CXXC-type zinc finger protein 5 – Dishevelled protein-protein interface (CXXC5-Dvl PPI)

CXXC-type zinc finger protein 5 (CXXC5) is a negative regulator of the Wnt/beta-catenin signaling pathway that functions by binding to the Dishevelled (Dvl) protein (UniProt Q86V15). Specifically, the C-terminal region of CXXC5 interacts with the PDZ domain of Dvl, preventing the downstream activation of the Wnt pathway (Kim et al., 2015, Nature Communications). This interaction plays a critical role in suppressing physiological processes such as hair follicle regeneration, wound healing, and osteoblast differentiation (Lee et al., 2017, J Invest Dermatol). In conditions like androgenetic alopecia or osteoporosis, CXXC5 is often overexpressed, leading to suppressed Wnt signaling. Therapeutic strategies focus on developing small molecules or peptides, such as PTD-DBM, that disrupt the CXXC5-Dvl protein-protein interface (PubMed 29104150). By inhibiting this interaction, these agents restore Wnt/beta-catenin signaling, thereby promoting hair growth and bone formation. While localized application is generally considered safe, systemic activation of the Wnt pathway carries a theoretical risk of promoting tumorigenesis, necessitating careful clinical evaluation.

Other names

CXXC5-Dvl interactionWID-Dvl interactionCXXC5-PDZ interactionZinc finger CXXC domain-containing protein 5 – Dishevelled interface

Inhibition of the protein-protein interaction between CXXC-type zinc finger protein 5 and the Dishevelled PDZ domain to activate the Wnt/beta-catenin signaling pathway.