Argonaute-2 – Musashi-1 C-terminal binding interface (AGO2-MSI1 interface)

The Argonaute-2 (AGO2) – Musashi-1 (MSI1) C-terminal binding interface is a critical protein-protein interaction site involved in the post-transcriptional regulation of gene expression, particularly under cellular stress conditions such as hypoxia (Chen et al., 2020). Musashi-1 is an RNA-binding protein that, upon translocation from the nucleus to the cytosol, recruits Argonaute-2 to specific target mRNAs via its C-terminal domain (Chen et al., 2020; Lin et al., 2022). This interaction forms a complex that modulates the stability and translation of these mRNAs, often promoting oncogenic pathways by stabilizing cell-cycle promoting genes and facilitating the degradation of tumor suppressors like p53 and p21 (Chen et al., 2020). In aggressive cancers such as glioblastoma and pancreatic ductal adenocarcinoma, this interface is a key driver of tumor progression, chemoresistance, and recurrence (Chen et al., 2020). Therapeutic strategies targeting this interface, such as the development of decoy peptides like Pep#11 and Pep#26, aim to disrupt the MSI1-AGO2 complex to restore normal mRNA regulation and inhibit tumor growth (Lin et al., 2022). These peptides have demonstrated the ability to reduce tumor growth and prolong survival in animal models of glioblastoma by specifically interfering with the recruitment of the RNA-induced silencing complex (RISC) to target transcripts (Lin et al., 2022). Overall, the MSI1-AGO2 interface represents a novel and promising therapeutic target for treating refractory and stress-induced malignancies.

Other names

MSI1-AGO2 interactionMusashi-1/Argonaute-2 complexMSI1 C-terminal/AGO2 binding siteMSI1-AGO2 interface

Competitive inhibition of the protein-protein interaction between the C-terminal domain of Musashi-1 and Argonaute-2, preventing the recruitment of the RISC complex to target mRNAs (Chen et al., 2020; Lin et al., 2022).