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YB-1 Mediates TNF-Induced Pro-Survival Signaling by Regulating NF-κB Activation.
Shah, Aneri Plaza-Sirvent, Carlos Weinert, Sönke Buchbinder, Jörn H Lavrik, Inna N Mertens, Peter R Schmitz, Ingo Lindquist, Jonathan A
Shah, Aneri
Plaza-Sirvent, Carlos
Weinert, Sönke
Buchbinder, Jörn H
Lavrik, Inna N
Mertens, Peter R
Schmitz, Ingo
Lindquist, Jonathan A
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2020-08-05
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Abstract
Cell fate decisions regulating survival and death are essential for maintaining tissue homeostasis; dysregulation thereof can lead to tumor development. In some cases, survival and death are triggered by the same receptor, e.g., tumor necrosis factor (TNF)-receptor 1 (TNFR1). We identified a prominent role for the cold shock Y-box binding protein-1 (YB-1) in the TNF-induced activation and nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65. In the absence of YB-1, the expression of TNF receptor-associated factor 2 (TRAF2), a central component of the TNF receptor signaling complex required for NF-κB activation, is significantly reduced. Therefore, we hypothesized that the loss of YB-1 results in a destabilization of TRAF2. Consistent with this hypothesis, we observed that YB-1-deficient cells were more prone to TNF-induced apoptotic cell death. We observed enhanced effector caspase-3 activation and could successfully rescue the cells using the pan-caspase inhibitor zVAD-fmk, but not necrostatin-1. Taken together, our results indicate that YB-1 plays a central role in promoting cell survival through NF-κB activation and identifies a novel mechanism by which enhanced YB-1 expression may contribute to tumor development.
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Cancers (Basel). 2020 Aug 5;12(8):2188. doi: 10.3390/cancers12082188.
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en
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2072-6694
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Attribution-NonCommercial-ShareAlike 4.0 International