PERK up! Resveratrol-Induced Stress Granules Involve PERK Pathway Activation.Public
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Resveratrol (Rsv) is a polyphenol produced by plants in response to cell stress and causes the formation of stress granules (SGs) at high doses. The formation of SGs often but not always results in downstream activation of the integrated stress response (ISR) and phosphorylation of the translational regulator eIF2ɑ. Our research aimed to determine whether eIF2ɑ phosphorylation was required for Rsv-induced SGs, and if so which eIF2ɑ kinase (i.e., PERK, PKR, HRI, or GCN2) activates the ISR when exposed to Rsv. SG formation was visualized through fluorescence microscopy in human haploid cells (HAP1) with CRISPR-mediated deletions of each kinase, or mutation of the critical phosphorylation site of eIF2ɑ (Ser51Ala). The Ser51Ala cell line and the ΔPERK cell line did not efficiently form SGs in response to Rsv, suggesting that PERK-mediated phosphorylation of eIF2ɑ is required for Rsv SGs. However, a western blot showed phosphorylation of eIF2ɑ remained in ΔPERK cells after Rsv exposure. Both experiments indicate that while the PERK-mediated phosphorylation of eIF2ɑ may not be essential to SG formation in HAP1 cells exposed to Rsv, it is involved.
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