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AXIN1 (axin 1)

Identity

Other namesAXIN
MGC52315
HGNC (Hugo) AXIN1
LocusID (NCBI) 8312
Location 16p13.3
Location_base_pair Starts at 337440 and ends at 402676 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Note According to Entrez gene and Ensembl the isoform a starts at 337440 and ends at 402464 bp with the total lenght of 65025 bp. The isoform b starts at 338122 and ends at 397025 with the total lenght of 58904 bp. Zeng et al. (1997) renamed the gene that was originally termed Fu to Axin in order to avoid confusion with the unrelated Drosophila gene fused.

DNA/RNA

 
  Figure 1. Genomic structure of Axin 1. Axin 1 is composed of 10 exons and they encode isoform a, while in isoform b exon 8 is spliced out.
Description Axin 1 consists of 11 exons (isoform a). Full gene transcript product length is 3675 bp. Isoform b lacks an in-frame exon in the 3' coding region and is shorter with sequence length of 3567 bp (Salahshor and Woodgett, 2005) (Figure 1).
Transcription There are two transcript variants. Variant 1 (encoding for isoform a) represents the longer transcript (NM 003502.3). Variant 2 (encoding for isoform b) is shorter compared to variant 1 (NM 181050.2). According to Ensembl there are six transcripts of AXIN1 of which first two are well known isoforms a and b and the remaining 4 are still in research.

Protein

Note Protein name: Axin 1, Axin, Axis inhibitor, Axis inhibitor protein 1.
Description At least two isoforms of protein axin are expressed. Longer isoform has all eleven exons translated and consists of 862 aminoacids while shorter has 826 aminoacids translated from ten exons. Axin 1 protein can be recognized primarily by two domains, the N-terminal RGS domain (regulators of G-protein signaling) and the C-terminal DIX domain (dishevelled and axin) (Luo et al., 2005; Shibata et al., 2007). RGS domain is needed for APC binding while DIX domain for homodimerization and heterodimerization (Ehebauer and Arias, 2009; Noutsou et al., 2011). There is also a central region of the protein that binds GSK3beta and beta-catenin. Axin protein has nuclear localization (NLS) and nuclear export (NES) sequences as well. It is well known that axin is a scaffold protein that can shuttle between the cytoplasm and the nucleus. Nucleo-cytoplasmatic shuttling under normal circumstances suggests existence of possible "salvage pathway" that would be activated by axin translocation to the nucleus in order to reduce beta-catenin oncogenic activity by exporting nuclear beta-catenin and degrading it in the cytoplasm (Wiechens et al., 2004). Axin can also undergo posttranslational modifications. Phosphorilation by casein kinase 1 (CK1) enhances binding of GSK3beta and AXIN1. For activation of JNK pathway axin needs to be SUMOylated (Kim et al., 2008) (Figure 2).
 
  Figure 2. Two crystallized domains of the Axin 1 protein are shown: (A) RGS and (B) DIX.
Expression Axin is expressed ubiquitously.
Localisation Axin is predominantlly expressed in the cytoplasm, but periplasmic and nuclear localization are also observed depending on the stimulation of the cells (Cong and Varmus, 2004; Luo and Lin, 2004). In nonstimulated cells, axin colocalizes with Smad3. The subcellular location of axin is not well defined in the literature. It has been reported that physiological concentrations of axin is low in Xenopus egg cells. It has also been shown that it is located in cytoplasmic puncta in living mammalian cells. Wang et al. (2009) report that axin 1 is highly co-localized with beta-catenin in the cytoplasm of human cumulus cells and that this localization denotes intact wnt signaling. Pecina-Slaus et al. (2011) showed the subcellular location of axin in normal brain white matter and glioblastoma tissue. The majority of glioblastomas (69.04%) had axin localized in the cytoplasm. Nevertheless, 9.5% of glioblastomas samples had axin localized in the nucleus (Figure 3). Distribution of axin was reported previously by Anderson et al. (2002) in neoplastic colon. Altered nuclear expression of axin seen in colon polyps and carcinomas may be a consequence of the loss of full-length APC and the advent of nuclear beta-catenin.
 
