PMID- 32764479 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200928 IS - 2072-6694 (Print) IS - 2072-6694 (Electronic) IS - 2072-6694 (Linking) VI - 12 IP - 8 DP - 2020 Aug 5 TI - YB-1 Mediates TNF-Induced Pro-Survival Signaling by Regulating NF-kappaB Activation. LID - 10.3390/cancers12082188 [doi] LID - 2188 AB - 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-kappaB) 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-kappaB 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-kappaB activation and identifies a novel mechanism by which enhanced YB-1 expression may contribute to tumor development. FAU - Shah, Aneri AU - Shah A AD - Clinic of Nephrology and Hypertension, Diabetes and Endocrinology, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany. FAU - Plaza-Sirvent, Carlos AU - Plaza-Sirvent C AD - Institute for Molecular and Clinical Immunology, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany. AD - Systems-Oriented Immunology and Inflammation Research Group, Department of Experimental Immunology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany. AD - Department of Molecular Immunology, ZKF2, Ruhr-University Bochum, D-44780 Bochum, Germany. FAU - Weinert, Sonke AU - Weinert S AUID- ORCID: 0000-0002-7201-0836 AD - Department of Cardiology and Angiology, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany. FAU - Buchbinder, Jorn H AU - Buchbinder JH AD - Translational Inflammation Research, Institute of Experimental Internal Medicine, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany. FAU - Lavrik, Inna N AU - Lavrik IN AD - Translational Inflammation Research, Institute of Experimental Internal Medicine, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany. FAU - Mertens, Peter R AU - Mertens PR AD - Clinic of Nephrology and Hypertension, Diabetes and Endocrinology, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany. FAU - Schmitz, Ingo AU - Schmitz I AUID- ORCID: 0000-0002-5360-0419 AD - Institute for Molecular and Clinical Immunology, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany. AD - Systems-Oriented Immunology and Inflammation Research Group, Department of Experimental Immunology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany. AD - Department of Molecular Immunology, ZKF2, Ruhr-University Bochum, D-44780 Bochum, Germany. FAU - Lindquist, Jonathan A AU - Lindquist JA AUID- ORCID: 0000-0001-6846-5056 AD - Clinic of Nephrology and Hypertension, Diabetes and Endocrinology, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany. LA - eng GR - Project-ID 97850925 - SFB 854: Project A1 to PRM and project A23 to IS, as well as GRK 2408, project 8, grants ME-1365/7-2 and ME-1365/9-2 to PRM, LA-2386/6-1 to IL, and LI-1031/4-1 to JAL/Deutsche Forschungsgemeinschaft/ GR - project number ZS/2016/08/80645/federal state Saxony-Anhalt and the European Structural and Investment Funds (ESF, 2014-2020)/ PT - Journal Article DEP - 20200805 PL - Switzerland TA - Cancers (Basel) JT - Cancers JID - 101526829 PMC - PMC7464034 OTO - NOTNLM OT - TNF OT - apoptosis OT - cold shock proteins COIS- The authors declare no conflict of interest. The funding agencies had no role in the study design; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish. EDAT- 2020/08/09 06:00 MHDA- 2020/08/09 06:01 PMCR- 2020/08/05 CRDT- 2020/08/09 06:00 PHST- 2020/06/23 00:00 [received] PHST- 2020/07/25 00:00 [revised] PHST- 2020/08/04 00:00 [accepted] PHST- 2020/08/09 06:00 [entrez] PHST- 2020/08/09 06:00 [pubmed] PHST- 2020/08/09 06:01 [medline] PHST- 2020/08/05 00:00 [pmc-release] AID - cancers12082188 [pii] AID - cancers-12-02188 [pii] AID - 10.3390/cancers12082188 [doi] PST - epublish SO - Cancers (Basel). 2020 Aug 5;12(8):2188. doi: 10.3390/cancers12082188.