AF1q enhancement of gamma irradiation-induced apoptosis by up-regulation of BAD expression via NF-kappaB in human squamous carcinoma A431 cells
BAD (BCL-2 antagonist of cell death) is a pro-apoptotic BCL-2 family protein that plays a critical role in the regulation of apoptotic response. This study presents direct evidence that AF1q increased the radiation-induced apoptosis through up-regulation of BAD in human squamous carcinoma A431 cells...
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Veröffentlicht in: | Oncology reports 2010-08, Vol.24 (2), p.547-554 |
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description | BAD (BCL-2 antagonist of cell death) is a pro-apoptotic BCL-2 family protein that plays a critical role in the regulation of apoptotic response. This study presents direct evidence that AF1q increased the radiation-induced apoptosis through up-regulation of BAD in human squamous carcinoma A431 cells and the key transcription factor involved is NF-kappaB. The minimal promoter sequence of BAD was identified; the activity was increased in AF1q stable transfectants and decreased upon AF1q siRNA transfection. The NF-kappaB consensus binding sequence is detected on BAD promoter. Inactivation of NF-kappaB by NF-kappaB inhibitor Bay 11-7082 or NF-kappaB p65 siRNA suppressed the expression and promoter activity of BAD; the suppression is more obvious in AF1q stable transfectants which also have an elevated NF-kappaB level. Mutation of putative NF-kappaB motif decreased the BAD promoter activity. The binding of NF-kappaB to the BAD promoter was confirmed by chromatin-immunoprecipitation. These findings indicate that AF1q up-regulation of BAD is through its effect on NF-kappaB and this may hint of its oncogenic mechanism in cancer. |
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This study presents direct evidence that AF1q increased the radiation-induced apoptosis through up-regulation of BAD in human squamous carcinoma A431 cells and the key transcription factor involved is NF-kappaB. The minimal promoter sequence of BAD was identified; the activity was increased in AF1q stable transfectants and decreased upon AF1q siRNA transfection. The NF-kappaB consensus binding sequence is detected on BAD promoter. Inactivation of NF-kappaB by NF-kappaB inhibitor Bay 11-7082 or NF-kappaB p65 siRNA suppressed the expression and promoter activity of BAD; the suppression is more obvious in AF1q stable transfectants which also have an elevated NF-kappaB level. Mutation of putative NF-kappaB motif decreased the BAD promoter activity. The binding of NF-kappaB to the BAD promoter was confirmed by chromatin-immunoprecipitation. These findings indicate that AF1q up-regulation of BAD is through its effect on NF-kappaB and this may hint of its oncogenic mechanism in cancer.</description><identifier>EISSN: 1791-2431</identifier><identifier>PMID: 20596645</identifier><language>eng</language><publisher>Greece</publisher><subject>Apoptosis - drug effects ; Apoptosis - genetics ; Apoptosis - radiation effects ; Base Sequence ; bcl-Associated Death Protein - genetics ; bcl-Associated Death Protein - metabolism ; Blood Proteins - antagonists & inhibitors ; Blood Proteins - genetics ; Blood Proteins - physiology ; Carcinoma, Squamous Cell - genetics ; Carcinoma, Squamous Cell - metabolism ; Carcinoma, Squamous Cell - pathology ; Cell Line, Tumor ; Gamma Rays ; Gene Expression Regulation, Neoplastic - drug effects ; Gene Expression Regulation, Neoplastic - radiation effects ; Humans ; Molecular Sequence Data ; Neoplasm Proteins - antagonists & inhibitors ; Neoplasm Proteins - genetics ; Neoplasm Proteins - physiology ; NF-kappa B - antagonists & inhibitors ; NF-kappa B - genetics ; NF-kappa B - metabolism ; NF-kappa B - physiology ; Promoter Regions, Genetic ; Protein Binding ; Proto-Oncogene Proteins ; RNA, Small Interfering - pharmacology ; Transcription, Genetic - drug effects ; Transcription, Genetic - genetics ; Up-Regulation - drug effects ; Up-Regulation - genetics</subject><ispartof>Oncology reports, 2010-08, Vol.24 (2), p.547-554</ispartof><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20596645$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Co, Ngai Na</creatorcontrib><creatorcontrib>Tsang, Wing Pui</creatorcontrib><creatorcontrib>Tsang, Tsun Yee</creatorcontrib><creatorcontrib>Yeung, Chi Lam Au</creatorcontrib><creatorcontrib>Yau, Pak Lun</creatorcontrib><creatorcontrib>Kong, Siu Kai</creatorcontrib><creatorcontrib>Kwok, Tim Tak</creatorcontrib><title>AF1q enhancement of gamma irradiation-induced apoptosis by up-regulation of BAD expression via NF-kappaB in human squamous carcinoma A431 cells</title><title>Oncology reports</title><addtitle>Oncol Rep</addtitle><description>BAD (BCL-2 antagonist of cell death) is a pro-apoptotic BCL-2 family protein that plays a critical role in the regulation of apoptotic response. This study presents direct evidence that AF1q increased the radiation-induced apoptosis through up-regulation of BAD in human squamous carcinoma A431 cells and the key transcription factor involved is NF-kappaB. The minimal promoter sequence of BAD was identified; the activity was increased in AF1q stable transfectants and decreased upon AF1q siRNA transfection. The NF-kappaB consensus binding sequence is detected on BAD promoter. Inactivation of NF-kappaB by NF-kappaB inhibitor Bay 11-7082 or NF-kappaB p65 siRNA suppressed the expression and promoter activity of BAD; the suppression is more obvious in AF1q stable transfectants which also have an elevated NF-kappaB level. Mutation of putative NF-kappaB motif decreased the BAD promoter activity. The binding of NF-kappaB to the BAD promoter was confirmed by chromatin-immunoprecipitation. These findings indicate that AF1q up-regulation of BAD is through its effect on NF-kappaB and this may hint of its oncogenic mechanism in cancer.