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FOXO3a turns the tumor necrosis factor receptor signaling towards apoptosis through reciprocal regulation of c-Jun N-terminal kinase and NF-kappaB
DC Field | Value | Language |
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dc.contributor.author | Lee, Hae-Young | - |
dc.contributor.author | Youn, Seock-Won | - |
dc.contributor.author | Kim, Ju-Young | - |
dc.contributor.author | Park, Kyung-Woo | - |
dc.contributor.author | Hwang, Chang-Il | - |
dc.contributor.author | Park, Woong-Yang | - |
dc.contributor.author | Oh, Byung-Hee | - |
dc.contributor.author | Park, Young-Bae | - |
dc.contributor.author | Walsh, Kenneth | - |
dc.contributor.author | Seo, Jeong-Sun | - |
dc.contributor.author | Kim, Hyo-Soo | - |
dc.date.accessioned | 2010-06-07T01:35:23Z | - |
dc.date.available | 2010-06-07T01:35:23Z | - |
dc.date.issued | 2007-11-23 | - |
dc.identifier.citation | Arterioscler Thromb Vasc Biol. 2008;28(1):112-120 | en |
dc.identifier.issn | 1524-4636 (Electronic) | - |
dc.identifier.uri | http://atvb.ahajournals.org/cgi/reprint/28/1/112.pdf | - |
dc.identifier.uri | https://hdl.handle.net/10371/67494 | - |
dc.description.abstract | OBJECTIVE: We evaluated the full range effects of FOXO3a in endothelial cells (ECs) by microarray analysis and investigated the role of FOXO3a regulating TNF receptor signaling pathway. METHODS AND RESULTS: Human umbilical vein endothelial cells (HUVECs) were transfected with adenoviral vectors expressing constitutively active FOXO3a (Ad-TM-FOXO3a). Ad-TM-FOXO3a transfection caused remarkable apoptosis, which were accompanied with upregulation of genes related with TNF receptor signaling, such as TNF-alpha, TANK (TRAF-associated NF-kappaB activator), and TTRAP (TRAF and TNF receptor-associated protein). Furthermore, kappaB-Ras1 (IkappaB-interacting Ras-like protein-1) which is known to block IkappaB degradation was found increased, and intranuclear translocation of NF-kappaB was inhibited. GADD45beta and XIAP, negative regulators of c-Jun N-terminal kinase (JNK), were suppressed and JNK activity was increased. Attenuation of TNF signaling pathway either by blocking antibody for TNF receptor or by blocking JNK with DMAP (6-dimethylaminopurine) or Ad-TAM67 (dominant negative c-Jun) cotransfection, significantly reduced FOXO3a-induced apoptosis. Finally, treatment of vasculature with heat shock, an activator of endogenous FOXO3a, resulted in EC apoptosis, which was completely rescued by Ad-TAM67. CONCLUSIONS: FOXO3a promotes apoptosis of ECs, through activation of JNK and suppression of NF-kappaB. These data identify a novel role of FOXO3a to turn TNF receptor signaling to a proapoptotic JNK-dependent pathway. | en |
dc.language.iso | en | en |
dc.publisher | American Heart Association | en |
dc.subject | Adenoviridae/genetics | en |
dc.subject | Animals | en |
dc.subject | Apoptosis/*physiology | en |
dc.subject | Carotid Arteries/physiology | en |
dc.subject | Cells, Cultured | en |
dc.subject | Endothelial Cells/*metabolism | en |
dc.subject | Forkhead Transcription Factors/*physiology | en |
dc.subject | Genetic Vectors | en |
dc.subject | Humans | en |
dc.subject | JNK Mitogen-Activated Protein Kinases/*metabolism | en |
dc.subject | NF-kappa B p50 Subunit/*metabolism | en |
dc.subject | Oligonucleotide Array Sequence Analysis | en |
dc.subject | Rats | en |
dc.subject | Receptors, Tumor Necrosis Factor/*physiology | en |
dc.subject | Signal Transduction | en |
dc.subject | Transfection | en |
dc.subject | Tumor Necrosis Factor-alpha/*metabolism | en |
dc.subject | Umbilical Veins/cytology | en |
dc.subject | Up-Regulation | en |
dc.title | FOXO3a turns the tumor necrosis factor receptor signaling towards apoptosis through reciprocal regulation of c-Jun N-terminal kinase and NF-kappaB | en |
dc.type | Article | en |
dc.contributor.AlternativeAuthor | 이해영 | - |
dc.contributor.AlternativeAuthor | 윤석원 | - |
dc.contributor.AlternativeAuthor | 김주영 | - |
dc.contributor.AlternativeAuthor | 박경우 | - |
dc.contributor.AlternativeAuthor | 황창일 | - |
dc.contributor.AlternativeAuthor | 박웅양 | - |
dc.contributor.AlternativeAuthor | 오병희 | - |
dc.contributor.AlternativeAuthor | 박영배 | - |
dc.contributor.AlternativeAuthor | 서정선 | - |
dc.contributor.AlternativeAuthor | 김효수 | - |
dc.identifier.doi | 10.1161/ATVBAHA.107.153304 | - |
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