Disks large homolog 1 (DLG1)

Disks large homolog 1 (DLG1), also known as synapse-associated protein 97 (SAP97), is a multi-domain scaffolding protein belonging to the membrane-associated guanylate kinase (MAGUK) family. It plays a vital role in organizing signaling complexes at the plasma membrane, particularly at neuronal synapses and epithelial cell-cell junctions. DLG1 contains three PDZ domains that mediate specific protein-protein interactions; PDZ domains 1 and 3 are key modules for recruiting diverse partners such as ion channels, receptors, and viral oncoproteins. These domains are often targeted by viral factors, such as the HPV E6 protein and HTLV-1 Tax, which disrupt normal cellular scaffolding to promote viral replication and oncogenesis. In cancer, DLG1 can act as either a tumor suppressor or a promoter of migration and invasion, depending on the cellular context and its interaction partners. Therapeutic strategies targeting DLG1 focus on small molecules or peptidomimetics that inhibit the binding of pathogenic ligands to its PDZ domains. Specifically, targeting PDZ domains 1 and 3 may allow for the modulation of specific signaling pathways while sparing other critical functions, such as the tumor-suppressive interaction with APC which primarily involves PDZ domain 2.

Other names

SAP97hDLGDLGH1SAP-97Presynaptic protein SAP97Synapse-associated protein 97

Inhibition of protein-protein interactions (PPI)