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Gene Review

AXIN1  -  axin 1

Homo sapiens

Synonyms: AXIN, Axin-1, Axis inhibition protein 1, PPP1R49, hAxin
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Disease relevance of AXIN1


High impact information on AXIN1


Chemical compound and disease context of AXIN1

  • A polyhistidine-tagged axin peptide (residues 419-672) was produced in Escherichia coli and either immobilized on Ni-NTA agarose beads or purified and immobilized on CNBr-activated Sepharose 4B [11].

Biological context of AXIN1

  • 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 [2].
  • This indicates that AXIN1 may function as a tumor suppressor gene in MBs [2].
  • In the remaining 29 primary OEAs, unequivocal nuclear beta-catenin immunoreactivity was not observed, though a nonsense mutation in AXIN1 was observed in one tumor and a truncating frameshift mutation in AXIN2 was seen in another case [12].
  • 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 [13].
  • The AXIN1 mutations included seven missense mutations, a 1 bp deletion, and a 12 bp insertion [13].

Anatomical context of AXIN1

  • Among the 4 cell lines and 87 HCC5 in which we did not detect CTNNB1 mutations, we identified AXIN1 mutations in 3 cell lines and 6 mutations in 5 of the primary HCCs [1].
  • Constitutive activation of the Wnt signaling pathway as a result of genetic alterations of APC, AXIN1, and CTNNB1 has been found in various human cancers, including those of the colon, liver, endometrium, ovary, prostate, and stomach [14].
  • Furthermore, Axin stimulated the degradation of beta-catenin in COS cells [15].
  • Based on these observations, Axin was screened for mutations in a range of human tumor cell lines and primary breast tumor samples [16].
  • Wnt11/{beta}-catenin signaling in both oocytes and early embryos acts through LRP6-mediated regulation of axin [17].

Associations of AXIN1 with chemical compounds

  • Using bisulfite sequencing, we examined methylation at the promoter region of the AXIN1 gene in these twins and in twin and age-matched singleton controls [18].
  • Mutation of LRP6 Ser(1420) and Ser(1430) to alanine strengthens its interaction with axin, suggesting a mechanism by which CKIepsilon may negatively regulate Wnt signaling [19].

Physical interactions of AXIN1


Co-localisations of AXIN1

  • In the absence of ligand stimulation, Axin was colocalized with Smad3 in the cytoplasm in vivo [20].

Regulatory relationships of AXIN1

  • Axin down-regulated beta-catenin in SW480 cells, but not Axin(delta)(beta)(-catenin) [25].
  • Adenomatous polyposis coli is down-regulated by the ubiquitin-proteasome pathway in a process facilitated by Axin [26].
  • These results suggest that p53 induces a faster mobilization of Axin into the degradation complex thereby enhancing beta-catenin turnover as part of a protective mechanism against the development of cancer [27].
  • In the full-grown oocyte, before maturation, we find that axin levels are also regulated by Wnt11 and LRP6 [17].
  • This suggests that even when Axin is "switched" to activate the JNK pathway, it is still capable of sequestering free beta-catenin, which is a critical aspect for cellular homeostasis [28].

Other interactions of AXIN1


Analytical, diagnostic and therapeutic context of AXIN1

  • Since there are multiple complementary, inverted sequences present in the AXIN1 gene, these large deletions may represent RT-PCR errors due to stem-loop secondary structures [31].
  • AXIN1 protein immunohistochemistry revealed cytoplasmic expression in all tumours irrespective of the presence of AXIN1 locus LOH [5].
  • Purification of GSK-3 by affinity chromatography on immobilized axin [11].
  • By means of a cDNA microarray, we compared expression profiles of LoVo cells infected with either adenoviruses expressing wild-type AXIN1 (Ad-Axin) or those expressing a control gene (Ad-LacZ) [32].
  • We employed PCR amplification with 23 sets of primers against introns that encompassed the whole coding region of AXIN1 followed by single-strand conformation polymorphism (SSCP) analysis [33].


