Role of YB-1 and NF-κB in TNFR signaling pathways : deciding cell survival or death

Abstract

Y-box binding protein-1 (YB-1) belongs to the family of cold shock proteins that are characterized by an evolutionary and structurally conserved cold shock domain. The cold shock domain binds both RNA and single stranded DNA, therefore YB-1 has pleiotropic functions in cell proliferation, differentiation, stress response, DNA repair, and inflammation. Cell undergo stress in many ways, e.g., radiation, interferon release in response to viral infection, and lipopolysaccharide produced by bacteria. Binding of these factors to their receptors induces kinase activation, which phosphorylate YB-1. The same pathways also activate nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), a well-known transcription factor, which regulates genes involved in immune responses, cell proliferation, and inflammation or apoptosis. Life or death decisions within cells are critical for development as well as in the defence against infectious diseases and cancer formation. Apoptosis has long been considered the only form of programmed cell death occurring during development and disease progression. Now, in addition to apoptosis, necroptosis (a programmed form of necrosis) can also be initiated by activation of death receptors. Survival, apoptosis, and necroptosis are all triggered by the same cell surface receptors e.g., tumor necrosis factor receptor 1 (TNFR1). Our novel findings showed a prominent role of YB-1 in the TNF-induced activation and nuclear translocation of NF-κB p65. We are the first to show that depleting YB-1 tips the balance from survival to enhanced apoptosis in TNFR1 signaling pathway.