Resveratrol and related stilbene derivatives induce stress granules with distinct clearance kinetics

Abstract

Stress Granules are ribonucleoprotein functional condensates that form during stress conditions in all eukaryotic cells. Although their stress-survival function is far from clear, Stress Granules have been implicated in the regulation of many vital cellular pathways. Consequently, SG dysfunction is thought to be a mechanistic point of origin for many neurodegenerative disorders, including Amyotrophic Lateral Sclerosis (ALS). Additionally, SGs are thought to play a role in pathogenic pathways as diverse as viral infection and chemotherapy resistance. There is a growing consensus around the hypothesis that understanding the mechanistic regulation of SG physical properties is essential to understanding their function. Although the internal dynamics and condensation mechanisms of SGs have been broadly investigated, there have been fewer investigations into the timing of SG formation and clearance in live cells. Since the lifetime of SG persistence can be a key factor in their function and tendency towards pathological dysregulation, SG clearance mechanisms deserve particular attention. Here we show that resveratrol and its analogues, piceatannol, pterostilbene, and 3,4,5,4′ tetramethoxystilbene induce G3BP-dependent SG formation with atypically rapid clearance kinetics. Resveratrol binds to G3BP, thereby reducing its protein-protein association valency. We suggest that altering G3BP valency is a pathway for the formation of uniquely transient SGs.

RNA Sequencing of Arabidopsis thaliana Seedlings after Non-Thermal Plasma-Seed Treatment Reveals Upregulation in Plant Stress and Defense Pathways

“…Moreover, it is common practice to use young seedlings because they are more sensitive to stress, and therefore, it would be possible to observe acute stress. A limitedtreatment time was chosen to avoid additional stresses such as heat stress, which induces a plethora of cellular effects [ 35 , 36 , 37 , 38 ]. Early germination was the macroscopic parameter used as an indicator of changes in the molecular biology, as shown in Figure 1 , which is an effect observed in other studies [ 39 ].…”

Tryptophan mutations in G3BP1 tune the stability of a cellular signaling hub by weakening transient interactions with Caprin1 and USP10

“…Currently, there are two published G3BP1 targeted peptide therapies including GAP161 ( 22 ), which blocks RasGAP association, and GAP159 ( 66 ), which inhibits G3BP1 expression. Resveratrol, an anticancer agent, has been shown to bind the G3BP1 NTF2-like domain and induce apoptosis via p53 activation ( 31 , 67 ). While these therapies are targeted toward cancer progression and metastasis, they do support the concept of targeting G3BP1 and its complex formation as advantageous and novel drug targets.…”

Stereochemistry of transient protein-protein interactions in a signaling hub: exploring G3BP1-mediated regulation of CFTR deubiquitination

“…Resveratrol, an anticancer agent, has been shown to bind the G3BP1 NTF2-like domain and induce apoptosis via p53 activation (31,63). While these therapies are targeted towards cancer progression and metastasis, they do support the concept of targeting G3BP1 and its complex formation as advantageous and novel drug targets.…”

“…Currently, there are two published G3BP1 targeted peptide therapies including GAP161 (22), which blocks RasGAP association, and GAP159 (62), which inhibits G3BP1 expression. Resveratrol, an anticancer agent, has been shown to bind the G3BP1 NTF2-like domain and induce apoptosis via p53 activation (31, 63). While these therapies are targeted towards cancer progression and metastasis, they do support the concept of targeting G3BP1 and its complex formation as advantageous and novel drug targets.…”