Role(s) of G3BPs in Human Pathogenesis

Abstract

Ras-GTPase-activating protein (SH3 domain)-binding proteins (G3BP) are RNA binding proteins that play a critical role in stress granule (SG) formation. SGs protect critical mRNAs from various environmental stress conditions by regulating mRNA stability and translation to maintain regulated gene expression. Recent evidence suggests that G3BPs can also regulate mRNA expression through interactions with RNA outside of SGs. G3BPs have been associated with a number of disease states, including cancer progression, invasion, metastasis, and viral infections, and may be useful as a cancer therapeutic target. This review summarizes the biology of G3BP including their structure, function, localization, role in cancer progression, virus replication, mRNA stability, and SG formation. We will also discuss the potential of G3BPs as a therapeutic target. SIGNIFICANCE STATEMENT: This review will discuss the molecular mechanism(s) and functional role(s) of Ras-GTPase-activating protein (SH3 domain)-binding proteins in the context of stress granule formation, interaction with viruses, stability of RNA, and tumorigenesis.

Fig. 1.

Schematic representation of different domain structure of G3BP1 and G3BP2. Both G3BP1 and G3BP2 have an NTF2 domain at the N-terminus and an RRM/RGG domain at the C-terminus. However, G3BP1 has only one PxxP domain, whereas G3BP2a and G3BP2b contain four and five PxxP domains, respectively.

Fig. 2.

Summary of well-characterized and emerging roles of (A) G3BP1 and (B) G3BP2. (A) Different functions of G3BP1 in cancer, stress granule formation, RNA stabilization, and viral infections. (B) Different functions of G3BP2 in cancer, stress granule formation, and RNA stabilization.