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Article

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

1
Clinic of Nephrology and Hypertension, Diabetes and Endocrinology, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany
2
Institute for Molecular and Clinical Immunology, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany
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Systems-Oriented Immunology and Inflammation Research Group, Department of Experimental Immunology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany
4
Department of Molecular Immunology, ZKF2, Ruhr-University Bochum, D-44780 Bochum, Germany
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Department of Cardiology and Angiology, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany
6
Translational Inflammation Research, Institute of Experimental Internal Medicine, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany
*
Authors to whom correspondence should be addressed.
Cancers 2020, 12(8), 2188; https://doi.org/10.3390/cancers12082188
Received: 23 June 2020 / Revised: 25 July 2020 / Accepted: 4 August 2020 / Published: 5 August 2020
(This article belongs to the Special Issue Close links between Cold Shock Proteins and Cancer)
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. View Full-Text
Keywords: cold shock proteins; TNF; apoptosis cold shock proteins; TNF; apoptosis
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MDPI and ACS Style

Shah, A.; Plaza-Sirvent, C.; Weinert, S.; Buchbinder, J.H.; Lavrik, I.N.; Mertens, P.R.; Schmitz, I.; Lindquist, J.A. YB-1 Mediates TNF-Induced Pro-Survival Signaling by Regulating NF-κB Activation. Cancers 2020, 12, 2188. https://doi.org/10.3390/cancers12082188

AMA Style

Shah A, Plaza-Sirvent C, Weinert S, Buchbinder JH, Lavrik IN, Mertens PR, Schmitz I, Lindquist JA. YB-1 Mediates TNF-Induced Pro-Survival Signaling by Regulating NF-κB Activation. Cancers. 2020; 12(8):2188. https://doi.org/10.3390/cancers12082188

Chicago/Turabian Style

Shah, Aneri, Carlos Plaza-Sirvent, Sönke Weinert, Jörn H. Buchbinder, Inna N. Lavrik, Peter R. Mertens, Ingo Schmitz, and Jonathan A. Lindquist. 2020. "YB-1 Mediates TNF-Induced Pro-Survival Signaling by Regulating NF-κB Activation" Cancers 12, no. 8: 2188. https://doi.org/10.3390/cancers12082188

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