Next Article in Journal
The Role of Necroptosis in ROS-Mediated Cancer Therapies and Its Promising Applications
Next Article in Special Issue
YB-1 Knockdown Inhibits the Proliferation of Mesothelioma Cells through Multiple Mechanisms
Previous Article in Journal
Phenotypic and Functional Characterization of NK Cells in αβT-Cell and B-Cell Depleted Haplo-HSCT to Cure Pediatric Patients with Acute Leukemia
Previous Article in Special Issue
Dephosphorylation of YB-1 is Required for Nuclear Localisation During G2 Phase of the Cell Cycle
Open AccessArticle

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
3
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
5
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
Show Figures

Graphical abstract

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.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop