G3BP stress granule assembly factor 2 (G3BP2)

G3BP stress granule assembly factor 2 (G3BP2) is a multidomain RNA-binding protein that serves as a core nucleator of stress granules (SGs)—membraneless assemblies that transiently sequester translation machinery and mRNA in response to cellular stress. G3BP2 contains five critical structural motifs: the NTF2 domain for protein dimerization and nuclear transport, an acidic-rich region, multiple proline-rich (PxxP) motifs mediating protein interactions, an RNA recognition motif (RRM) for binding RNA, and an RGG domain important for protein and RNA interactions. G3BP2 regulates mRNA stabilization/degradation, nucleocytoplasmic trafficking, antiviral defense, and cellular responses to stress. Aberrant expression or mutation of G3BP2 is implicated in a variety of cancers, cardiovascular disorders, and viral pathogenesis. While not yet the focus of approved therapeutics, G3BP2 represents an emerging target for drug discovery in oncology and infectious disease.

Other names

Ras GTPase-activating protein-binding protein 2KIAA0660G3BP-2GAP SH3 domain-binding protein 2Ras-GTPase activating protein SH3 domain-binding protein 2GTPase activating protein (SH3 domain) binding protein 2

Inhibition of stress granule assembly by blocking key protein-protein or RNA interactions (e.g., targeting FGDF-binding pocket of the NTF2 domain) Disruption of nucleocytoplasmic shuttling or phase separation Modulation of mRNA decay and translation in stress response pathways