Proceedings of the National Academy of Sciences · 2020 · 19 citations · 31 references
Life SciencesCancer BiologyOncologyCell SignalingMolecular OncologySignal TransductionApoptosis ResistanceApoptotic SignalingInflammatory Cell SignalingInflammatory SignalingOncogenic Signaling PathwaysProtein Phosphatase SignalingCancer Cell Survival SignalingCellular Inflammatory ResponsesNf-kappa B-mediated Anti-apoptotic SignalingNf-κb SignalingNuclear Factor Kappa B ActivationNuclear Factor Kappa B ModulationNuclear Factor Kappa B SignalingTherapeutic Target Identification
Significance The NF-κB signaling pathway is critical for cellular responses to cell-extrinsic insults. Its dysregulation impacts cancer patients’ survival and response to available therapeutics. NF-κB utilizes the PPM1G phosphatase as a coactivator to induce inflammatory and cell survival programs in response to proinflammatory cytokines. However, how PPM1G activity is regulated to facilitate tunable control and insult resolution remains enigmatic. We take advantage of biochemical and genetic approaches and patient tumor data analysis to reveal a key function of the p14 ARF tumor suppressor in targeting PPM1G to negatively tune NF-κB transcriptional function, thereby controlling inflammatory and apoptotic responses. We propose that PPM1G emerges as a therapeutic target in a variety of cancers arising from ARF loss of function to oncogenic NF-κB activation.
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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
Suppression of TNF-α-Induced Apoptosis by NF-κB
Daniel J. Van Antwerp, Séamus J. Martin, Tal Kafri et al. · Science · 1996 · 2.6K citations