  1. 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) [Pubmed]
  2. Deletions of AXIN1, a component of the WNT/wingless pathway, in sporadic medulloblastomas. Dahmen, R.P., Koch, A., Denkhaus, D., Tonn, J.C., Sörensen, N., Berthold, F., Behrens, J., Birchmeier, W., Wiestler, O.D., Pietsch, T. Cancer Res. (2001) [Pubmed]
  3. Colorectal cancer and genetic alterations in the Wnt pathway. Segditsas, S., Tomlinson, I. Oncogene (2006) [Pubmed]
  4. Identification of AXUD1, a novel human gene induced by AXIN1 and its reduced expression in human carcinomas of the lung, liver, colon and kidney. Ishiguro, H., Tsunoda, T., Tanaka, T., Fujii, Y., Nakamura, Y., Furukawa, Y. Oncogene (2001) [Pubmed]
  5. Frequent loss of the AXIN1 locus but absence of AXIN1 gene mutations in adenocarcinomas of the gastro-oesophageal junction with nuclear beta-catenin expression. Koppert, L.B., van der Velden, A.W., van de Wetering, M., Abbou, M., van den Ouweland, A.M., Tilanus, H.W., Wijnhoven, B.P., Dinjens, W.N. Br. J. Cancer (2004) [Pubmed]
  6. P68 RNA Helicase Mediates PDGF-Induced Epithelial Mesenchymal Transition by Displacing Axin from beta-Catenin. Yang, L., Lin, C., Liu, Z.R. Cell (2006) [Pubmed]
  7. A human protein-protein interaction network: a resource for annotating the proteome. Stelzl, U., Worm, U., Lalowski, M., Haenig, C., Brembeck, F.H., Goehler, H., Stroedicke, M., Zenkner, M., Schoenherr, A., Koeppen, S., Timm, J., Mintzlaff, S., Abraham, C., Bock, N., Kietzmann, S., Goedde, A., Toksöz, E., Droege, A., Krobitsch, S., Korn, B., Birchmeier, W., Lehrach, H., Wanker, E.E. Cell (2005) [Pubmed]
  8. Wnt-induced dephosphorylation of axin releases beta-catenin from the axin complex. Willert, K., Shibamoto, S., Nusse, R. Genes Dev. (1999) [Pubmed]
  9. Genetic alterations associated with hepatocellular carcinomas define distinct pathways of hepatocarcinogenesis. Laurent-Puig, P., Legoix, P., Bluteau, O., Belghiti, J., Franco, D., Binot, F., Monges, G., Thomas, G., Bioulac-Sage, P., Zucman-Rossi, J. Gastroenterology (2001) [Pubmed]
  10. Axin is a scaffold protein in TGF-beta signaling that promotes degradation of Smad7 by Arkadia. Liu, W., Rui, H., Wang, J., Lin, S., He, Y., Chen, M., Li, Q., Ye, Z., Zhang, S., Chan, S.C., Chen, Y.G., Han, J., Lin, S.C. EMBO J. (2006) [Pubmed]
  11. Purification of GSK-3 by affinity chromatography on immobilized axin. Primot, A., Baratte, B., Gompel, M., Borgne, A., Liabeuf, S., Romette, J.L., Jho, E.H., Costantini, F., Meijer, L. Protein Expr. Purif. (2000) [Pubmed]
  12. Diverse mechanisms of beta-catenin deregulation in ovarian endometrioid adenocarcinomas. Wu, R., Zhai, Y., Fearon, E.R., Cho, K.R. Cancer Res. (2001) [Pubmed]
  13. Mutational spectrum of beta-catenin, AXIN1, and AXIN2 in hepatocellular carcinomas and hepatoblastomas. Taniguchi, K., Roberts, L.R., Aderca, I.N., Dong, X., Qian, C., Murphy, L.M., Nagorney, D.M., Burgart, L.J., Roche, P.C., Smith, D.I., Ross, J.A., Liu, W. Oncogene (2002) [Pubmed]
  14. Constitutive activation of the Wnt signaling pathway by CTNNB1 (beta-catenin) mutations in a subset of human lung adenocarcinoma. Sunaga, N., Kohno, T., Kolligs, F.T., Fearon, E.R., Saito, R., Yokota, J. Genes Chromosomes Cancer (2001) [Pubmed]
  15. Axin, a negative regulator of the wnt signaling pathway, directly interacts with adenomatous polyposis coli and regulates the stabilization of beta-catenin. Kishida, S., Yamamoto, H., Ikeda, S., Kishida, M., Sakamoto, I., Koyama, S., Kikuchi, A. J. Biol. Chem. (1998) [Pubmed]
