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YB-1 Mediates TNF-Induced Pro-Survival Signaling by Regulating NF-?B Activation.

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-?B) 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-?B 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-?B activation and identifies a novel mechanism by which enhanced YB-1 expression may contribute to tumor development.

SUBMITTER: Shah A

PROVIDER: S-EPMC7464034 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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YB-1 Mediates TNF-Induced Pro-Survival Signaling by Regulating NF-κB Activation.

Shah Aneri A Plaza-Sirvent Carlos C Weinert Sönke S Buchbinder Jörn H JH Lavrik Inna N IN Mertens Peter R PR Schmitz Ingo I Lindquist Jonathan A JA

Cancers 20200805 8

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 ...[more]

PMID: 32764479

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Dataset Information

YB-1 Mediates TNF-Induced Pro-Survival Signaling by Regulating NF-?B Activation.

Publications

YB-1 Mediates TNF-Induced Pro-Survival Signaling by Regulating NF-κB Activation.

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