Dual functions of DP1 promote biphasic Wnt-on and Wnt-off states during anteroposterior neural patterning

Abstract

DP1, a dimerization partner protein of the transcription factor E2F, is known to inhibit Wnt/beta-catenin signalling along with E2F, although the function of DP1 itself was not well characterized. Here, we present a novel dual regulatory mechanism of Wnt/beta-catenin signalling by DP1 independent from E2F. DP1 negatively regulates Wnt/beta-catenin signalling by inhibiting Dvl-Axin interaction and by enhancing poly-ubiquitination of beta-catenin. In contrast, DP1 positively modulates the signalling upon Wnt stimulation, via increasing cytosolic beta-catenin and antagonizing the kinase activity of NLK. In Xenopus embryos, DP1 exerts both positive and negative roles in Wnt/beta-catenin signalling during anteroposterior neural patterning. From subcellular localization analyses, we suggest that the dual roles of DP1 in Wnt/beta-catenin signalling are endowed by differential nucleocytoplasmic localizations. We propose that these dual functions of DP1 can promote and stabilize biphasic Wnt-on and Wnt-off states in response to a gradual gradient of Wnt/beta-catenin signalling to determine differential cell fates. The EMBO Journal (2012) 31, 3384-3397. doi: 10.1038/emboj.2012.181; Published online 6 July 2012