Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 1 (MAGI-1) (MAGI-1)

Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 1 (MAGI-1) is a multi-domain scaffolding protein that plays a pivotal role in the organization of protein complexes at cell-cell junctions (UniProt Q96QZ7). It is characterized by the presence of six PDZ domains, which serve as versatile modules for protein-protein interactions, particularly with the C-terminal motifs of various signaling and structural proteins (PubMed: 11836245). MAGI-1 is essential for the maintenance of tight junctions and the regulation of cell polarity, making it a key player in epithelial and endothelial integrity. In clinical contexts, MAGI-1 is a well-known target of high-risk human papillomavirus (HPV) E6 oncoproteins, which bind to its PDZ domains and trigger its proteasomal degradation, a process that contributes to viral-induced oncogenesis (PubMed: 10906120). Beyond viral infections, MAGI-1 acts as a tumor suppressor in several cancers, and its dysregulation is associated with inflammatory conditions and neurological disorders (PubMed: 25863144). Current therapeutic research explores the use of peptidomimetics and small molecules designed to competitively inhibit the binding of pathogenic ligands to MAGI-1 PDZ domains, thereby preserving its structural and signaling functions.

Other names

MAGI1BAI1-associated protein 1BAIAP1Atrophin-1-interacting protein 3AIP3Trinucleotide repeat-containing gene 19 proteinBAP-1

Inhibition of protein-protein interactions (PPI) by blocking the PDZ domain binding pockets to prevent pathogenic degradation or to stabilize signaling complexes.