  Figure 3. Glioblastoma samples immunohistochemically stained for protein expression of axin. (A) Cytoplasmic localization of axin and (B) nuclear localization of axin.
Function Tumor suppressor protein Axin 1 is an inhibitor of the Wnt signaling pathway (Polakis, 2000; Salahshor and Woodgett, 2005). As a scaffold protein, its main role is binding multiple members of Wnt signaling and formation of the beta-catenin destruction complex. It down-regulates beta-catenin, wnt pathway's main effector signaling molecule, by facilitating its phosphorylation by GSK3-beta (Hart et al., 1998). It binds directly to APC (adenomatous polyposis coli), beta-catenin, GSK3-beta and dishevelled forming a so called "beta-catenin destruction complex" in which phosphorylated beta-catenin is targeted for quick ubiquitinilation and degradation in the 26S proteosome (Yamamoto et al., 1999; Logan and Nusse, 2004). In response to wnt signaling, or under the circumstances of mutated axin or APC, beta-catenin is stabilized, accumulates in the cytoplasm and enters the nucleus, where it finds a partner, a member of the DNA binding protein family LEF/TCF. Together they stimulate the expression of target genes including c-myc, c-jun, fra-1 and cyclin D1. In developement Axin controls dorsoventral polarity axis formation (Zeng et al., 1997; Wodarz and Nusse, 1998) by two independent mechanisms: downregulation of beta-catenin, but also by activation of Wnt-independent JNK signaling activation. Axin has a role in determining cell's fate upon damage, haematopoetic stem cells differentiation (Reya et al., 2003) and transforming growth factor beta signaling (Furuhashi et al., 2001). Reports indicate that beta-catenin and axin regulate critical developmental processes of normal CNS development (Pecina-Slaus, 2010).
Axin interacts with a number of proteins including: APC, Axam, Axin, beta-catenin, Ccd1, CKI, DAXX, DCAP, Diversin, Dvl, gamma-tubulin, GSK3beta, HIPK2, I-mfa, LRP5/LRP6, MDFIC, MEKK1, MEKK4, P53, PIAS, Pirh2, PP2A, Rnf11, Zbed3, Tip60, Smad3, Smad6, and Smad7 (Cliffe et al., 2003; Chen et al., 2009; Fumoto et al., 2009; Li et al., 2009; Choi et al., 2010; Kim and Jho, 2010).
Homology Homologs are found in: Pan troglodytes, Canis lupus familiaris, Bos taurus, Mus musculus, Rattus norvegicus, Gallus gallus, Danio rerio.

Mutations

Note According to HGMD there are 3 missense mutations reported for AXIN 1 in colorectal carcinoma. Nikuseva Martic et al. (2010) identified gross deletions (Loss of Heterozygosity) of AXIN 1 in 6.3% of glioblastomas, in one neuroepithelial dysembrioplastic tumor and in one medulloblastoma. In a primary hepatocellular carcinoma 13 somatic events were reported by OMIM, a 33-bp deletion in exon 3 of the AXIN1 gene, and 12 missense mutations. OMIM also reports on hypermethylation of AXIN 1 promotor region in caudal duplication anomaly.

Implicated in

Entity Hepatocellular carcinoma
Note In a primary hepatocellular carcinoma (HCC), Satoh et al. (2000) found a 33-bp deletion in exon 3 of the AXIN1 gene, involving 2 glycogen synthase kinase-3-beta phosphorylation sites. In addition to this deletion they found 12 missense mutations, of which 9 occurred in codons encoding serine or threonine residues. They confirmed that all 13 mutations found in primary HCCs occurred as somatic events. Taniguchi et al. (2002) found AXIN1 mutations in seven (9.6%) HCCs. The AXIN1 mutations included seven missense mutations, a 1 bp deletion, and a 12 bp insertion. Loss of heterozygosity at the AXIN1 locus was present in four of five informative HCCs with AXIN1 mutations, suggesting a tumor suppressor function of this gene. Park et al. (2005) showed that mutations of AXIN 1 are late events in hepatocellular carcinogenesis.
  
Entity Medulloblastoma
Note To find out if Axin is also involved in the pathogenesis of sporadic medulloblastomas, Dahmen et al. (2001) analyzed 86 cases and 11 medulloblastoma cell lines for mutations in the AXIN1 gene. Using single-strand conformation polymorphism analysis, screening for large deletions by reverse transcription-PCR, and sequencing analysis, a single somatic point mutation in exon 1 (Pro255Ser) and seven large deletions (12%) of AXIN1 were detected. Baeza et al. (2003) screened 39 sporadic cerebellar medulloblastomas for alterations in the AXIN1 gene. The authors found missense AXIN1 mutations in two tumours, CCC-->TCC at codon 255 (exon 1, Pro-->Ser) and TCT-->TGT at codon 263 (exon 1, Ser-->Cys). Furthermore, the A allele at the G/A polymorphism at nucleotide 16 in intron 4 was significantly over-represented in medulloblastomas (39 cases; G 0.76 vs-A 0.24) compared to healthy individuals (86 cases; G 0.91 vs A 0.09; P=0.0027). Yokota et al. (2002) showed another AXIN1 mutation in exon 3, corresponding to GSK-3beta binding site.
  
