axin2

Type

Gene1

Effect

Gene2

Sentence

Perturbation methods

Time of Interaction in evidence

territories of interaction or Tissue

Evidence for Direct

Authors

Journal

PubYear

Volume

Pages

MedLine Reference

Connectivity

# of References

Found In Pathways

Journal Link

Journal Reference

Mechanism

URN

ISSN

Issue

LocatorString

MedlineTA

PubMonth

p-value [Evol. Bioinformatics 2007:3(197)]

TextPath

Title

Expression

axin2

negative

chd

Expression of din (chd) at the sphere stage was inhibited by the injection of axin RNA.

overexpression

1.5

blastoderm

Hirano, T.

Mechanisms of Development

2000

293

Binding

axin2

neutral

csnk1e

Diversin recruits CKIepsilon to the eta-catenin degradation complex. ( A ) Diversin promotes association of endogenous CKIepsilon with Conductin.

Genes & Dev

59220:18:00

Zebrafish_Axin2_20080727

http://www.genesdev.org/cgi/content/full/16/16/2073

v16 i16 p2073 (2002)

urn:agi-Binding:inout-urn:agi-llid:8313:inout-urn:agi-llid:1454:

digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3051&itool=AbstractPlus-def&uid=12183362&db=pubmed&url=http://www.genesdev.org/cgi/pmidlookup?view=long&pmid=12183362

Regulation

axin2

unknown

ctnnb1

Furthermore, Axil enhanced GSK-3beta-dependent phosphorylation of beta-catenin.

egg

Yamamoto,H.;Kishida,S.;Uochi,T.;Ikeda,S.;Koyama,S.;Asashima,M.;Kikuchi,A.

J. Biol. Chem

1998

2867-75

64185:05:00

Zebrafish_ctnnb1_20080728

http://www.jbc.org/cgi/content/full/275/47/37030

v275 i47 p37030

phosphorylation

urn:agi-Regulation:inout-urn:agi-llid:8313:out-urn:agi-llid:1499::unknown:phosphorylation

0270-7306

pmquery:(Zebrafish[all+fields]+or+"Danio+rerio"[all+fields]+or+"Zebra+fish"[all+fields])1998/01/01:1999/12/31[edat]

Mol Cell Biol

May

Axil, a member of the Axin family, interacts with both glycogen synthase kinase 3beta and beta-catenin and inhibits axis formation of Xenopus embryos.

Regulation

axin2

unknown

ctnnb1

Conductin is a Wnt signalling protein and serves as a negative regulator of beta-catenin stability.

Zebrafish_Axin2_20080727

urn:agi-Regulation:inout-urn:agi-llid:8313:out-urn:agi-llid:1499::unknown

digtext:http://www.ncbi.nlm.nih.gov/pubmed/11474173?ordinalpos=16&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Regulation

axin2

positive

ctnnb1

Furthermore, Axil enhanced GSK-3beta-dependent phosphorylation of beta-catenin.

Yamamoto,H.;Kishida,S.;Uochi,T.;Ikeda,S.;Koyama,S.;Asashima,M.;Kikuchi,A.

1998

2867-75

64185:05:00

Zebrafish_Axin1_20080727

phosphorylation

urn:agi-Regulation:inout-urn:agi-llid:8313:out-urn:agi-llid:1499::positive:phosphorylation

0270-7306

pmquery:(Zebrafish[all+fields]+or+"Danio+rerio"[all+fields]+or+"Zebra+fish"[all+fields])1998/01/01:1999/12/31[edat]

Mol Cell Biol

May

Axil, a member of the Axin family, interacts with both glycogen synthase kinase 3beta and beta-catenin and inhibits axis formation of Xenopus embryos.

Regulation

axin2

positive

ctnnb1

In several tumour types, TCF/?-catenin activation is caused by mutations in either adenomatous polyposis coli (apc), ?-catenin exon 3, AXIN1, AXIN2 or ?-transducin repeat-containing protein (?-TrCP).

Zebrafish_Axin1_20080727

urn:agi-Regulation:inout-urn:agi-llid:8313:out-urn:agi-llid:1499::positive

digtext:http://www.nature.com/bjc/journal/v90/n4/full/6601589a.html

Regulation

axin2

negative

ctnnb1

Conductin induced beta-catenin degradation, whereas mutants of conductin that were deficient in complex formation stabilized beta-catenin.

