GTPase Activating Protein (SH3 domain) Binding Protein 2 (G3BP2) is a member of the G3BP family, which also includes G3BP1. These proteins are known for their role in various cellular processes, including stress granule formation, RNA metabolism, and signal transduction. G3BP2 is encoded by the G3BP2 gene located on human chromosome 4. The protein is highly expressed in the small intestine and brain .
G3BP2 is an RNA-binding protein that interacts with the SH3 domain of Ras-GTPase activating protein (Ras-GAP) in serum-stimulated cells . The protein consists of several domains, including an NTF2-like domain, an RNA recognition motif (RRM), and an acidic C-terminal region. These domains facilitate its interactions with various cellular components and its involvement in multiple cellular pathways.
One of the key functions of G3BP2 is its role in the formation of stress granules (SGs). Stress granules are membraneless organelles that form in response to cellular stress and serve as storage sites for mRNAs and proteins . G3BP2 promotes the assembly of these granules through liquid-liquid phase separation (LLPS), a process driven by the interaction of its RNA-binding domains with unfolded RNA .
G3BP2 plays a crucial role in the regulation of mRNA stability and translation. It acts as a molecular switch that triggers RNA-dependent LLPS in response to increased intracellular RNA concentrations . This function is essential for the formation of stress granules, which help cells survive under stress conditions by sequestering and protecting mRNAs.
In addition to its role in stress granule formation, G3BP2 is involved in various signaling pathways. It interacts with the Ras signaling pathway, although the exact nature of this interaction is still under investigation . G3BP2 also participates in the innate immune response by promoting the activity of cGAS and RIG-I, two key components of the antiviral defense mechanism .
G3BP2 has been implicated in several diseases, including cancer, neurodevelopmental disorders, and viral infections. Its role in stress granule formation and RNA metabolism makes it a potential target for therapeutic interventions. For example, modulating G3BP2 activity could help enhance the antiviral response or mitigate the effects of cellular stress in diseases such as cancer .