Fig. 2
From: Targeting PDZ domains as potential treatment for viral infections, neurodegeneration and cancer
General representation of the cellular localization of the PDZ domains controlling signaling pathways involved in cancer development and progression. (1) Tight junction and Scribble polarity complex. In epithelial cells this complex negatively regulates cell proliferation by inhibiting the expression of the key cell cycle regulator, Cyclin E, and it promotes apoptosis by blocking expression of the apoptosis inhibitor DIAP1. (2) In detail: the Frizzled receptor binds the PDZ domain of Dvl promoting the activation of Wnt signalling, with consequent activation of β-catenin dependent cell proliferation regulating cytoskeletal remodeling and cell migration. As detailed in the text, different inhibitors of Frz-7 and PDZ domain of Dvl interaction were identified and tested. (3) The principal event in tumorigenic activity of E6 protein from High-Risk Human Papillomaviruses derives from its ability to inactivate tumor suppressor p53 protein. The carcinogenic activity of high-risk HPVs is achieved through the interaction between E6 and PDZ domain of SAP-97 and Scribble proteins (4) Syntenin is a PDZ containing protein comprising a tandem of two PDZ domains, involved in cell migration, cytoskeletal rearrangement and metastasis formation. It activates the nuclear factor-kappa B (NF-kB) pathway regulating the expression of genes involved in cell motility and invasion. Monomeric peptide named KSL-128018 is reported as example of inhibitor of PDZ domains of syntenin (see details in the text). (Figure designed through BioRender.com online tool)