52132:02:00

Zebrafish_Axin2_20080727

urn:agi-Regulation:inout-urn:agi-llid:8313:out-urn:agi-llid:1499::negative

digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3494&itool=AbstractPlus-nondef&uid=11809809&db=pubmed&url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=11809809

Expression

axin2

positive

ctnnb1

The AXIN2 gene, a negative regulator gene of Wnt/beta-catenin signaling, is a putative tumor suppressor gene on human chromosome 17q24.

43719:00:00

AllGenes-Pathway

urn:agi-Expression:inout-urn:agi-llid:8313:out-urn:agi-llid:1499::positive

digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3051&itool=AbstractPlus-def&uid=11940574&db=pubmed&url=http://www.jbc.org/cgi/pmidlookup?view=long&pmid=11940574

Expression

axin2

negative

ctnnb1

Because Axin2 can inhibit beta-catenin abundance and function, the data implicate AXIN2 in a negative feedback pathway regulating Wnt signaling.

Leung,J.Y.;Kolligs,F.T.;Wu,R.;Zhai,Y.;Kuick,R.;Hanash,S.;Cho,K.R.;Fearon,E.R.

2002

277

21657-65

13022:07:00

AllGenes-Pathway

urn:agi-Expression:inout-urn:agi-llid:8313:out-urn:agi-llid:1499::negative

0021-9258

pmquery:(Zebrafish[all+fields]+or+"Danio+rerio"[all+fields]+or+"Zebra+fish"[all+fields])2002/01/01:2002/12/31[edat]

J Biol Chem

Jun

Activation of AXIN2 expression by beta-catenin-T cell factor. A feedback repressor pathway regulating Wnt signaling.

Binding

axin2

neutral

ctnnb1

Here, the protein conductin was found to form a complex with both beta-catenin and the tumor suppressor gene product adenomatous polyposis coli (apc).

EMBO

52132:01:00

Zebrafish_Axin2_20080727

http://www.nature.com/emboj/journal/v24/n1/full/7600460a.html

v24 i1 p7600460

urn:agi-Binding:inout-urn:agi-llid:8313:inout-urn:agi-llid:1499:

digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3494&itool=AbstractPlus-nondef&uid=12072559&db=pubmed&url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=12072559

Expression

axin2

negative

dharma

Expression of din (chd) at the sphere stage was inhibited by the injection of axin RNA.

overexpression

1.5

blastoderm

Hirano, T.

Mechanisms of Development

2000

293

Expression

axin2

negative

gsc

overexpression of Axin reduced the dorsal expression of boz/dharma at both the sphere and shield stages.

overexpression

YSL

Hirano, T.

Mechanisms of Development

2000

293

Regulation

axin2

positive

gsk3b

DISCUSSION Top Abstract Introduction Materials and Methods Results Discussion References Both Axin and its homolog Axin2/Conductin/Axil are believed to act as scaffold proteins, which bind several components of the canonical Wnt signal transduction pathwa

Mol. Cell. Biol

13498:24:00

Zebrafish_Axin2_20080727

http://mcb.asm.org/cgi/content/full/22/4/1172

v22 i4 p1172

urn:agi-Regulation:inout-urn:agi-llid:8313:out-urn:agi-llid:2932::positive

digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3494&itool=AbstractPlus-nondef&uid=11809808&db=pubmed&url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=11809808

Binding

axin2

neutral

gsk3b

Axil bound not only to GSK-3beta but also to beta-catenin, and the GSK-3beta-binding site of Axil was distinct from the beta-catenin-binding site.

egg

Mol. Cell. Biol

64185:04:00

Zebrafish GRN from literatures-7-24-2008

http://mcb.asm.org/cgi/content/full/25/11/4371

v25 i11 p4371

urn:agi-Binding:inout-urn:agi-llid:8313:inout-urn:agi-llid:2932:

digtext:C:\Documents and Settings\yuh\My Documents\MedScan Reader Projects\zebrafish development\Tzu-Min's old papers\Toshio Hirano 2000.pdf

url(C%3a%5cDocuments%20and%20Settings%5cyuh%5cMy%20Documents%5cMedScan%20Reader%20Projects%5czebrafish%20development%5cTzu-Min%27s%20old%20papers%5cToshio%20Hirano%202000.pdf):pdf

Expression

axin2

positive

lef1

The presence of core Tcf/LEF binding sites in promoter/intron 1 sequences of human and mouse Axin2, together with the induction of Axin2 mRNA by Wnts (Fig. 2), suggested that Axin2 expression is regulated via Tcf/LEF transcription factors.

