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EMBO J
2012 Aug 15;3116:3384-97. doi: 10.1038/emboj.2012.181.
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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
.
???displayArticle.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.
Borchers,
Xenopus cadherin-11 restrains cranial neural crest migration and influences neural crest specification.
2001,
Pubmed
,
Xenbase
Brummelkamp,
A system for stable expression of short interfering RNAs in mammalian cells.
2002,
Pubmed
Choi,
Rap2 is required for Wnt/beta-catenin signaling pathway in Xenopus early development.
2005,
Pubmed
,
Xenbase
Clevers,
Wnt/beta-catenin signaling in development and disease.
2006,
Pubmed
Coulombe,
Atypical mitogen-activated protein kinases: structure, regulation and functions.
2007,
Pubmed
DasGupta,
Functional genomic analysis of the Wnt-wingless signaling pathway.
2005,
Pubmed
Davidson,
Kremen proteins interact with Dickkopf1 to regulate anteroposterior CNS patterning.
2002,
Pubmed
,
Xenbase
Fagotto,
Domains of axin involved in protein-protein interactions, Wnt pathway inhibition, and intracellular localization.
1999,
Pubmed
,
Xenbase
Fagotto,
Polyvalent DP1 keeps the Wnt pathway neat and tidy.
2012,
Pubmed
,
Xenbase
Harland,
In situ hybridization: an improved whole-mount method for Xenopus embryos.
1991,
Pubmed
,
Xenbase
Hassler,
Kremen is required for neural crest induction in Xenopus and promotes LRP6-mediated Wnt signaling.
2007,
Pubmed
,
Xenbase
Hayashi,
WNTs in the ovine uterus: potential regulation of periimplantation ovine conceptus development.
2007,
Pubmed
Heeg-Truesdell,
Neural induction in Xenopus requires inhibition of Wnt-beta-catenin signaling.
2006,
Pubmed
,
Xenbase
Hitchens,
The role of the transcription factor DP in apoptosis.
2003,
Pubmed
Hovanes,
Beta-catenin-sensitive isoforms of lymphoid enhancer factor-1 are selectively expressed in colon cancer.
2001,
Pubmed
Ishitani,
Homodimerization of Nemo-like kinase is essential for activation and nuclear localization.
2011,
Pubmed
Ishitani,
The TAK1-NLK-MAPK-related pathway antagonizes signalling between beta-catenin and transcription factor TCF.
1999,
Pubmed
,
Xenbase
Ishitani,
Nemo-like kinase suppresses Notch signalling by interfering with formation of the Notch active transcriptional complex.
2010,
Pubmed
,
Xenbase
Jho,
Wnt/beta-catenin/Tcf signaling induces the transcription of Axin2, a negative regulator of the signaling pathway.
2002,
Pubmed
Jooss,
Proto-oncogenic properties of the DP family of proteins.
1995,
Pubmed
Kanei-Ishii,
Wnt-1 signal induces phosphorylation and degradation of c-Myb protein via TAK1, HIPK2, and NLK.
2004,
Pubmed
Kiecker,
A morphogen gradient of Wnt/beta-catenin signalling regulates anteroposterior neural patterning in Xenopus.
2001,
Pubmed
,
Xenbase
Kim,
Essential role for beta-arrestin 2 in the regulation of Xenopus convergent extension movements.
2007,
Pubmed
,
Xenbase
Kim,
Regulation of FOXO1 by TAK1-Nemo-like kinase pathway.
2010,
Pubmed
Kim,
The protein stability of Axin, a negative regulator of Wnt signaling, is regulated by Smad ubiquitination regulatory factor 2 (Smurf2).
2010,
Pubmed
Kohn,
Dp1 is required for extra-embryonic development.
2003,
Pubmed
Lagutin,
Six3 repression of Wnt signaling in the anterior neuroectoderm is essential for vertebrate forebrain development.
2003,
Pubmed
Larraín,
Proteolytic cleavage of Chordin as a switch for the dual activities of Twisted gastrulation in BMP signaling.
2001,
Pubmed
,
Xenbase
Lee,
The roles of APC and Axin derived from experimental and theoretical analysis of the Wnt pathway.
2003,
Pubmed
,
Xenbase
Lee,
RORalpha attenuates Wnt/beta-catenin signaling by PKCalpha-dependent phosphorylation in colon cancer.
2010,
Pubmed
MacDonald,
Wnt/beta-catenin signaling: components, mechanisms, and diseases.
2009,
Pubmed
,
Xenbase
Magae,
Association with E2F-1 governs intracellular trafficking and polyubiquitination of DP-1.
1999,
Pubmed
Malbon,
Dishevelled: a mobile scaffold catalyzing development.
2006,
Pubmed
Mason,
Dorsal midline fate in Drosophila embryos requires twisted gastrulation, a gene encoding a secreted protein related to human connective tissue growth factor.
1994,
Pubmed
Masuhiro,
SOCS-3 inhibits E2F/DP-1 transcriptional activity and cell cycle progression via interaction with DP-1.
2008,
Pubmed
Morris,
E2F1 represses beta-catenin transcription and is antagonized by both pRB and CDK8.
2008,
Pubmed
Nakata,
Xenopus Zic3, a primary regulator both in neural and neural crest development.
1997,
Pubmed
,
Xenbase
Oelgeschläger,
The evolutionarily conserved BMP-binding protein Twisted gastrulation promotes BMP signalling.
2000,
Pubmed
,
Xenbase
Ohkawara,
Role of the TAK1-NLK-STAT3 pathway in TGF-beta-mediated mesoderm induction.
2004,
Pubmed
,
Xenbase
Onai,
Xenopus XsalF: anterior neuroectodermal specification by attenuating cellular responsiveness to Wnt signaling.
2004,
Pubmed
,
Xenbase
Qiao,
Human TFDP3, a novel DP protein, inhibits DNA binding and transactivation by E2F.
2007,
Pubmed
Rowland,
Re-evaluating cell-cycle regulation by E2Fs.
2006,
Pubmed
Satoh,
Nemo-like kinase-myocyte enhancer factor 2A signaling regulates anterior formation in Xenopus development.
2007,
Pubmed
,
Xenbase
Schwarz-Romond,
Dynamic recruitment of axin by Dishevelled protein assemblies.
2007,
Pubmed
Seo,
Multiple isoforms of beta-TrCP display differential activities in the regulation of Wnt signaling.
2009,
Pubmed
,
Xenbase
Suzuki,
Xenopus embryonic E2F is required for the formation of ventral and posterior cell fates during early embryogenesis.
2000,
Pubmed
,
Xenbase
Taelman,
Wnt signaling requires sequestration of glycogen synthase kinase 3 inside multivesicular endosomes.
2010,
Pubmed
,
Xenbase
Tago,
Inhibition of Wnt signaling by ICAT, a novel beta-catenin-interacting protein.
2000,
Pubmed
,
Xenbase
Tiscornia,
A general method for gene knockdown in mice by using lentiviral vectors expressing small interfering RNA.
2003,
Pubmed
Wodarz,
Mechanisms of Wnt signaling in development.
1998,
Pubmed
,
Xenbase
Yan,
Elevated expression of axin2 and hnkd mRNA provides evidence that Wnt/beta -catenin signaling is activated in human colon tumors.
2001,
Pubmed
Zeng,
Initiation of Wnt signaling: control of Wnt coreceptor Lrp6 phosphorylation/activation via frizzled, dishevelled and axin functions.
2008,
Pubmed
,
Xenbase
van den Heuvel,
Conserved functions of the pRB and E2F families.
2008,
Pubmed