-Hee Choi | - |
dc.contributor.googleauthor | Ja Young Kim | - |
dc.identifier.doi | 10.1158/0008-5472.CAN-05-0472 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A03461 | - |
dc.relation.journalcode | J00452 | - |
dc.identifier.eissn | 1538-7445 | - |
dc.identifier.pmid | 16024612 | - |
dc.subject.keyword | 16024612 | - |
dc.contributor.alternativeName | Chang, In Ik | - |
dc.contributor.affiliatedAuthor | Chang, In Ik | - |
dc.rights.accessRights | free | - |
dc.citation.volume | 65 | - |
dc.citation.number | 14 | - |
dc.citation.startPage | 6111 | - |
dc.citation.endPage | 6119 | - |
dc.identifier.bibliographicCitation | CANCER RESEARCH, Vol.65(14) : 6111-6119, 2005 | - |
dc.identifier.rimsid | 39362 | - |
dc.type.rims | ART | - |
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