Zebrafish_Axin2_20080727

urn:agi-Expression:inout-urn:agi-llid:8313:out-urn:agi-protfc:LEF::positive

Expression

axin2

negative

lef1

As shown in Fig. 9, whereas the ability of wild type ?-catenin to activate TCF transcription was strongly inhibited by Axin2, the S33Y mutant form of ?-catenin was not significantly inhibited by Axin2.

Zebrafish_Axin1_20080727

urn:agi-Expression:inout-urn:agi-llid:8313:out-urn:agi-protfc:LEF::negative

digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3051&itool=AbstractPlus-def&uid=11940574&db=pubmed&url=http://www.jbc.org/cgi/pmidlookup?view=long&pmid=11940574

Expression

axin2

negative

lfng

In accord with this hypothesis, beads coated with Wnt3a -expressing cells alter the spacing of somite boundarie s in chick embryos, and misexpression of Axin2 at a steady level in the PSM of transgenic mice severely impairs the cycling of lfng expression.

Zebrafish GRN from literatures-7-24-2008

urn:agi-Expression:inout-urn:agi-llid:8313:out-urn:agi-llid:3955::negative

digtext:C:\Documents and Settings\yuh\Desktop\zebrafish GRN Literatures\Lewis-J-2004.pdf

url(C%3a%5cDocuments%20and%20Settings%5cyuh%5cDesktop%5czebrafish%20GRN%20Literatures%5cLewis-J-2004.pdf):pdf

Binding

axin2

neutral

wnt

We investigated the response of GSK3eta in the axin-conductin complex to insulin or Wnt.

Katoh,M.;Katoh,M.

J. Biol. Chem

2005

1045-9

34347:02:00

Zebrafish_Axin1_20080727

http://www.jbc.org/cgi/content/full/275/42/32475

v275 i42 p32475

urn:agi-Binding:inout-urn:agi-llid:8313:inout-urn:agi-go:0042813:

1107-3756

pmquery:(Zebrafish[all+fields]+or+"Danio+rerio"[all+fields]+or+"Zebra+fish"[all+fields])2005/01/01:2005/06/30[edat]

Int J Mol Med

Jun

Identification and characterization of rat dact1 and Dact2 genes in silico.

Regulation

ankrd6

positive

axin2

Coimmunoprecipitation experiments showed that full-length Diversin promotes the association of CKIepsilon with Conductin in 293 cells (Fig. 3 A).

Genes & Dev

59370:07:00

Zebrafish_Axin2_20080727

http://www.genesdev.org/cgi/content/full/16/16/2073

v16 i16 p2073

urn:agi-Regulation:inout-urn:agi-llid:22881:out-urn:agi-llid:8313::positive

digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3051&itool=AbstractPlus-def&uid=12183362&db=pubmed&url=http://www.genesdev.org/cgi/pmidlookup?view=long&pmid=12183362

Binding

ankrd6

neutral

axin2

Further analyses showed that Diversin interacts directly with Conductin or Axin and with CKIepsilon.

Genes & Dev

59369:20:00

Zebrafish_Axin2_20080727

http://www.genesdev.org/cgi/content/full/16/16/2073

v16 i16 p2073

urn:agi-Binding:inout-urn:agi-llid:8313:inout-urn:agi-llid:22881:

digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3051&itool=AbstractPlus-def&uid=12183362&db=pubmed&url=http://www.genesdev.org/cgi/pmidlookup?view=long&pmid=12183362

Expression

apc

positive

axin2

To assess the effects of wild type apc gene function on AXIN1 and AXIN2 gene expression, HT29/eta-Gal and HT29/apc cells were treated with 150 µ M ZnCl 2 for induction of the control lacZ and wild type apc genes, respectively.

J. Biol. Chem

13189:58:00

Zebrafish_Axin1_20080727

http://www.jbc.org/cgi/content/full/277/24/21657

v277 i24 p21657

urn:agi-Expression:inout-urn:agi-llid:324:out-urn:agi-llid:8313::positive

digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3051&itool=AbstractPlus-def&uid=11940574&db=pubmed&url=http://www.jbc.org/cgi/pmidlookup?view=long&pmid=11940574

Binding

axin1

neutral

axin2

We show that Diversin recruits the priming kinase CKIepsilon to the Axin/Conductin-GSK3eta complex (see scheme in Fig. 6 A).

