Segment polarity protein dishevelled homolog (DVL)

Segment polarity protein dishevelled homolog, commonly known as Dishevelled (DVL), is a family of cytoplasmic scaffold proteins (DVL1, DVL2, and DVL3) that act as central hubs in the Wnt signaling pathway [1, 5, 8]. These proteins transduce signals from extracellular Wnt ligands and their Frizzled receptors to various downstream intracellular pathways, including the canonical beta-catenin pathway and non-canonical pathways such as planar cell polarity (PCP) [1, 22]. DVL proteins are essential for embryonic development, cell fate determination, and tissue homeostasis [2, 6, 7]. In many human cancers, DVL is frequently overexpressed, driving oncogenic signaling that promotes tumor growth, metastasis, and chemoresistance [4, 10, 16]. Additionally, specific mutations in DVL genes are linked to developmental disorders like Robinow syndrome [7, 8]. Due to its pivotal role in Wnt signaling, DVL has emerged as a therapeutic target, with small molecules like FJ9 and NSC668036, as well as repositioned drugs like niclosamide and sulindac, being investigated for their ability to disrupt its protein-protein interactions or promote its degradation [16, 20, 21, 23]. However, therapeutic targeting of DVL is challenging because Wnt signaling is vital for the maintenance of high-turnover tissues like the intestinal epithelium and bone [1, 19, 27].

Other names

DishevelledDSH homologDVL1DVL2DVL3Dishevelled-1Dishevelled-2Dishevelled-3

Inhibition of the Wnt signaling pathway by disrupting the protein-protein interaction between the DVL PDZ domain and Frizzled receptors, or by promoting the degradation of DVL proteins [16, 20, 21, 23].