Dishevelled-binding antagonist of beta-catenin 3 (DACT3)

Dishevelled-binding antagonist of beta-catenin 3 (DACT3) is a cytoplasmic protein that functions as a negative regulator of the canonical and non-canonical Wnt/β-catenin signaling pathways by interacting with Dishevelled (DSH/DVL) family proteins[1][3][7]. DACT3 downregulates Wnt pathway activity, leading to decreased cell proliferation and induction of apoptosis, and has been identified as a tumor suppressor in contexts such as colorectal cancer and acute myeloid leukemia[1][2]. Its repression in cancer is associated with bivalent histone modifications rather than DNA methylation, and pharmacological de-repression (e.g., with DZNep and TSA) restores DACT3 expression, negatively regulating Wnt signaling and promoting cancer cell death[1]. DACT3 is part of the DACT protein family and plays important roles in intracellular developmental signaling cascades, cell adhesion, and migration[3][4][7].

Other names

Dapper homolog 3DACT3RRR1MGC15476DAPPER3Antagonist of beta-catenin Dapper homolog 3Arginine-rich region 1 proteinDapper antagonist of catenin 3dapper homolog 3antagonist of beta-catenin Dapper homolog 3arginine-rich region 1 proteindapper, antagonist of beta-catenin, homolog 3DACT3[3][7]

For drugs like DZNep and TSA: Epigenetic de-repression of DACT3 by inhibiting repressive histone methylation and deacetylation, restoring its ability to antagonize Wnt/β-catenin signaling, leading to decreased cell growth and increased apoptosis[1].