Axin-1 (axis inhibition protein 1) is a scaffold protein that is involved in many signalling pathways, including the Wnt, transforming growth factor-beta, MAP kinase pathways, as well as p53 activation cascades [, ]. It controls many biological processes ranging from sugar intake, cell proliferation, and organ development to cell death [].Mutations in Axin-1 gene cause hepatocellular carcinoma (HCC), a primary malignant neoplasm of epithelial liver cells [], and caudal duplication anomaly (CADUA), a condition characterised by the occurrence of duplications of different organs in the caudal region [].
This entry includes the dishevelled (Dsh) proteins and dixin (also known as coiled-coil-DIX1, Ccd1).The transduction mechanism requires dishevelled protein (Dsh), a cytoplasmic phosphoprotein that acts directly downstream of frizzled []. In addition to its role in Wnt signalling, Dsh is also involved in generating planar polarity in Drosophila and has been implicated in the Notch signal transduction cascade. Furthermore, Dsh plays a vital molecular role in neural tube closure. Disruption of dishevelled signalling in Xenopus and inactivation of the genes encoding dishevelled 1 and dishevelled 2 (Dvl1 and Dvl2) in the mouse yield similar phenotypes, in which the neural tube fails to close []. Three human and mouse homologues of Dsh have been cloned (DVL-1 to 3); it is believed that these proteins, like their Drosophila counterpart, are involved in signal transduction. Human and murine orthologues share more than 95% sequence identity and are each 40-50% identical to Drosophila Dsh.Sequence similarity amongst Dsh proteins is concentrated around three conserved domains: at the N terminus lies a DIX domain (mutations mapping to this region reduce or completely disrupt Wg signalling); a PDZ (or DHR) domain, often found in proteins involved in protein-protein interactions, lies within the central portion of the protein (point mutations within this module have been shown to have little effect on Wg-mediated signal transduction); and a DEP domain is located towards the C terminus and is conserved among a set of proteins that regulate various GTPases. Whilst genetic and molecular assays have shown this module to be dispensable for Wg signalling, it is thought to be important in planar polarity signalling in flies [].Ccd1 is another DIX domain-possessing protein that forms complexes with the Dishevelled homologue Dvl and Axin. Ccd1 is a positive regulator of Wnt signalling []. It regulates JNK activation by AXIN1 and DVL2 [].
