G3BP1 (G3BP Stress Granule Assembly Factor 1)

Furthermore, we explored a novel combination therapy involving the histone methyltransferase inhibitor MI-503 and enzalutamide in AR-positive and AR splice variant-positive cell lines. Our results confirmed the synergistic therapeutic effects of this combination, which can continue to inhibit the AR signaling pathway during the CRPC stage, thereby delaying disease progression. Taken together, our findings elucidate a critical KMT2D/G3BP1/SPOP/AR regulatory axis in prostate cancer progression and propose that targeted inhibition of histone methylation in combination with anti-androgen therapy represents a promising strategy for the management of advanced prostate cancer.

FHL1, TMPO, SERPINE1, and CRYAB are potential prognostic markers in GC. CRYAB may facilitate GC progression by regulating G3BP1-mediated SG assembly.

We map NSG microenvironments (temperature, polarity, pH, and proteasome activity), uncover dual disassembly-a slow VCP/19S-dependent route and a rapid SUMO/20S-dependent backup-and show that NSGs remodel chemo-plasticity: they mitigate doxorubicin/cisplatin toxicity in normal tissues yet sensitize tumors to nocodazole in vivo. Local induction and selective dissolution of NSGs thus offers a strategy to decouple efficacy from toxicity. Our results establish design rules linking nanomaterial surface chemistry to condensate programming and provide actionable levers to steer therapeutic outcomes.

In addition, PSMD11 could promote the progression of OSI-resistant LUAD by activating the NF-κB/IL-6/STAT3 signaling pathway. This signature has a high predictive effect on the prognosis of OSI-resistant LUAD patients, and can be used as a powerful predictive tool for further selection of chemotherapy and immunotherapy in OSI-resistant LUAD patients.

PARP10 knockdown reduces eIF2α phosphorylation and alters the SG core composition, notably decreasing translation factor presence. Based on our findings, we propose a model in which ADP-ribosylation acts as a rate-limiting step, initiating the formation of SGs.

Pathogenic VCP mutations that disrupt ASPL binding impair SG disassembly, a defect rescued by phosphomimetic mutations or ASPL depletion. Our findings suggest that disruptions in the ASPL-VCP interaction uncouple SG assembly and disassembly, representing a potential mechanism underlying VCP-associated neurodegenerative diseases.

Additionally, BRET-ID identifies G3BP1-interacting proteins in arsenite-stressed cells and tumor xenografts, uncovering novel stress granule components, including the mTORC2 subunit RICTOR. BRET-ID serves as a powerful genetically encoded tool for studying protein localization and molecular interactions in living organisms.

However, we observed that in a G3BP1/2 double knockout cell line, which strongly inhibits stress granule formation, reducing DHX36 expression rescued stress granule-like foci formation. This indicates that DHX36 can limit stress granule formation, potentially by unwinding trans-rG4s or limiting other intermolecular RNA-RNA interactions that promote stress granule formation.

Additionally, SGs can promote PCa resistance to chemotherapy, including docetaxel (DTX), through interactions with various molecules involved in apoptosis, autophagy, and metabolism. This review summarizes the roles of SGs in the development, progression, and drug resistance of PCa, building on current advances in targeting SGs, highlights their promising potential as novel therapeutic targets for inhibiting malignant cancer progression, overcoming therapeutic resistance, and advancing PCa treatment strategies.

Furthermore, we validated the overexpression of G3BP1 in cancer cells through in vitro experiments. Our study suggests that G3BP1 may serve as a diagnostic, prognostic, and immune-related biomarker in various cancers and could represent a potential target for tumour immunotherapy.

Cancerous tissues exhibited high levels of AEP and G3BP1 truncations, which were strongly associated with poor prognosis. Accordingly, this study proposed a new paradigm and potential therapeutic targets to address chemotherapy sensitivity conferred by AEP-cleaved G3BP1-mediated SGs/nucleoli/mitochondria coordination.

USP10's therapeutic significance drives inhibitor development (Spautin-1, D1, Wu-5, P22077, Parthenolide), though cross-reactivity within the USP family due to conserved catalytic domains remains a challenge. Novel strategies like PROTACs and engineered ubiquitin variants (UbVs) offer promise for future selective targeting of USP10 dysregulation in diverse diseases. A comprehensive understanding of its structure and context-specific functions is essential for exploiting its full therapeutic potential.