GTPase Activating Protein (SH3 domain) Binding Protein 1, commonly referred to as G3BP1, is a multifunctional protein that plays a crucial role in various cellular processes. It is encoded by the G3BP1 gene located on chromosome 5q33.1 in humans . G3BP1 is known for its involvement in stress granule assembly, RNA binding, and regulation of microRNA processing.
G3BP1 is a member of the heterogeneous nuclear RNA-binding proteins and is involved in the Ras signal transduction pathway . It has several key domains, including the SH3 domain, which allows it to interact with other proteins and regulate their activity. G3BP1 can bind to partially unwound DNA and RNA substrates, and it exhibits endonuclease activity .
One of the primary functions of G3BP1 is its role in stress granule formation. Stress granules are cytoplasmic aggregates of proteins and RNAs that form in response to cellular stress. G3BP1 is a key component of these granules and helps in their assembly by interacting with other proteins .
G3BP1 has been shown to regulate the processing of microRNA-1 (miR-1) during cardiac hypertrophy . During cardiac hypertrophy, G3BP1 is upregulated and binds to the consensus sequence in the pre-miR-1-2 stem-loop, restricting the processing of miR-1. This results in a decrease in mature miR-1 levels and an increase in the expression of its target genes, which are essential for transcription and translation .
G3BP1 interacts with various proteins to regulate different cellular processes. For example, it interacts with USP10, a deubiquitinating enzyme, and SND1, a component of the RNA-induced silencing complex . These interactions are crucial for the regulation of stress granule assembly and other cellular functions.
The dysregulation of G3BP1 has been implicated in several diseases, including cancer and cardiac hypertrophy. Its role in stress granule formation and microRNA processing makes it a potential target for therapeutic interventions. Understanding the function and regulation of G3BP1 can provide insights into the development of novel treatments for these conditions.