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TRIM28-Mediated SUMOylation of G3BP1/2 Regulates Stress Granule Dynamics

ABSTRACT: Stress granules (SGs) are stress-induced membraneless organelles whose dynamics are tightly regulated by protein interactions and modifications. However, whether SUMOylation directly targets SG core proteins G3BP1/2 and which ligase is involved remains unclear. Capturing these key events while preserving SG integrity is challenging due to their transient and membraneless nature. To address this, we introduce a low-concentration formaldehyde crosslinking (lcFAX) method that stabilizes membraneless organelles, including G3BP1 SGs and TDP-43 nuclear bodies, enabling enhanced proteome identification. Importantly, we identify TRIM28 as a previously undefined SG-associated protein and reveal that TRIM28 SUMOylates G3BP1 at K287 and G3BP2 at K281, establishing a critical mechanism regulating SG dynamics that ultimately impacts cellular ROS and apoptosis. lcFAX-Seq also provides insights into the RNA composition of SGs. Altogether, lcFAX-MS uncovers the critical role of TRIM28-mediated SUMOylation in modulating SG dynamics, establishing lcFAX as a powerful tool for analyzing membraneless organelles and the underlying regulatory mechanisms.

ORGANISM(S): Homo sapiens

PROVIDER: GSE286197 | GEO | 2025/09/24

REPOSITORIES: GEO

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