Ask about this productRelated genes to: G3BP1 antibody
- Gene:
- G3BP1 NIH gene
- Name:
- G3BP stress granule assembly factor 1
- Previous symbol:
- -
- Synonyms:
- HDH-VIII, G3BP
- Chromosome:
- 5q33.1
- Locus Type:
- gene with protein product
- Date approved:
- 2006-10-25
- Date modifiied:
- 2016-02-29
Related products to: G3BP1 antibody
Related articles to: G3BP1 antibody
- Biomolecular condensates are a major driver of cellular organization; however, we lack a predictable and systematic approach to modulate the multivalent interactions underlying their formation. Here, we demonstrate that the AI-driven FragFold method enables robust and generalizable design of protein fragments to control biomolecular condensate formation. We apply this approach across diverse proteins: G3BP1, SARS-CoV-2 nucleocapsid, TDP-43, and focal adhesion kinase (FAK). Computationally screening 2,235 fragments, we selected 18 candidates for further investigation. Overall, we attain a 50% success rate (9/18 designs) in discovering condensate-controlling protein fragments, experimentally testing just 3-5 candidates per protein. For each condensate-forming protein, the success rate is at least 40%. Furthermore, FragFold-predicted fragment binding modes align with their condensate-inhibitory or -enhancing activities, revealing both known and newly identified interactions underlying condensate formation. In FAK, a condensate-inhibitory fragment uncovered a domain interaction required for phase separation, and mutational analysis validated its importance. Notably, this inhibitory fragment also suppresses FAK condensate formation in living mammalian cells. Together, these results establish AI-guided protein fragment discovery as a generalizable strategy to dissect and control the molecular interactions that govern biomolecular condensates. - Source: PubMed
Publication date: 2026/05/12
Savinov AndrewSadasivan JibinWhite Kyle JRubien Jack DLi Gene-WeiCase Lindsay B - Antisense oligonucleotides (ASOs) enter cells efficiently, but the compartment from which productive escape occurs remains uncertain. We used live-cell microscopy, ratiometric pH measurements and 3D focused ion beam scanning electron microscopy (FIB-SEM) in U2OS cells to track a -targeting ASO from uptake to delivery. The ASO entered by endocytosis and accumulated in late endosomes, endolysosomes and lysosomes, where it induced luminal neutralization without galectin-3 recruitment or limiting-membrane rupture. Under conditions that reduced -RNA by >90%, quantitative imaging showed that less than 4% of internalized ASOs reached the nucleus. L-leucyl-L-leucine methyl ester (LLOMe)-induced membrane damage released co-internalized dextran but not ASOs, showing that ASOs remain sequestered even in damaged late endocytic compartments. In apilimod-expanded organelles, ASOs concentrated at limiting membranes and intraluminal foci with constrained motion, consistent with association with membrane and luminal structures. Although G3BP1/2 has been proposed to plug damaged endocytic membranes, we detected no recruitment of G3BP1 to endosomes or lysosomes; loss of G3BP1 and G3BP2 increased functional delivery modestly. We therefore propose that productive escape occurs earlier in endocytosis, most likely in early or recycling endosomes, where ASOs would still be unbound within the lumen and where membrane fusion and fission could generate perforations permitting release. - Source: PubMed
Publication date: 2026/05/13
