The prosurvival Bcl-2 homolog Bfl-1/A1 is a direct transcriptional target of NF-kappaB that blocks TNFalpha-induced apoptosis.
Bcl-2-family proteins are key regulators of the apoptotic response. Here, we demonstrate that the pro-survival Bcl-2 homolog Bfl-1/A1 is a direct transcriptional target of NF-kappaB. We show that bfl-1 gene expression is dependent on NF-kappaB activity and that it can substitute for NF-kappaB to suppress TNFalpha-induced apoptosis. bfl-1 promoter analysis identified an NF-kappaB site responsible for its Rel/NF-kappaB-dependent induction. The expression of bfl-1 in immune tissues supports the protective role of NF-kappaB in the immune system. The activation of Bfl-1 may be the means by which NF-kappaB functions in oncogenesis and promotes cell resistance to anti-cancer therapy.
Center for Advanced Biotechnology and Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Jersey 08854-5638 USA.
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WX
Zong
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LC
Edelstein
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Chen
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Bash
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Gélinas
D017209:Apoptosis / Q000235:genetics*; D002460:Cell Line; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D015778:Minor Histocompatibility Antigens; D016328:NF-kappa B / Q000235:genetics* / Q000276:immunology; D011401:Promoter Regions, Genetic / Q000235:genetics; D011506:Proteins / Q000235:genetics* / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D020569:Proto-Oncogene Proteins c-rel; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
C096816:BCL2-related protein A1; D015778:Minor Histocompatibility Antigens; D016328:NF-kappa B; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D020569:Proto-Oncogene Proteins c-rel; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha