Ras-GTPase-activating protein SH3-domain-binding protein 2 (G3BP2) (G3BP2)

Ras-GTPase-activating protein SH3-domain-binding protein 2 (G3BP2) is an RNA-binding protein that serves as a core scaffold for the assembly of stress granules, which are cytoplasmic aggregates formed during cellular stress (UniProt Q9UN86) [1]. G3BP2 plays a pivotal role in regulating mRNA stability and translation, as well as modulating various signaling pathways such as Ras and NF-κB (PubMed: 28241021) [2]. Its interaction with the SH3 domain of RasGAP is a defining feature that links it to growth factor signaling and cellular homeostasis (UniProt Q9UN86) [1]. In the context of oncology, G3BP2 is frequently overexpressed in various malignancies, including breast and prostate cancers, where it promotes tumor cell proliferation, invasion, and metastasis (PubMed: 25103441) [3]. Beyond cancer, G3BP2 is a critical host factor hijacked by numerous viruses, including SARS-CoV-2 and Chikungunya virus, to facilitate viral replication and evade host immune responses (PubMed: 32733170) [4]. Therapeutic strategies targeting G3BP2 focus on small molecules or peptides, such as C108, that disrupt its NTF2-like domain interactions, thereby inhibiting stress granule formation and associated pathological signaling (PubMed: 33854234) [5]. While no drugs are currently FDA-approved, G3BP2 remains a high-interest target for developing broad-spectrum antivirals and precision oncology treatments [5].

Other names

G3BP-2GAP SH3 domain-binding protein 2RasGAP-associated-endonuclease-like 2G3BP stress granule assembly factor 2

Inhibition of stress granule assembly and disruption of protein-protein interactions involving the NTF2-like domain to suppress oncogenic signaling or viral replication.