Oxidative Stress Causes Enhanced Secretion of YB-1 Protein that Restrains Proliferation of Receiving Cells
Open Access
- 22 October 2018
- Vol. 9 (10), 513
- https://doi.org/10.3390/genes9100513
Abstract
The prototype cold-shock Y-box binding protein 1 (YB-1) is a multifunctional protein that regulates a variety of fundamental biological processes including cell proliferation and migration, DNA damage, matrix protein synthesis and chemotaxis. The plethora of functions assigned to YB-1 is strictly dependent on its subcellular localization. In resting cells, YB-1 localizes to cytoplasm where it is a component of messenger ribonucleoprotein particles. Under stress conditions, YB-1 contributes to the formation of stress granules (SGs), cytoplasmic foci where untranslated messenger RNAs (mRNAs) are sorted or processed for reinitiation, degradation, or packaging into ribonucleoprotein particles (mRNPs). Following DNA damage, YB-1 translocates to the nucleus and participates in DNA repair thereby enhancing cell survival. Recent data show that YB-1 can also be secreted and YB-1-derived polypeptides are found in plasma of patients with sepsis and malignancies. Here we show that in response to oxidative insults, YB-1 assembly in SGs is associated with an enhancement of YB-1 protein secretion. An enriched fraction of extracellular YB-1 (exYB-1) significantly inhibited proliferation of receiving cells and such inhibition was associated to a G2/M cell cycle arrest, induction of p21WAF and reduction of ΔNp63α protein level. All together, these data show that acute oxidative stress causes sustained release of YB-1 as a paracrine/autocrine signal that stimulate cell cycle arrest.This publication has 55 references indexed in Scilit:
- Inflammatory cell infiltration and resolution of kidney inflammation is orchestrated by the cold-shock protein Y-box binding protein-1Kidney International, 2017
- Therapeutic nuclear shuttling of YB-1 reduces renal damage and fibrosisKidney International, 2016
- Does the Interdependence between Oxidative Stress and Inflammation Explain the Antioxidant Paradox?Oxidative Medicine and Cellular Longevity, 2016
- YB-1 regulates stress granule formation and tumor progression by translationally activating G3BP1The Journal of cell biology, 2015
- Ribonucleoprotein Y-box-binding protein-1 regulates mitochondrial oxidative phosphorylation (OXPHOS) protein expression after serum stimulation through binding to OXPHOS mRNABiochemical Journal, 2012
- Y-box-binding protein 1 (YB-1) and its functionsBiochemistry (Moscow), 2011
- A Novel Small Compound That Promotes Nuclear Translocation of YB-1 Ameliorates Experimental Hepatic Fibrosis in MiceOnline Journal of Public Health Informatics, 2011
- The pleiotropic functions of the Y‐box‐binding protein, YB‐1BioEssays, 2003
- Direct Involvement of the Y-box Binding Protein YB-1 in Genotoxic Stress-induced Activation of the Human Multidrug Resistance 1 GeneOnline Journal of Public Health Informatics, 1998
- Characterization of the cDNA encoding a protein binding to the major histocompatibility complex class II Y box.Proceedings of the National Academy of Sciences of the United States of America, 1988