Bclaf1 regulates c‐FLIP expression and protects cells from TNF‐induced apoptosis and tissue injury. (25th October 2021)

• Record Type: Journal Article
• Authors: Zhang, Rui; Xue, Teng; Shao, Anwen; Lang, Yue; Qin, Chao; Zhao, Mingliang; Kuang, Yu; Yu, Zhengquan; Geng, Yunyun; Zhao, Chenyang; Tang, Jun
• Is Part Of: EMBO reports. Volume 23:Number 1(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-10-25
• Subjects: apoptosis -- Bclaf1 -- c‐FLIP -- TNF; Molecular biology -- Periodicals; Molecular Biology -- Periodicals; Molecular biology; Periodicals; 572.8
• DOI: 10.15252/embr.202152702
• Languages: English
• ISSNs: 1469-221X

Abstract

Abstract: TNF stimulation generates pro‐survival signals through activation of NF‐κB that restrict the build‐in death signaling triggered by TNF. The competition between TNF‐induced survival and death signals ultimately determines the fate of a cell. Here, we report the identification of Bclaf1 as a novel component of the anti‐apoptotic program of TNF. Bclaf1 depletion in multiple cells sensitizes cells to TNF‐induced apoptosis but not to necroptosis. Bclaf1 exerts its anti‐apoptotic function by promoting the transcription of CFLAR, a caspase 8 antagonist, downstream of NF‐κB activation. Bclaf1 binds to the p50 subunit of NF‐κB, which is required for Bclaf1 to stimulate CFLAR transcription. Finally, in Bclaf1 siRNA administered mice, TNF‐induced small intestine injury is much more severe than in control mice with aggravated signs of apoptosis and pyroptosis. These results suggest Bclaf1 is a key regulator in TNF‐induced apoptosis, both in vitro and in vivo . Synopsis: Bclaf1 functions in the anti‐apoptotic program of the TNF signaling pathway. Bclaf1 positively regulates c‐FLIP expression via p50 and protects cells from TNF‐induced apoptosis and tissue injury. Bclaf1 deficiency sensitizes cells to apoptosis in response to TNF and aggravates TNF‐induced damage of mouse intestinal epithelia. Bclaf1 inhibits TNF‐induced apoptosis by upregulating c‐FLIP. Bclaf1 interacts with p50 and positively regulates the transcription of CFLAR through p50. Abstract : Bclaf1 functions in the anti‐apoptotic program of the TNF signaling pathway. Bclaf1 positively regulates c‐FLIP expression via p50 and protects cells from TNF‐induced apoptosis and tissue injury.