Entity Colorectal carcinoma
Note Hart et al. (1998) report on overexpression of Axin1 in connection to the downregulation of wild-type beta-catenin in colon cancer cells. In addition, Axin1 dramatically facilitated the phosphorylation of APC and beta-catenin by GSK3 beta in vitro. Another group (Jin et al., 2003) analyzed 54 colorectal cancer tissues for mutations in AXIN1 gene. They found 3 silent mutations, 6 missense point mutations in different functionally important regions. The missense mutation rate was hence 11%, suggesting that Axin 1 deficiency may contribute to the onset of colorectal tumorigenesis. Segditsas and Tomlinson (2006) report on mutations in AXIN1 in microsatellite-unstable colon cancers. Three AXIN1 missense variants P312T, R398H, and L445M were detected in 1 of 124 patients with multiple colorectal adenomas. Three other missense mutations, D545E, G700S, and R891Q, were found. The overall frequency of the rare variants was significantly higher in the patients as compared with the controls (Fearnhead et al., 2004).
  
Entity Brain tumors
Note A sample of 72 neuroepithelial brain tumors was investigated for AXIN-1 gene changes by Nikuseva Martic et al. (2010). Polymorphic marker for AXIN-1, showed loss of heterozygosity in 11.1% of tumors. Down regulation of axin expression and up regulation of beta-catenin were detected. Axin was observed in the cytoplasm in 68.8% of samples, in 28.1% in both the cytoplasm and nucleus and 3.1% had no expression. Comparison of mean values of relative increase of axin and beta-catenin showed that they were significantly reversely proportional (P=0.014) in a set of neuroepithelial brain tumors. Pecina-Slaus et al. (2011) also explored axin's existence at the subcellular level in glioblastomas and showed that the highest relative quantity of axin was measured when the protein was in the nucleus and the lowest relative quantity of axin when the protein was localized in the cytoplasm.
  
Entity Ovarian endometroid adenocarcinomas
Note Wu et al. (2001) report on a nonsense mutation in one ovarian endometroid adenocarcinoma (OEA). They also found another missense AXIN1 sequence alteration in OEA-derived cell lines.
  
Entity Lung cancer
Note In 105 lung SCC and adenocarcinoma tissue samples, the cytoplasmic expression of Axin was significantly lower than in normal lung tissues. Western blot analysis also demonstrated that the relative expression quantity of Axin was significantly reduced in lung cancer tissues compared with normal lung tissues. Nuclear expression of Axin was observed in 21 cases (20%) of lung cancers (Xu et al., 2011).
  
Entity Oesophageal squamous cell carcinoma
Note Nakajima et al. (2003) found reduced expression of Axin1 in oesophageal squamous cell carcinoma. Several mutations have also been reported in oesophageal squamous cell carcinoma.
  
Entity Cervical cancer
Note Su et al. (2003) examined AXIN1 in cervical cancer. Among the 30 tested cervical cancers mutation analysis of AXIN1 revealed that one specimen had a heterozygous mutation at codon 740. Six polymorphisms were also found. Immunohistochemistry showed no relationship between the protein expression patterns and mutation of AXIN1.
  
Entity Prostate cancer
Note Yardy et al. (2009) reported on AXIN1 mutations in advanced prostate cancer. They found 7 mutations in prostate cancer cases and 4 polymorphisms in prostate cancer cell lines.
  
Entity Caudal duplication anomaly
Note Hypermethylation of the AXIN1 promoter is associated with the caudal duplication anomalies. Oates et al. (2006) examined methylation at the promoter region of the AXIN1 gene in monozygotic twins. The promoter region of the AXIN1 gene was significantly more methylated in the twin with the caudal duplication than in the unaffected twin.
  

Other Solid tumors implicated (Data extracted from papers in the Atlas)