Genes & Dev

59371:46:00

Zebrafish GRN from literatures-7-24-2008

http://www.genesdev.org/cgi/content/full/16/16/2073

v16 i16 p2073

urn:agi-Binding:inout-urn:agi-llid:8313:inout-urn:agi-llid:8312:

digtext:C:\Documents and Settings\yuh\My Documents\MedScan Reader Projects\zebrafish development\Tzu-Min's old papers\Toshio Hirano 2000.pdf

url(C%3a%5cDocuments%20and%20Settings%5cyuh%5cMy%20Documents%5cMedScan%20Reader%20Projects%5czebrafish%20development%5cTzu-Min%27s%20old%20papers%5cToshio%20Hirano%202000.pdf):pdf

Expression

ctbp1

negative

axin2

CtBP1 down-regulates the expression of Axin2, a Tcf/?-catenin target in 293 cells We examined the expression levels of several human genes related to Wnt signaling in Wnt-1-stimulated 293 cells.

Zebrafish_Axin2_20080727

urn:agi-Expression:inout-urn:agi-llid:1487:out-urn:agi-llid:8313::negative

digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3494&itool=AbstractPlus-nondef&uid=12711682&db=pubmed&url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=12711682

Regulation

ctnnb1

positive

axin2

Through analysis of gene expression profiles generated from the colon cancer cell line SW620 with reduced ?-catenin protein levels resulting from antisense oligodeoxynucleotide (ODN) transfection, we found that axin2 and hnkd are ?-catenin-induced target

Zebrafish_Axin2_20080727

urn:agi-Regulation:inout-urn:agi-llid:1499:out-urn:agi-llid:8313::positive

digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3494&itool=AbstractPlus-nondef&uid=11752446&db=pubmed&url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=11752446

Expression

ctnnb1

neutral

axin2

Analysis of the beta-catenin target genes Axin2 and Tcf-4 confirmed increased beta-catenin-dependent transcription in beta-catenin stabilized mice.

46004:05:00

AllGenes-Pathway

urn:agi-Expression:inout-urn:agi-llid:1499:out-urn:agi-llid:8313::unknown

Expression

ctnnb1

positive

axin2

TCF binding sites in the AXIN2 promoter played a key role in the ability of beta-catenin to activate AXIN2 transcription.

Leung,J.Y.;Kolligs,F.T.;Wu,R.;Zhai,Y.;Kuick,R.;Hanash,S.;Cho,K.R.;Fearon,E.R.

Mol. Cell. Biol

2002

277

21657-65

13022:05:00

AllGenes-Pathway

http://mcb.asm.org/cgi/content/full/25/11/4371

v25 i11 p4371

urn:agi-Expression:inout-urn:agi-llid:1499:out-urn:agi-llid:8313::positive

0021-9258

pmquery:(Zebrafish[all+fields]+or+"Danio+rerio"[all+fields]+or+"Zebra+fish"[all+fields])2002/01/01:2002/12/31[edat]

J Biol Chem

Jun

Activation of AXIN2 expression by beta-catenin-T cell factor. A feedback repressor pathway regulating Wnt signaling.

Regulation

dvl2

positive

axin2

Transfection of the upstream activator of Wnt signaling, dishevelled-2 ( 28 ), into Neuro2A cells resulted in a significant upregulation of conductin (Fig. 5E ).

Mol. Cell. Biol

13498:45:00

Zebrafish_Axin2_20080727

http://mcb.asm.org/cgi/content/full/22/4/1184

v22 i4 p1184

urn:agi-Regulation:inout-urn:agi-llid:1856:out-urn:agi-llid:8313::positive

ProtModification

gsk3b

phosphorylation

axin2

Axil was phosphorylated by GSK-3beta.

egg

64185:03:00

Zebrafish_wnt8a_20080804

phosphorylation

urn:agi-ProtModification:inout-urn:agi-llid:2932:out-urn:agi-llid:8313::unknown:phosphorylation

ProtModification

gsk3b

phosphorylation

axin2

Axil was phosphorylated by GSK-3beta.

Yamamoto,H.;Kishida,S.;Uochi,T.;Ikeda,S.;Koyama,S.;Asashima,M.;Kikuchi,A.

1998

2867-75

64185:03:00

Zebrafish_ctnnb1_20080728

phosphorylation

urn:agi-ProtModification:inout-urn:agi-llid:2932:out-urn:agi-llid:8313::unknown

0270-7306

pmquery:(Zebrafish[all+fields]+or+"Danio+rerio"[all+fields]+or+"Zebra+fish"[all+fields])1998/01/01:1999/12/31[edat]

Mol Cell Biol

May

Axil, a member of the Axin family, interacts with both glycogen synthase kinase 3beta and beta-catenin and inhibits axis formation of Xenopus embryos.