</description><subject>Apoptosis - drug effects</subject><subject>Apoptosis - genetics</subject><subject>Apoptosis - radiation effects</subject><subject>Base Sequence</subject><subject>bcl-Associated Death Protein - genetics</subject><subject>bcl-Associated Death Protein - metabolism</subject><subject>Blood Proteins - antagonists & inhibitors</subject><subject>Blood Proteins - genetics</subject><subject>Blood Proteins - physiology</subject><subject>Carcinoma, Squamous Cell - genetics</subject><subject>Carcinoma, Squamous Cell - metabolism</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Cell Line, Tumor</subject><subject>Gamma Rays</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Gene Expression Regulation, Neoplastic - radiation effects</subject><subject>Humans</subject><subject>Molecular Sequence Data</subject><subject>Neoplasm Proteins - antagonists & inhibitors</subject><subject>Neoplasm Proteins - genetics</subject><subject>Neoplasm Proteins - physiology</subject><subject>NF-kappa B - antagonists & inhibitors</subject><subject>NF-kappa B - genetics</subject><subject>NF-kappa B - metabolism</subject><subject>NF-kappa B - physiology</subject><subject>Promoter Regions, Genetic</subject><subject>Protein Binding</subject><subject>Proto-Oncogene Proteins</subject><subject>RNA, Small Interfering - pharmacology</subject><subject>Transcription, Genetic - drug effects</subject><subject>Transcription, Genetic - genetics</subject><subject>Up-Regulation - drug effects</subject><subject>Up-Regulation - genetics</subject><issn>1791-2431</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1kMFOwzAMhiskxMbgFVBunCo1TZM0x24wQJrgsnvlpu4WaNKsaRF7Cl6ZDsbJkv3Z_vRfRHMqFY3TjNFZdB3Ce5KkMhHqKpqlCVdCZHwefRdreiDo9uA0WnQD6RqyA2uBmL6H2sBgOhcbV48aawK-80MXTCDVkYw-7nE3tr_IaW9ZPBD88j2GcOp8GiCv6_gDvIclMY7sRwuOhMMIthsD0dBr47rpVTE5Eo1tG26iywbagLfnuoi268ft6jnevD29rIpN7DnnsUBZI-aV5CxhieK6EmlKuciV4EpnGjSVFKdRAxnFulI5y7IEVUIZNHnF2SK6_zvr--4wYhhKa8JJABxOaqVkTKR5LuVE3p3JsbJYl743Fvpj-R8h-wGNPmzC</recordid><startdate>201008</startdate><enddate>201008</enddate><creator>Co, Ngai Na</creator><creator>Tsang, Wing Pui</creator><creator>Tsang, Tsun Yee</creator><creator>Yeung, Chi Lam Au</creator><creator>Yau, Pak Lun</creator><creator>Kong, Siu Kai</creator><creator>Kwok, Tim Tak</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>201008</creationdate><title>AF1q enhancement of gamma irradiation-induced apoptosis by up-regulation of BAD expression via NF-kappaB in human squamous carcinoma A431 cells</title><author>Co, Ngai Na ; 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This study presents direct evidence that AF1q increased the radiation-induced apoptosis through up-regulation of BAD in human squamous carcinoma A431 cells and the key transcription factor involved is NF-kappaB. The minimal promoter sequence of BAD was identified; the activity was increased in AF1q stable transfectants and decreased upon AF1q siRNA transfection. The NF-kappaB consensus binding sequence is detected on BAD promoter. Inactivation of NF-kappaB by NF-kappaB inhibitor Bay 11-7082 or NF-kappaB p65 siRNA suppressed the expression and promoter activity of BAD; the suppression is more obvious in AF1q stable transfectants which also have an elevated NF-kappaB level. Mutation of putative NF-kappaB motif decreased the BAD promoter activity. The binding of NF-kappaB to the BAD promoter was confirmed by chromatin-immunoprecipitation. These findings indicate that AF1q up-regulation of BAD is through its effect on NF-kappaB and this may hint of its oncogenic mechanism in cancer.</abstract><cop>Greece</cop><pmid>20596645</pmid><tpages>8</tpages></addata></record> |
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subjects | Apoptosis - drug effects Apoptosis - genetics Apoptosis - radiation effects Base Sequence bcl-Associated Death Protein - genetics bcl-Associated Death Protein - metabolism Blood Proteins - antagonists & inhibitors Blood Proteins - genetics Blood Proteins - physiology Carcinoma, Squamous Cell - genetics Carcinoma, Squamous Cell - metabolism Carcinoma, Squamous Cell - pathology Cell Line, Tumor Gamma Rays Gene Expression Regulation, Neoplastic - drug effects Gene Expression Regulation, Neoplastic - radiation effects Humans Molecular Sequence Data Neoplasm Proteins - antagonists & inhibitors Neoplasm Proteins - genetics Neoplasm Proteins - physiology NF-kappa B - antagonists & inhibitors NF-kappa B - genetics NF-kappa B - metabolism NF-kappa B - physiology Promoter Regions, Genetic Protein Binding Proto-Oncogene Proteins RNA, Small Interfering - pharmacology Transcription, Genetic - drug effects Transcription, Genetic - genetics Up-Regulation - drug effects Up-Regulation - genetics |
title | AF1q enhancement of gamma irradiation-induced apoptosis by up-regulation of BAD expression via NF-kappaB in human squamous carcinoma A431 cells |
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