Bclaf1 is an important NF-κB signaling transducer and C/EBPβ regulator in DNA damage-induced senescence

Cell Death and Differentiation
A-w ShaoJ Tang

Abstract

Inducing senescence in cancer cells is an effective approach to suppress cancer growth, and it contributes significantly to the efficacy of therapeutic drugs. Previous studies indicated that transcription factors NF-κB (nuclear factor κ-light-chain-enhancer of activated B cells) and C/EBPβ (CCAAT/enhancer-binding protein-β) play a critical role in the establishment of senescence by upregulating proinflammatory cytokines, notably interleukin-6 (IL-6) and interleukin-8 (IL-8). However, it is not clear how these two factors are activated in response to senescence-inducing stimuli and subsequently regulate gene transcription. Here, we reveal Bcl-2-associated transcription factor 1 (Bclaf1) as a novel player in the therapeutic drug doxorubicin-induced senescence (TIS) in multiple cancer cells. Bclaf1 is upregulated through the ATM/Nemo/NF-κB pathway during TIS and is a direct target of p65 and c-Rel. The induction of Bclaf1 by NF-κB is essential for C/EBPβ upregulation and IL-6/IL-8 transcription during TIS. Bclaf1 can interact with the leucine zipper region of C/EBPβ and cooperate with C/EBPβ to upregulate IL-8. Furthermore, we show that Bclaf1 is required for the effectiveness of doxorubicin (Dox) treatment-induced tumor suppressi...Continue Reading

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Citations

Mar 28, 2017·Journal of Internal Medicine·M TesauroN Di Daniele
Feb 13, 2018·The Journal of Cell Biology·Xiang WangHongquan Zhang
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Jun 25, 2021·Molecular Systems Biology·Konstantinos SofiadisArgyris Papantonis
Apr 21, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Xian ChengLi Zhang

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