Sitarska EwaSaminathan AnandScanavachi GustavoSomerville ElliottCourtney Margo FReid Dylan ADanielsen Mathias BogetoftDavidsen Fie Kristine NoergaardJensen Knud JBennett C FrankKirchhausen Tom - Cytoplasmic mislocalization and aggregation of transactive response DNA-binding protein-43 (TDP-43) is a common pathological feature of amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration, and Alzheimer's disease with TDP-43 pathology (AD-TDP); the exact role of protein disulfide isomerase (PDI), an enzyme with chaperone activity, in modulating the pathological behavior of TDP-43 is unknown. In this study, we report that wild-type PDI, through its specific interaction with TDP-43, markedly attenuates phase separation of TDP-43, competitively displaces G3BP1 to disassemble TDP-43/G3BP1 condensates, and further counteracts the pathological mislocalization, abnormal phosphorylation, and pathological aggregation of TDP-43 through the b' domain of the enzyme. Ultimately, this alleviates mitochondrial damage and neuronal toxicity caused by TDP-43 aggregation and suppresses UNC13A cryptic splicing in stressed cells. In the presence of abnormal forms of PDI, however, PDI loses its activity, and stress granules containing TDP-43 are assembled into amyloid fibrils, resulting in mitochondrial impairment and neuronal cell death in ALS and AD-TDP patients. These findings not only provide new insights into the pathogenic mechanisms of TDP-43 in neurodegenerative diseases such as ALS and AD-TDP, but also propose PDI as a potential therapeutic target. - Source: PubMed
Publication date: 2026/05/25
Liu Jia-QiLiu HaoSun Yu-XuanLi YuyingLiu XiangyiWang Li-QiangYang ZhaofeiFu QiXu XiaojiaoChen JieZhang YingshuangZhou JunLe WeidongCui MengchaoLiang Yi - Glioblastoma stem cells (GSCs) are refractory to first-line treatment in the clinic, which includes irradiation (IR) and temozolomide (TMZ). Here we find that disrupting stress granules (SGs) sensitizes GSCs to IR/TMZ through ferroptosis. The profiling of SG proteins reveals the recruitment of iron-related proteins including ferritin. Mechanistically, G3BP1, an SG core protein, directly interacts with ferritin light chain in an IR/TMZ-induced G3BP1 methionine-333 oxidation-dependent manner. This interaction facilitates recruiting and sequestering ferritin into SGs, thereby restricting ferroptosis by limiting Fe content in the labile iron pool and preventing ferritinophagy. Disrupting G3BP1 and ferritin light chain binding using a screened small molecule, ciwujianoside C3, mitigates the restriction of SGs on ferroptosis, and resensitizes GSCs to IR/TMZ in both in vitro and animal models. These findings unveil a negative regulation of SGs on ferroptosis, and reveal a promising strategy to disrupt the SG-ferroptosis axis for treating glioblastomas and probably other types of cancer. - Source: PubMed
Publication date: 2026/05/22
Ge ZeheWang ZihanZhao ErjieGuo YizhuoZhang LongxiuTian FuweiLi MengdieMa YunfeiDing FangshuHe LiuguijieSun ShuhongTong MinfengXu WenxiaWang XiefengZhang JunxiaWu LingxiangZhang YudanNiu LiliWang QianghuYin RongLi XiaoYou YongpingRich Jeremy NWang XiuxingYao BingShi ZhumeiYang ZhouGe XinLiu FangChu BoQian Xu - It has long been recognized that the intracellular replication of alphaviruses critically relies on several key host RNA-binding proteins (RBPs), including G3BP1/2 and FXR1/FXR2/FMR1. But how these RBPs modulate alphaviral replication, and whether it would be possible to target them for antiviral treatment, is less explored. Here, using Semliki Forest virus (SFV) as a model, we report that SFV non-structural protein 3 (nsP3) exploits G3BP to drive its condensation and transforms antiviral stress granules into proviral nsP3-G3BP co-condensates. The gel-like co-condensates enrich and protect viral genomic RNAs from host RNase degradation and promote viral translation and replication. nsP3-RBP co-condensation is widespread among alphaviruses, and condensate disruption is a plausible antiviral approach. Thus, these findings uncover a general anti-alphavirus strategy based on the conserved reliance of virus-host protein co-condensation. - Source: PubMed
Publication date: 2026/05/21
Liu YiYao ZhiyingZhang YunZhu ZhenshuoWang ZiqiuChen QiYang ZeminHe YexuanChen XiaoxinTian LeDu JiangWu JinjunKim Hong JooHuang JingZhang YongdengMa WeiruiFan WenchunTaylor J PaulYang Peiguo