title: 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/β-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/β-catenin signalling by DP1 independent from E2F. DP1 negatively regulates Wnt/β-catenin signalling by inhibiting Dvl-Axin interaction and by enhancing poly-ubiquitination of β-catenin. In contrast, DP1 positively modulates the signalling upon Wnt stimulation, via increasing cytosolic β-catenin and antagonizing the kinase activity of NLK. In Xenopus embryos, DP1 exerts both positive and negative roles in Wnt/β-catenin signalling during anteroposterior neural patterning. From subcellular localization analyses, we suggest that the dual roles of DP1 in Wnt/β-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/β-catenin signalling to determine differential cell fates.
authors: Department of Life Science, University of Seoul, Seoul, Korea.
authors: Wan-Tae
authors: WT
authors: Kim
authors: Hyunjoon
authors: H
authors: Kim
authors: Vladimir L
authors: VL
authors: Katanaev
authors: Seung
authors: S
authors: Joon Lee
authors: Tohru
authors: T
authors: Ishitani
authors: Boksik
authors: B
authors: Cha
authors: Jin-Kwan
authors: JK
authors: Han
authors: Eek-Hoon
authors: EH
authors: Jho
mesh_terms: D000818:Animals; D019521:Body Patterning; D018507:Gene Expression Regulation, Developmental; D015398:Signal Transduction; D050680:Transcription Factor DP1 / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*; D014981:Xenopus / Q000196:embryology*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D050680:Transcription Factor DP1; D051153:Wnt Proteins; D051176:beta Catenin