Back to Search
Start Over
YB-1 Mediates TNF-Induced Pro-Survival Signaling by Regulating NF-κB Activation.
- Source :
-
Cancers [Cancers (Basel)] 2020 Aug 05; Vol. 12 (8). Date of Electronic Publication: 2020 Aug 05. - Publication Year :
- 2020
-
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.
Details
- Language :
- English
- ISSN :
- 2072-6694
- Volume :
- 12
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Cancers
- Publication Type :
- Academic Journal
- Accession number :
- 32764479
- Full Text :
- https://doi.org/10.3390/cancers12082188