Genes & Development · 1999 · 727 citations · 35 references
Life SciencesCell BiologyMolecular BiologyApoptosisGene ExpressionSignal TransductionApoptosis In CancerApoptosis RegulationApoptosis ResistanceApoptotic Signal TransductionApoptotic SignalingBcl-2 Family ProteinsApoptosis Signaling In CancerApoptotic ResponseBfl-1 FunctionNf-kappa B-dependent TranscriptionNuclear Factor Kappa B ActivationNuclear Factor Kappa B InhibitionNuclear Factor Kappa B SignalingPromoter Activity Analysis
Bcl‑2 family proteins regulate apoptosis, and NF‑κB–driven expression of Bfl‑1 in immune tissues supports its protective role in immunity. Promoter analysis revealed an NF‑κB binding site that drives Bfl‑1 transcription. Bfl‑1/A1 is a direct NF‑κB target that, when induced, can replace NF‑κB to block TNFα‑induced apoptosis and may mediate NF‑κB’s oncogenic and chemoresistance effects.
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.
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An Essential Role for NF-κB in Preventing TNF-α-Induced Cell Death
Amer A. Beg, David Baltimore · Science · 1996 · 3.1K citations