Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Both the RGS domain and the six C-terminal amino acids of mouse Axin are required for normal embryogenesis.
Chia IV
,
Kim MJ
,
Itoh K
,
Sokol SY
,
Costantini F
.
???displayArticle.abstract???
Axin is a negative regulator of canonical Wnt signaling, which promotes the degradation of beta-catenin, the major effector in this signaling cascade. While many protein-binding domains of Axin have been identified, their significance has not been evaluated in vivo. Here, we report the generation and analysis of mice carrying modified Axin alleles in which either the RGS domain or the six C-terminal amino acids (C6 motif) were deleted. The RGS domain is required for APC-binding, while the C6 motif has been implicated in the activation of c-Jun N-terminal kinase, but is not required for the effects of Axin on the Wnt/beta-catenin pathway, in vitro. Both mutant Axin alleles caused recessive embryonic lethality at E9.5-E10.5, with defects indistinguishable from those caused by a null allele. As Axin-DeltaRGS protein was produced at normal levels, its inability to support embryogenesis confirms the importance of interactions between Axin and APC. In contrast, Axin-DeltaC6 protein was expressed at only 25-30% of the normal level, which may account for the recessive lethality of this allele. Furthermore, many Axin(DeltaC6/DeltaC6) embryos that were heterozygous for a beta-catenin null mutation survived to term, demonstrating that early lethality was due to failure to negatively regulate beta-catenin.
Aulehla,
Wnt3a plays a major role in the segmentation clock controlling somitogenesis.
2003, Pubmed
Aulehla,
Wnt3a plays a major role in the segmentation clock controlling somitogenesis.
2003,
Pubmed
Behrens,
Functional interaction of an axin homolog, conductin, with beta-catenin, APC, and GSK3beta.
1998,
Pubmed
,
Xenbase
Brault,
Inactivation of the beta-catenin gene by Wnt1-Cre-mediated deletion results in dramatic brain malformation and failure of craniofacial development.
2001,
Pubmed
Chia,
Mouse axin and axin2/conductin proteins are functionally equivalent in vivo.
2005,
Pubmed
Fagotto,
Domains of axin involved in protein-protein interactions, Wnt pathway inhibition, and intracellular localization.
1999,
Pubmed
,
Xenbase
Hart,
Downregulation of beta-catenin by human Axin and its association with the APC tumor suppressor, beta-catenin and GSK3 beta.
1998,
Pubmed
,
Xenbase
Hsu,
Identification of a domain of Axin that binds to the serine/threonine protein phosphatase 2A and a self-binding domain.
1999,
Pubmed
Ikeda,
Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3beta and beta-catenin and promotes GSK-3beta-dependent phosphorylation of beta-catenin.
1998,
Pubmed
Itoh,
Axis determination in Xenopus involves biochemical interactions of axin, glycogen synthase kinase 3 and beta-catenin.
1998,
Pubmed
,
Xenbase
Jho,
A GSK3beta phosphorylation site in axin modulates interaction with beta-catenin and Tcf-mediated gene expression.
1999,
Pubmed
Jho,
Wnt/beta-catenin/Tcf signaling induces the transcription of Axin2, a negative regulator of the signaling pathway.
2002,
Pubmed
Julius,
Domains of axin and disheveled required for interaction and function in wnt signaling.
2000,
Pubmed
,
Xenbase
Kao,
The entire mesodermal mantle behaves as Spemann's organizer in dorsoanterior enhanced Xenopus laevis embryos.
1988,
Pubmed
,
Xenbase
Kim,
SUMOylation target sites at the C terminus protect Axin from ubiquitination and confer protein stability.
2008,
Pubmed
Kishida,
DIX domains of Dvl and axin are necessary for protein interactions and their ability to regulate beta-catenin stability.
1999,
Pubmed
Korinek,
Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma.
1997,
Pubmed
Kuan,
The Jnk1 and Jnk2 protein kinases are required for regional specific apoptosis during early brain development.
1999,
Pubmed
Lewandoski,
Conditional control of gene expression in the mouse.
2001,
Pubmed
Lewandoski,
Cre-mediated chromosome loss in mice.
1997,
Pubmed
Li,
Axin and Frat1 interact with dvl and GSK, bridging Dvl to GSK in Wnt-mediated regulation of LEF-1.
1999,
Pubmed
,
Xenbase
Liao,
Jun NH2-terminal kinase (JNK) prevents nuclear beta-catenin accumulation and regulates axis formation in Xenopus embryos.
2006,
Pubmed
,
Xenbase
Luo,
Axin: a master scaffold for multiple signaling pathways.
2004,
Pubmed
Lustig,
Negative feedback loop of Wnt signaling through upregulation of conductin/axin2 in colorectal and liver tumors.
2002,
Pubmed
Mao,
Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathway.
2001,
Pubmed
Munemitsu,
Regulation of intracellular beta-catenin levels by the adenomatous polyposis coli (APC) tumor-suppressor protein.
1995,
Pubmed
Perry,
Phenotypic and molecular analysis of a transgenic insertional allele of the mouse Fused locus.
1995,
Pubmed
Pöpperl,
Misexpression of Cwnt8C in the mouse induces an ectopic embryonic axis and causes a truncation of the anterior neuroectoderm.
1997,
Pubmed
,
Xenbase
Rui,
SUMO-1 modification of the C-terminal KVEKVD of Axin is required for JNK activation but has no effect on Wnt signaling.
2002,
Pubmed
Sabapathy,
Defective neural tube morphogenesis and altered apoptosis in the absence of both JNK1 and JNK2.
1999,
Pubmed
Salahshor,
The links between axin and carcinogenesis.
2005,
Pubmed
Weston,
The JNK signal transduction pathway.
2002,
Pubmed
Xing,
Crystal structure of a beta-catenin/axin complex suggests a mechanism for the beta-catenin destruction complex.
2003,
Pubmed
,
Xenbase
Yamamoto,
Phosphorylation of axin, a Wnt signal negative regulator, by glycogen synthase kinase-3beta regulates its stability.
1999,
Pubmed
Yang,
Absence of excitotoxicity-induced apoptosis in the hippocampus of mice lacking the Jnk3 gene.
1997,
Pubmed
Yu,
The role of Axin2 in calvarial morphogenesis and craniosynostosis.
2005,
Pubmed
Zeng,
The mouse Fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation.
1997,
Pubmed
,
Xenbase
Zhang,
Axin forms a complex with MEKK1 and activates c-Jun NH(2)-terminal kinase/stress-activated protein kinase through domains distinct from Wnt signaling.
1999,
Pubmed
Zhang,
Dimerization choices control the ability of axin and dishevelled to activate c-Jun N-terminal kinase/stress-activated protein kinase.
2000,
Pubmed
Zhang,
Differential molecular assemblies underlie the dual function of Axin in modulating the WNT and JNK pathways.
2001,
Pubmed