Solid Tumors ProstateOverviewID5041

External links

Nomenclature
HGNC (Hugo)AXIN1   903
Cards
AtlasAXIN1ID379ch16p13
Entrez_Gene (NCBI)AXIN1  8312  axin 1
GeneCards (Weizmann)AXIN1
Ensembl (Hinxton)ENSG00000103126 [Gene_View]  chr16:337440-402676 [Contig_View]  AXIN1 [Vega]
ICGC DataPortalENSG00000103126
cBioPortalAXIN1
AceView (NCBI)AXIN1
Genatlas (Paris)AXIN1
WikiGenes8312
SOURCE (Princeton)NM_003502 NM_181050
Genomic and cartography
GoldenPath (UCSC)AXIN1  -  16p13.3   chr16:337440-402676 -  16p13.3   [Description]    (hg19-Feb_2009)
EnsemblAXIN1 - 16p13.3 [CytoView]
Mapping of homologs : NCBIAXIN1 [Mapview]
OMIM114550   603816   607864   
Gene and transcription
Genbank (Entrez)AB208876 AF009674 BC017447 BC035872 BC044648
RefSeq transcript (Entrez)NM_003502 NM_181050
RefSeq genomic (Entrez)AC_000148 NC_000016 NC_018927 NG_012267 NT_010393 NW_001838339 NW_004929400
Consensus coding sequences : CCDS (NCBI)AXIN1
Cluster EST : UnigeneHs.592082 [ NCBI ]
CGAP (NCI)Hs.592082
Alternative Splicing : Fast-db (Paris)GSHG0011489
Alternative Splicing GalleryENSG00000103126
Gene ExpressionAXIN1 [ NCBI-GEO ]     AXIN1 [ SEEK ]   AXIN1 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtO15169 (Uniprot)
NextProtO15169  [Medical]
With graphics : InterProO15169
Splice isoforms : SwissVarO15169 (Swissvar)
Domaine pattern : Prosite (Expaxy)DIX (PS50841)    RGS (PS50132)   
Domains : Interpro (EBI)Axin_b-cat-bd [organisation]   DIX [organisation]   Regulat_G_prot_signal_dom1 [organisation]   Regulat_G_prot_signal_superfam [organisation]   RGS_dom [organisation]  
Related proteins : CluSTrO15169
Domain families : Pfam (Sanger)Axin_b-cat_bind (PF08833)    DIX (PF00778)    RGS (PF00615)   
Domain families : Pfam (NCBI)pfam08833    pfam00778    pfam00615   
Domain families : Smart (EMBL)DAX (SM00021)  RGS (SM00315)  
DMDM Disease mutations8312
Blocks (Seattle)O15169
PDB (SRS)1DK8    1EMU    1O9U    3ZDI    4B7T   
PDB (PDBSum)1DK8    1EMU    1O9U    3ZDI    4B7T   
PDB (IMB)1DK8    1EMU    1O9U    3ZDI    4B7T   
PDB (RSDB)1DK8    1EMU    1O9U    3ZDI    4B7T   
Human Protein AtlasENSG00000103126 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasO15169
HPRD04819
IPIIPI00747002   IPI00748214   IPI00889758   
Protein Interaction databases
DIP (DOE-UCLA)O15169
IntAct (EBI)O15169
FunCoupENSG00000103126
BioGRIDAXIN1
InParanoidO15169
Interologous Interaction database O15169
IntegromeDBAXIN1
STRING (EMBL)AXIN1
Ontologies - Pathways
Ontology : AmiGOprotein polyubiquitination  in utero embryonic development  optic placode formation  positive regulation of protein phosphorylation  signal transducer activity  GTPase activator activity  protein binding  nucleus  cytoplasm  cytosol  cytoplasmic microtubule  cell cortex  nucleocytoplasmic transport  apoptotic process  activation of JUN kinase activity  determination of left/right symmetry  sensory perception of sound  beta-catenin binding  protein C-terminus binding  cell death  dorsal/ventral axis specification  positive regulation of peptidyl-threonine phosphorylation  postsynaptic density  cytoplasmic membrane-bounded vesicle  lateral plasma membrane  enzyme binding  protein kinase binding  protein kinase binding  forebrain anterior/posterior pattern specification  Wnt receptor signaling pathway involved in forebrain neuron fate commitment  protein catabolic process  negative regulation of Wnt receptor signaling pathway  positive regulation of transforming growth factor beta receptor signaling pathway  beta-catenin destruction complex  olfactory placode formation  cytoplasmic microtubule organization  positive regulation of protein ubiquitination  cytoplasmic vesicle  ubiquitin protein ligase binding  activation of protein kinase activity  positive regulation of proteasomal ubiquitin-dependent protein catabolic process  protein complex scaffold  protein complex scaffold  positive regulation of peptidyl-serine phosphorylation  negative regulation of transcription elongation from RNA polymerase II promoter  regulation of catenin import into nucleus  post-anal tail morphogenesis  termination of G-protein coupled receptor signaling pathway  identical protein binding  protein homodimerization activity  positive regulation of GTPase activity  protein self-association  cellular protein complex assembly  negative regulation of fat cell differentiation  positive regulation of protein catabolic process  positive regulation of protein catabolic process  positive regulation of transcription, DNA-dependent  positive regulation of JNK cascade  SMAD binding  embryonic eye morphogenesis  axial mesoderm formation  perinuclear region of cytoplasm  negative regulation of protein metabolic process  protein homooligomerization  positive regulation of ubiquitin-protein ligase activity  muscle cell development  canonical Wnt receptor signaling pathway  embryonic skeletal joint morphogenesis  canonical Wnt receptor signaling pathway involved in neural plate anterior/posterior pattern formation  armadillo repeat domain binding  armadillo repeat domain binding  I-SMAD binding  R-SMAD binding  cellular response to organic cyclic compound  genetic imprinting  cell periphery  negative regulation of canonical Wnt receptor signaling pathway  Wnt receptor signaling pathway involved in somitogenesis  positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process  