Expression

jup

positive

axin2

We found that the rat Axil gene was strongly induced upon neoplastic transformation of RK3E cells by mutant beta-catenin or gamma-catenin or after ligand-induced activation of a beta-catenin-estrogen receptor fusion protein.

13022:02:00

Zebrafish_Axin1_20080727

urn:agi-Expression:inout-urn:agi-llid:3728:out-urn:agi-llid:8313::positive

digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3051&itool=AbstractPlus-def&uid=11940574&db=pubmed&url=http://www.jbc.org/cgi/pmidlookup?view=long&pmid=11940574

Expression

lef1

positive

axin2

TCF binding sites in the AXIN2 promoter played a key role in the ability of beta-catenin to activate AXIN2 transcription.

Mol. Cell. Biol

13022:05:00

Zebrafish_Axin1_20080727

http://mcb.asm.org/cgi/content/full/25/11/4371

v25 i11 p4371

urn:agi-Expression:inout-urn:agi-protfc:LEF:out-urn:agi-llid:8313::positive

digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3051&itool=AbstractPlus-def&uid=11940574&db=pubmed&url=http://www.jbc.org/cgi/pmidlookup?view=long&pmid=11940574

Expression

tcf7l2

negative

axin2

Human colon cancer cell lines had elevated AXIN2 expression, and restoration of apc function or expression of a dominant negative form of TCF-4 in the cells strongly inhibited AXIN2 expression.

Zebrafish_Axin1_20080727

urn:agi-Expression:inout-urn:agi-llid:6925:out-urn:agi-llid:8313::negative

digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3051&itool=AbstractPlus-def&uid=11940574&db=pubmed&url=http://www.jbc.org/cgi/pmidlookup?view=long&pmid=11940574

Expression

tcf7l2

positive

axin2

In addition, TCF4 and conductin are coexpressed in the crypt epithelium and in the polyps, which suggests that TCF4 could be an activator of conductin gene transcription.

Zebrafish_Axin2_20080727

urn:agi-Expression:inout-urn:agi-llid:6925:out-urn:agi-llid:8313::positive

Expression

wnt

positive

axin2

Additionally, although Axin1 and Axin2 have been thought to have comparable functions, the observation that Wnt pathway activation elevates AXIN2 but not AXIN1 expression suggests that there may be potentially significant functional differences between th

mesenchyma

Mol. Cell. Biol

13022:08:00

Zebrafish_Axin1_20080727

http://mcb.asm.org/cgi/content/full/22/4/1184

v22 i4 p1184

urn:agi-Expression:inout-urn:agi-go:0042813:out-urn:agi-llid:8313::positive

digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3051&itool=AbstractPlus-def&uid=11940574&db=pubmed&url=http://www.jbc.org/cgi/pmidlookup?view=long&pmid=11940574

Expression

wnt

neutral

axin2

While expression of conductin is clearly regulated by Wnt signaling, expression of the related protein axin appaears to be constitutive.

Zebrafish_Axin2_20080727

urn:agi-Expression:inout-urn:agi-go:0042813:out-urn:agi-llid:8313::unknown

Expression

wnt1

positive

axin2

Expression of Wnt1 in murine breast epithelial cells activated the conductin gene, and human cancers with defective beta-catenin regulation had elevated AXIN2 gene and protein expression.

epithelia

Mol. Cell. Biol

13022:03:00

AllGenes-Pathway

http://mcb.asm.org/cgi/content/full/22/4/1172

v22 i4 p1172

urn:agi-Expression:inout-urn:agi-llid:7471:out-urn:agi-llid:8313::positive

digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3051&itool=AbstractPlus-def&uid=11940574&db=pubmed&url=http://www.jbc.org/cgi/pmidlookup?view=long&pmid=11940574

Expression

wnt5b

negative

axin2

Fig. 4. b-catenin-dependent and b-catenin-independent Wnt signaling pathways have opposing roles in zebrafish fin regeneration. (A,D) Overexpression of Wnt8 in hsWnt8GFP transgenic fish induces the Wnt/?-catenin target gene axin2 in regenerating fins 6 ho

Zebrafish_Axin1_20080727

urn:agi-Expression:inout-urn:agi-llid:81029:out-urn:agi-llid:8313::negative

digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3051&itool=AbstractPlus-def&uid=17185322&db=pubmed&url=http://dev.biologists.org/cgi/pmidlookup?view=long&pmid=17185322