  16. Sequence variants of the axin gene in breast, colon, and other cancers: an analysis of mutations that interfere with GSK3 binding. Webster, M.T., Rozycka, M., Sara, E., Davis, E., Smalley, M., Young, N., Dale, T.C., Wooster, R. Genes Chromosomes Cancer (2000) [Pubmed]
  17. Wnt11/{beta}-catenin signaling in both oocytes and early embryos acts through LRP6-mediated regulation of axin. Kofron, M., Birsoy, B., Houston, D., Tao, Q., Wylie, C., Heasman, J. Development (2007) [Pubmed]
  18. Increased DNA methylation at the AXIN1 gene in a monozygotic twin from a pair discordant for a caudal duplication anomaly. Oates, N.A., van Vliet, J., Duffy, D.L., Kroes, H.Y., Martin, N.G., Boomsma, D.I., Campbell, M., Coulthard, M.G., Whitelaw, E., Chong, S. Am. J. Hum. Genet. (2006) [Pubmed]
  19. Negative Regulation of LRP6 Function by Casein Kinase I {epsilon} Phosphorylation. Swiatek, W., Kang, H., Garcia, B.A., Shabanowitz, J., Coombs, G.S., Hunt, D.F., Virshup, D.M. J. Biol. Chem. (2006) [Pubmed]
  20. 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) [Pubmed]
  21. Axin-dependent phosphorylation of the adenomatous polyposis coli protein mediated by casein kinase 1epsilon. Rubinfeld, B., Tice, D.A., Polakis, P. J. Biol. Chem. (2001) [Pubmed]
  22. IKKalpha stabilizes cytosolic beta-catenin by inhibiting both canonical and non-canonical degradation pathways. Carayol, N., Wang, C.Y. Cell. Signal. (2006) [Pubmed]
  23. The DIX domain protein coiled-coil-DIX1 inhibits c-Jun N-terminal kinase activation by Axin and dishevelled through distinct mechanisms. Wong, C.K., Luo, W., Deng, Y., Zou, H., Ye, Z., Lin, S.C. J. Biol. Chem. (2004) [Pubmed]
  24. The interaction between beta-catenin, GSK3beta and APC after motogen induced cell-cell dissociation, and their involvement in signal transduction pathways in prostate cancer. Davies, G., Jiang, W.G., Mason, M.D. Int. J. Oncol. (2001) [Pubmed]
  25. Complex formation of adenomatous polyposis coli gene product and axin facilitates glycogen synthase kinase-3 beta-dependent phosphorylation of beta-catenin and down-regulates beta-catenin. Hinoi, T., Yamamoto, H., Kishida, M., Takada, S., Kishida, S., Kikuchi, A. J. Biol. Chem. (2000) [Pubmed]
  26. Adenomatous polyposis coli is down-regulated by the ubiquitin-proteasome pathway in a process facilitated by Axin. Choi, J., Park, S.Y., Costantini, F., Jho, E.H., Joo, C.K. J. Biol. Chem. (2004) [Pubmed]
  27. Downregulation of beta-catenin by p53 involves changes in the rate of beta-catenin phosphorylation and Axin dynamics. Levina, E., Oren, M., Ben-Ze'ev, A. Oncogene (2004) [Pubmed]
  28. Differential molecular assemblies underlie the dual function of Axin in modulating the WNT and JNK pathways. Zhang, Y., Qiu, W.J., Liu, D.X., Neo, S.Y., He, X., Lin, S.C. J. Biol. Chem. (2001) [Pubmed]
  29. Dimerization choices control the ability of axin and dishevelled to activate c-Jun N-terminal kinase/stress-activated protein kinase. Zhang, Y., Neo, S.Y., Han, J., Lin, S.C. J. Biol. Chem. (2000) [Pubmed]
  30. Structural basis of the Axin-adenomatous polyposis coli interaction. Spink, K.E., Polakis, P., Weis, W.I. EMBO J. (2000) [Pubmed]
  31. AXIN1 mutations but not deletions in cerebellar medulloblastomas. Baeza, N., Masuoka, J., Kleihues, P., Ohgaki, H. Oncogene (2003) [Pubmed]
  32. Up-regulation of the ectodermal-neural cortex 1 (ENC1) gene, a downstream target of the beta-catenin/T-cell factor complex, in colorectal carcinomas. Fujita, M., Furukawa, Y., Tsunoda, T., Tanaka, T., Ogawa, M., Nakamura, Y. Cancer Res. (2001) [Pubmed]
  33. Detection of point mutations of the Axin1 gene in colorectal cancers. Jin, L.H., Shao, Q.J., Luo, W., Ye, Z.Y., Li, Q., Lin, S.C. Int. J. Cancer (2003) [Pubmed]
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