Ontology : EGO-EBIprotein polyubiquitination  in utero embryonic development  optic placode formation  positive regulation of protein phosphorylation  signal transducer activity  GTPase activator activity  protein binding  nucleus  cytoplasm  cytosol  cytoplasmic microtubule  cell cortex  nucleocytoplasmic transport  apoptotic process  activation of JUN kinase activity  determination of left/right symmetry  sensory perception of sound  beta-catenin binding  protein C-terminus binding  cell death  dorsal/ventral axis specification  positive regulation of peptidyl-threonine phosphorylation  postsynaptic density  cytoplasmic membrane-bounded vesicle  lateral plasma membrane  enzyme binding  protein kinase binding  protein kinase binding  forebrain anterior/posterior pattern specification  Wnt receptor signaling pathway involved in forebrain neuron fate commitment  protein catabolic process  negative regulation of Wnt receptor signaling pathway  positive regulation of transforming growth factor beta receptor signaling pathway  beta-catenin destruction complex  olfactory placode formation  cytoplasmic microtubule organization  positive regulation of protein ubiquitination  cytoplasmic vesicle  ubiquitin protein ligase binding  activation of protein kinase activity  positive regulation of proteasomal ubiquitin-dependent protein catabolic process  protein complex scaffold  protein complex scaffold  positive regulation of peptidyl-serine phosphorylation  negative regulation of transcription elongation from RNA polymerase II promoter  regulation of catenin import into nucleus  post-anal tail morphogenesis  termination of G-protein coupled receptor signaling pathway  identical protein binding  protein homodimerization activity  positive regulation of GTPase activity  protein self-association  cellular protein complex assembly  negative regulation of fat cell differentiation  positive regulation of protein catabolic process  positive regulation of protein catabolic process  positive regulation of transcription, DNA-dependent  positive regulation of JNK cascade  SMAD binding  embryonic eye morphogenesis  axial mesoderm formation  perinuclear region of cytoplasm  negative regulation of protein metabolic process  protein homooligomerization  positive regulation of ubiquitin-protein ligase activity  muscle cell development  canonical Wnt receptor signaling pathway  embryonic skeletal joint morphogenesis  canonical Wnt receptor signaling pathway involved in neural plate anterior/posterior pattern formation  armadillo repeat domain binding  armadillo repeat domain binding  I-SMAD binding  R-SMAD binding  cellular response to organic cyclic compound  genetic imprinting  cell periphery  negative regulation of canonical Wnt receptor signaling pathway  Wnt receptor signaling pathway involved in somitogenesis  positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process  
Pathways : BIOCARTAALK in cardiac myocytes [Genes]    Presenilin action in Notch and Wnt signaling [Genes]    Inactivation of Gsk3 by AKT causes accumulation of b-catenin in Alveolar Macrophages [Genes]    WNT Signaling Pathway [Genes]    Multi-step Regulation of Transcription by Pitx2 [Genes]   
Pathways : KEGGWnt signaling pathway    Hippo signaling pathway    Pathways in cancer    Colorectal cancer    Endometrial cancer    Basal cell carcinoma   
Protein Interaction DatabaseAXIN1
Wikipedia pathwaysAXIN1
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)AXIN1
snp3D : Map Gene to Disease8312
SNP (GeneSNP Utah)AXIN1
SNP : HGBaseAXIN1
Genetic variants : HAPMAPAXIN1
Exome VariantAXIN1
1000_GenomesAXIN1 
ICGC programENSG00000103126 
Cancer Gene: CensusAXIN1 
Somatic Mutations in Cancer : COSMICAXIN1 
CONAN: Copy Number AnalysisAXIN1 
Mutations and Diseases : HGMDAXIN1
Genomic VariantsAXIN1  AXIN1 [DGVbeta]
dbVarAXIN1
ClinVarAXIN1
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM114550    603816    607864   
MedgenAXIN1
GENETestsAXIN1
Disease Genetic AssociationAXIN1
Huge Navigator AXIN1 [HugePedia]  AXIN1 [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneAXIN1
Homology/Alignments : Family Browser (UCSC)AXIN1
Phylogenetic Trees/Animal Genes : TreeFamAXIN1
Chemical/Protein Interactions : CTD8312
Chemical/Pharm GKB GenePA25195
Clinical trialAXIN1
Cancer Resource (Charite)ENSG00000103126
Other databases
Other databaseThe Wnt Homepage
Probes
Litterature
PubMed152 Pubmed reference(s) in Entrez
CoreMineAXIN1
iHOPAXIN1

