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.
Highlights
Oxidative stress is linked to a number of chronic diseases including diabetes, neurodegenerative and cardiovascular diseases, cancer, and aging [1]
Y-box binding protein 1 (YB-1) Is Recruited in Stress Granules under Diverse Stress Stimuli
By double immunofluorescence labelling and confocal microscopy antibodies against YB-1 and PABP1, another specific stress granules (SGs) marker [43], we found that YB-1 and PABP1 using antibodies against YB-1 and PABP1, another specific SGs marker [43], we found that YB-1 and were evenly distributed in the cytoplasm in resting conditions (Figure 1a, control)
Summary
Oxidative stress is linked to a number of chronic diseases including diabetes, neurodegenerative and cardiovascular diseases, cancer, and aging [1]. The cold-shock Y-box binding protein 1 (YB-1) is involved in stress response [2] and chronic inflammation [3,4,5]. YB-1 is a member of the evolutionarily conserved cold shock domain (CSD) proteins and was first identified as a DNA binding protein interacting with the Y-box motif present in the major histocompatibility complex class II gene [6]. YB-1 protein is upregulated in many types of human cancers including, breast, prostate, ovarian and melanoma [12,13].
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