Anti-Dapper homolog 1

Dapper homolog 1 (DACT1) is a cytoplasmic protein and a member of DACT family. It is an important regulator in the planar cell polarity (PCP) pathway. DACT1 interacts and posttranslationally regulates central PCP components Dvl2 and Vangl2 and modulates PCP downstream of the Rac1/JNK cascade. The gene for DACT1 is located at chromosome 14q22.3, which encodes a 836 amino acid protein with a putative leucine zipper (LZ) domain in the amino-terminal end and a consensus PDZ binding (PDZ-B) motif in the carboxy-terminal end that allows the DACT1 protein to interact with the Dishevelled (Dvl) PDZ domain. DACT1 is an important positive regulator in colon cancer through regulating the stability and sublocation of Beta-catenin. The overexpression of DACT1 leads to the increased accumulation of nonphosphorylated Beta-catenin in the cytoplasm and particularly in the nuclei.It interacts with GSK-3beta and beta-catenin and stabilizes it via DACT1-induced effects on GSK-3beta which directly interacts with beta-catenin proteins. This interaction identifies DACT1 as an important positive regulator in colon cancer and suggests a potential strategy for the therapeutic control of the beta-catenin-dependent pathway. Protein function: Involved in regulation of intracellular signaling pathways during development. Specifically thought to play a role in canonical and/or non-canonical Wnt signaling pathways through interaction with DSH (Dishevelled) family proteins. The activation/inhibition of Wnt signaling may depend on the phosphorylation status. Proposed to regulate the degradation of CTNNB1/beta-catenin, thereby modulating the transcriptional activation of target genes of the Wnt signaling pathway. Its function in stabilizing CTNNB1 may involve inhibition of GSK3B activity. Promotes the membrane localization of CTNNB1. The cytoplasmic form can induce DVL2 degradation via a lysosome- dependent mechanism, the function is inhibited by PKA-induced binding to 14-3-3 proteins, such as YWHAB. Seems to be involved in morphogenesis at the primitive streak by regulating VANGL2 and DVL2, the function seems to be independent of canonical Wnt signaling and rather involves the non-canonical Wnt/planar cell polarity (PCP) pathway. The nuclear form may prevent the formation of LEF1:CTNNB1 complex and recruit HDAC1 to LEF1 at target gene promoters to repress transcription thus antagonizing Wnt signaling. May be involved in positive regulation of fat cell differentiation. During neuronal differentiation may be involved in excitatory synapse organization, and dendrite formation and establishment of spines. [The UniProt Consortium]