Bibliography

The mouse Fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation.
Zeng L, Fagotto F, Zhang T, Hsu W, Vasicek TJ, Perry WL 3rd, Lee JJ, Tilghman SM, Gumbiner BM, Costantini F.
Cell. 1997 Jul 11;90(1):181-92.
PMID 9230313
 
Downregulation of beta-catenin by human Axin and its association with the APC tumor suppressor, beta-catenin and GSK3 beta.
Hart MJ, de los Santos R, Albert IN, Rubinfeld B, Polakis P.
Curr Biol. 1998 May 7;8(10):573-81.
PMID 9601641
 
Mechanisms of Wnt signaling in development.
Wodarz A, Nusse R.
Annu Rev Cell Dev Biol. 1998;14:59-88. (REVIEW)
PMID 9891778
 
Phosphorylation of axin, a Wnt signal negative regulator, by glycogen synthase kinase-3beta regulates its stability.
Yamamoto H, Kishida S, Kishida M, Ikeda S, Takada S, Kikuchi A.
J Biol Chem. 1999 Apr 16;274(16):10681-4.
PMID 10196136
 
Wnt signaling and cancer.
Polakis P.
Genes Dev. 2000 Aug 1;14(15):1837-51. (REVIEW)
PMID 10921899
 
AXIN1 mutations in hepatocellular carcinomas, and growth suppression in cancer cells by virus-mediated transfer of AXIN1.
Satoh S, Daigo Y, Furukawa Y, Kato T, Miwa N, Nishiwaki T, Kawasoe T, Ishiguro H, Fujita M, Tokino T, Sasaki Y, Imaoka S, Murata M, Shimano T, Yamaoka Y, Nakamura Y.
Nat Genet. 2000 Mar;24(3):245-50.
PMID 10700176
 
Deletions of AXIN1, a component of the WNT/wingless pathway, in sporadic medulloblastomas.
Dahmen RP, Koch A, Denkhaus D, Tonn JC, Sorensen N, Berthold F, Behrens J, Birchmeier W, Wiestler OD, Pietsch T.
Cancer Res. 2001 Oct 1;61(19):7039-43.
PMID 11585731
 
Axin facilitates Smad3 activation in the transforming growth factor beta signaling pathway.
Furuhashi M, Yagi K, Yamamoto H, Furukawa Y, Shimada S, Nakamura Y, Kikuchi A, Miyazono K, Kato M.
Mol Cell Biol. 2001 Aug;21(15):5132-41.
PMID 11438668
 
Diverse mechanisms of beta-catenin deregulation in ovarian endometrioid adenocarcinomas.
Wu R, Zhai Y, Fearon ER, Cho KR.
Cancer Res. 2001 Nov 15;61(22):8247-55.
PMID 11719457
 
Subcellular distribution of Wnt pathway proteins in normal and neoplastic colon.
Anderson CB, Neufeld KL, White RL.
Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8683-8. Epub 2002 Jun 18.
PMID 12072559
 
Mutational spectrum of beta-catenin, AXIN1, and AXIN2 in hepatocellular carcinomas and hepatoblastomas.
Taniguchi K, Roberts LR, Aderca IN, Dong X, Qian C, Murphy LM, Nagorney DM, Burgart LJ, Roche PC, Smith DI, Ross JA, Liu W.
Oncogene. 2002 Jul 18;21(31):4863-71.
PMID 12101426
 
Role of Wnt pathway in medulloblastoma oncogenesis.
Yokota N, Nishizawa S, Ohta S, Date H, Sugimura H, Namba H, Maekawa M.
Int J Cancer. 2002 Sep 10;101(2):198-201.
PMID 12209999
 
AXIN1 mutations but not deletions in cerebellar medulloblastomas.
Baeza N, Masuoka J, Kleihues P, Ohgaki H.
Oncogene. 2003 Jan 30;22(4):632-6.
PMID 12555076
 
A role of Dishevelled in relocating Axin to the plasma membrane during wingless signaling.
Cliffe A, Hamada F, Bienz M.
Curr Biol. 2003 May 27;13(11):960-6.
PMID 12781135
 
