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EMBO J August 15, 2012; 31 (16): 3384-97.

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

Kim WT , Kim H , Katanaev VL , Joon Lee S , Ishitani T , Cha B , Han JK , Jho EH .

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.

PubMed ID: 22773187
PMC ID: PMC3419924
Article link: EMBO J

Genes referenced: ctnnb1 dvl2 nlk tfdp1

References [+] :
Borchers, Xenopus cadherin-11 restrains cranial neural crest migration and influences neural crest specification. 2001, Pubmed, Xenbase

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