The Wnt genes are a group of well conserved, cysteine-rich secreted glycoproteins that are required for numerous developmental processes including embryogenesis, asymmetric cell division and central nervous system (CNS) patterning. Wnt association with the seven membrane spanning receptor frizzled activates dishevelled, which downregulates glycogen synthase kinase (GSK) through serine phosphorylation, causing the accumulation of b-catenin and subsequent regulation of developmentally significant Wnt |target genes. The Dickkopf family of secreted inhibitors of Wnt signaling ensures proper morphological development by antagonizing different stages of the Wnt cascade. Dkk-1 (Dickkopf-1) acts upstream of b-catenin and dishevelled to inhibit Wnt signaling. Dkk-1 is a 266-amino acid (human), secreted protein that contains a 31-residue N-terminal signal peptide, 2 cysteine rich domains, and a putative carboxy terminal N-glycosylation site. Human Dkk-1 transcripts are abundantly present in fetal kidney, adult placenta and adult prostate. Putative cis regulatory elements upstream of the Dkk-1 start site include p53, Sp1, MyoD, STAT, Oct-1/2, C/EBP-a, C/EBP-b, GATA-1, GATA-2 and GATA-3.