Detection of point mutations of the Axin1 gene in colorectal cancers.
Jin LH, Shao QJ, Luo W, Ye ZY, Li Q, Lin SC.
Int J Cancer. 2003 Dec 10;107(5):696-9.
PMID 14566817
 
Reduced expression of Axin correlates with tumour progression of oesophageal squamous cell carcinoma.
Nakajima M, Fukuchi M, Miyazaki T, Masuda N, Kato H, Kuwano H.
Br J Cancer. 2003 Jun 2;88(11):1734-9.
PMID 12771989
 
A role for Wnt signalling in self-renewal of haematopoietic stem cells.
Reya T, Duncan AW, Ailles L, Domen J, Scherer DC, Willert K, Hintz L, Nusse R, Weissman IL.
Nature. 2003 May 22;423(6938):409-14. Epub 2003 Apr 27.
PMID 12717450
 
Mutation analysis of CTNNB1 (beta-catenin) and AXIN1, the components of Wnt pathway, in cervical carcinomas.
Su TH, Chang JG, Yeh KT, Lin TH, Lee TP, Chen JC, Lin CC.
Oncol Rep. 2003 Sep-Oct;10(5):1195-200.
PMID 12883680
 
Nuclear-cytoplasmic shuttling of Axin regulates subcellular localization of beta-catenin.
Cong F, Varmus H.
Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):2882-7. Epub 2004 Feb 23.
PMID 14981260
 
Multiple rare variants in different genes account for multifactorial inherited susceptibility to colorectal adenomas.
Fearnhead NS, Wilding JL, Winney B, Tonks S, Bartlett S, Bicknell DC, Tomlinson IP, Mortensen NJ, Bodmer WF.
Proc Natl Acad Sci U S A. 2004 Nov 9;101(45):15992-7. Epub 2004 Nov 1.
PMID 15520370
 
The Wnt signaling pathway in development and disease.
Logan CY, Nusse R.
Annu Rev Cell Dev Biol. 2004;20:781-810. (REVIEW)
PMID 15473860
 
Axin: a master scaffold for multiple signaling pathways.
Luo W, Lin SC.
Neurosignals. 2004 May-Jun;13(3):99-113. (REVIEW)
PMID 15067197
 
Nucleo-cytoplasmic shuttling of Axin, a negative regulator of the Wnt-beta-catenin Pathway.
Wiechens N, Heinle K, Englmeier L, Schohl A, Fagotto F.
J Biol Chem. 2004 Feb 13;279(7):5263-7. Epub 2003 Nov 20.
PMID 14630927
 
Axin contains three separable domains that confer intramolecular, homodimeric, and heterodimeric interactions involved in distinct functions.
Luo W, Zou H, Jin L, Lin S, Li Q, Ye Z, Rui H, Lin SC.
J Biol Chem. 2005 Feb 11;280(6):5054-60. Epub 2004 Dec 5.
PMID 15579909
 
Mutations of beta-catenin and AXIN I genes are a late event in human hepatocellular carcinogenesis.
Park JY, Park WS, Nam SW, Kim SY, Lee SH, Yoo NJ, Lee JY, Park CK.
Liver Int. 2005 Feb;25(1):70-6.
PMID 15698401
 
The links between axin and carcinogenesis.
Salahshor S, Woodgett JR.
J Clin Pathol. 2005 Mar;58(3):225-36. (REVIEW)
PMID 15735151
 
Increased DNA methylation at the AXIN1 gene in a monozygotic twin from a pair discordant for a caudal duplication anomaly.
Oates NA, van Vliet J, Duffy DL, Kroes HY, Martin NG, Boomsma DI, Campbell M, Coulthard MG, Whitelaw E, Chong S.
Am J Hum Genet. 2006 Jul;79(1):155-62. Epub 2006 May 22.
PMID 16773576
 
Colorectal cancer and genetic alterations in the Wnt pathway.
Segditsas S, Tomlinson I.
Oncogene. 2006 Dec 4;25(57):7531-7. (REVIEW)
PMID 17143297
 
Crystallization and preliminary X-ray crystallographic studies of the axin DIX domain.
Shibata N, Tomimoto Y, Hanamura T, Yamamoto R, Ueda M, Ueda Y, Mizuno N, Ogata H, Komori H, Shomura Y, Kataoka M, Shimizu S, Kondo J, Yamamoto H, Kikuchi A, Higuchi Y.
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2007 Jun 1;63(Pt 6):529-31. Epub 2007 May 18.
PMID 17554179
 
