Dual functions of DP1 promote biphasic Wnt-on and Wnt-off states during anteroposterior neural patterning.
EMBO J
; 31(16): 3384-97, 2012 Aug 15.
Article
em En
| MEDLINE
| ID: mdl-22773187
ABSTRACT
DP1, a dimerization partner protein of the transcription factor E2F, is known to inhibit Wnt/ß-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/ß-catenin signalling by DP1 independent from E2F. DP1 negatively regulates Wnt/ß-catenin signalling by inhibiting Dvl-Axin interaction and by enhancing poly-ubiquitination of ß-catenin. In contrast, DP1 positively modulates the signalling upon Wnt stimulation, via increasing cytosolic ß-catenin and antagonizing the kinase activity of NLK. In Xenopus embryos, DP1 exerts both positive and negative roles in Wnt/ß-catenin signalling during anteroposterior neural patterning. From subcellular localization analyses, we suggest that the dual roles of DP1 in Wnt/ß-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/ß-catenin signalling to determine differential cell fates.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Xenopus
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Regulação da Expressão Gênica no Desenvolvimento
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Padronização Corporal
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Proteínas Wnt
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Fator de Transcrição DP1
Limite:
Animals
Idioma:
En
Revista:
EMBO J
Ano de publicação:
2012
Tipo de documento:
Article