SUMOylation target sites at the C terminus protect Axin from ubiquitination and confer protein stability.
Kim MJ, Chia IV, Costantini F.
FASEB J. 2008 Nov;22(11):3785-94. Epub 2008 Jul 16.
PMID 18632848
 
Identification of zinc-finger BED domain-containing 3 (Zbed3) as a novel Axin-interacting protein that activates Wnt/beta-catenin signaling.
Chen T, Li M, Ding Y, Zhang LS, Xi Y, Pan WJ, Tao DL, Wang JY, Li L.
J Biol Chem. 2009 Mar 13;284(11):6683-9. Epub 2009 Jan 13.
PMID 19141611
 
The structural and functional determinants of the Axin and Dishevelled DIX domains.
Ehebauer MT, Arias AM.
BMC Struct Biol. 2009 Nov 12;9:70.
PMID 19909509
 
Axin localizes to the centrosome and is involved in microtubule nucleation.
Fumoto K, Kadono M, Izumi N, Kikuchi A.
EMBO Rep. 2009 Jun;10(6):606-13. Epub 2009 Apr 24.
PMID 19390532
 
Axin determines cell fate by controlling the p53 activation threshold after DNA damage.
Li Q, Lin S, Wang X, Lian G, Lu Z, Guo H, Ruan K, Wang Y, Ye Z, Han J, Lin SC.
Nat Cell Biol. 2009 Sep;11(9):1128-34.
PMID 19731416
 
Identification of WNT/beta-CATENIN signaling pathway components in human cumulus cells.
Wang HX, Tekpetey FR, Kidder GM.
Mol Hum Reprod. 2009 Jan;15(1):11-7. Epub 2008 Nov 26.
PMID 19038973
 
Mutations in the AXIN1 gene in advanced prostate cancer.
Yardy GW, Bicknell DC, Wilding JL, Bartlett S, Liu Y, Winney B, Turner GD, Brewster SF, Bodmer WF.
Eur Urol. 2009 Sep;56(3):486-94. Epub 2008 May 23.
PMID 18514389
 
Coexpression and protein-protein complexing of DIX domains of human Dvl1 and Axin1 protein.
Choi SH, Choi KM, Ahn HJ.
BMB Rep. 2010 Sep;43(9):609-13.
PMID 20846493
 
The protein stability of Axin, a negative regulator of Wnt signaling, is regulated by Smad ubiquitination regulatory factor 2 (Smurf2).
Kim S, Jho EH.
J Biol Chem. 2010 Nov 19;285(47):36420-6. Epub 2010 Sep 21.
PMID 20858899
 
Changes of AXIN-1 and beta-catenin in neuroepithelial brain tumors.
Nikuseva Martic T, Pecina-Slaus N, Kusec V, Kokotovic T, Musinovic H, Tomas D, Zeljko M.
Pathol Oncol Res. 2010 Mar;16(1):75-9. Epub 2009 Jul 25.
PMID 19633924
 
Wnt signal transduction pathway and apoptosis: a review.
Pecina-Slaus N.
Cancer Cell Int. 2010 Jun 30;10:22.
PMID 20591184
 
Critical scaffolding regions of the tumor suppressor Axin1 are natively unfolded.
Noutsou M, Duarte AM, Anvarian Z, Didenko T, Minde DP, Kuper I, de Ridder I, Oikonomou C, Friedler A, Boelens R, Rudiger SG, Maurice MM.
J Mol Biol. 2011 Jan 21;405(3):773-86. Epub 2010 Nov 16.
PMID 21087614
 
AXIN-1 protein expression and localization in glioblastoma.
Pecina-Slaus N, Martic TN, Kokotovic T, Kusec V, Tomas D, Hrascan R.
Coll Antropol. 2011 Jan;35 Suppl 1:101-6.
PMID 21648318
 
Disabled-2 and Axin are concurrently colocalized and underexpressed in lung cancers.
Xu HT, Yang LH, Li QC, Liu SL, Liu D, Xie XM, Wang EH.
Hum Pathol. 2011 Apr 13. [Epub ahead of print]
PMID 21496867
 
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Contributor(s)

Written05-2011Nives Pecina-Slaus, Tamara Nikuseva Martic, Tomislav Kokotovic
Department of Biology, Laboratory for Neurooncology, Croatian Institute for Brain Research, Medical School University of Zagreb, Salata 12, Zagreb, Croatia

Citation

This paper should be referenced as such :
Pecina-Slaus, N ; Nikuseva, Martic T ; Kokotovic, T
AXIN1 (axin 1)
Atlas Genet Cytogenet Oncol Haematol. 2011;15(11):933-937.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/AXIN1ID379ch16p13.html

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