Axin

Summary

Gene Symbol: Axin
Description: axin 1
Alias: Axin, axin-1, axin-1, GSK-3beta interacting protein rAxin, axis inhibition protein 1, rAxin
Species: rat
Products:     Axin

Top Publications

  1. Ciani L, Krylova O, Smalley M, Dale T, Salinas P. A divergent canonical WNT-signaling pathway regulates microtubule dynamics: dishevelled signals locally to stabilize microtubules. J Cell Biol. 2004;164:243-53 pubmed
    ..In the canonical WNT pathway, the negative regulator Axin forms a complex with beta-catenin and GSK-3beta, resulting in beta-catenin degradation...
  2. Ikeda S, Kishida S, Yamamoto H, Murai H, Koyama S, Kikuchi A. 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. EMBO J. 1998;17:1371-84 pubmed
    ..has been identified as a negative regulator of the Wnt signaling pathway; therefore, we termed this protein rAxin (rat Axin). rAxin interacted directly with, and was phosphorylated by, GSK-3beta...
  3. Zeng L, Fagotto F, Zhang T, Hsu W, Vasicek T, Perry W, et al. The mouse Fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation. Cell. 1997;90:181-92 pubmed
    ..The product of the Fused locus, Axin, displays similarities to RGS (Regulators of G-Protein Signaling) and Dishevelled proteins...
  4. Hsu W, Zeng L, Costantini F. Identification of a domain of Axin that binds to the serine/threonine protein phosphatase 2A and a self-binding domain. J Biol Chem. 1999;274:3439-45 pubmed
    b>Axin is a negative regulator of embryonic axis formation in vertebrates, which acts through a Wnt signal transduction pathway involving the serine/threonine kinase GSK-3 and beta-catenin...
  5. Zhang M, Liao Y, Lonnerdal B. EGR-1 is an active transcription factor in TGF-?2-mediated small intestinal cell differentiation. J Nutr Biochem. 2016;37:101-108 pubmed publisher
    ..The effect of TGF-?2 on maintaining small intestinal cell homeostasis was partially explained by Axin1 activation through EGR-1. ..
  6. Huang S, Mishina Y, Liu S, Cheung A, Stegmeier F, Michaud G, et al. Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Nature. 2009;461:614-20 pubmed publisher
    ..XAV939 stimulates beta-catenin degradation by stabilizing axin, the concentration-limiting component of the destruction complex...
  7. Kim S, Park C, Lee M, Kwon M, Jho E, Song W. Cyclin-dependent kinase 2 regulates the interaction of Axin with beta-catenin. Biochem Biophys Res Commun. 2004;317:478-83 pubmed
    b>Axin, a negative regulator of Wnt, forms a complex with glycogen synthase kinase 3beta, beta-catenin, and adenomatous polyposis coli and promotes GSK3beta-dependent phosphorylation of beta-catenin, thereby stimulating degradation of the ..
  8. Chen H, Lin C, Lin C, Perez Olle R, Leung C, Liem R. The role of microtubule actin cross-linking factor 1 (MACF1) in the Wnt signaling pathway. Genes Dev. 2006;20:1933-45 pubmed
    ..In the absence of Wnt, MACF1 associated with a complex that contained Axin, beta-catenin, GSK3beta, and APC...
  9. Ohshima R, Ohta T, Wu W, Koike A, Iwatani T, Henderson M, et al. Putative tumor suppressor EDD interacts with and up-regulates APC. Genes Cells. 2007;12:1339-45 pubmed
    ..Over-expression of EDD enhanced the protein expression level of APC and its binding partner Axin, resulting in inhibition of Wnt signaling downstream of beta-catenin...

More Information

Publications56

  1. Berwick D, Harvey K. LRRK2 functions as a Wnt signaling scaffold, bridging cytosolic proteins and membrane-localized LRP6. Hum Mol Genet. 2012;21:4966-79 pubmed publisher
    ..Finally, a newly developed LRRK2 kinase inhibitor disrupted Wnt signaling to a similar extent as pathogenic LRRK2 mutations. The use of LRRK2 kinase inhibition to treat PD may therefore need reconsideration. ..
  2. Xie R, Jiang R, Chen D. Generation of Axin1 conditional mutant mice. Genesis. 2011;49:98-102 pubmed publisher
    ..Thus, this Axin1(fx/fx) mouse model will be valuable for systematic tissue-specific dissection of the roles of Axin1 in embryonic and postnatal development and diseases. ..
  3. Kishida S, Yamamoto H, Hino S, Ikeda S, Kishida M, Kikuchi A. DIX domains of Dvl and axin are necessary for protein interactions and their ability to regulate beta-catenin stability. Mol Cell Biol. 1999;19:4414-22 pubmed
    The N-terminal region of Dvl-1 (a mammalian Dishevelled homolog) shares 37% identity with the C-terminal region of Axin, and this related region is named the DIX domain. The functions of the DIX domains of Dvl-1 and Axin were investigated...
  4. Tanneberger K, Pfister A, Brauburger K, Schneikert J, Hadjihannas M, Kriz V, et al. Amer1/WTX couples Wnt-induced formation of PtdIns(4,5)P2 to LRP6 phosphorylation. EMBO J. 2011;30:1433-43 pubmed publisher
    ..Knockdown of Amer1 reduces Wnt-induced LRP6 phosphorylation, Axin translocation to the plasma membrane and formation of LRP6 signalosomes...
  5. Hay E, Laplantine E, Geoffroy V, Frain M, Kohler T, Muller R, et al. N-cadherin interacts with axin and LRP5 to negatively regulate Wnt/beta-catenin signaling, osteoblast function, and bone formation. Mol Cell Biol. 2009;29:953-64 pubmed publisher
    ..demonstrate that N-cadherin, besides associating with beta-catenin at the membrane, forms a molecular complex with axin and LRP5 involving the LRP5 cytoplasmic tail domain...
  6. Reya T, Duncan A, Ailles L, Domen J, Scherer D, Willert K, et al. A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature. 2003;423:409-14 pubmed
    ..the physiological significance of this pathway for HSC proliferation we show that the ectopic expression of axin or a frizzled ligand-binding domain, inhibitors of the Wnt signalling pathway, leads to inhibition of HSC growth in ..
  7. Lu J, Zhang F, Yuan Y, Ding C, Zhang L, Li Q. All-trans retinoic acid upregulates the expression of p53 via Axin and inhibits the proliferation of glioma cells. Oncol Rep. 2013;29:2269-74 pubmed publisher
    ..In addition, ectopic expression of Axin by transient transfection of C6 cells with rAxin revealed that overexpression of Axin induced cell cycle arrest and apoptosis with an upregulation of p53...
  8. Schwarz Romond T, Fiedler M, Shibata N, Butler P, Kikuchi A, Higuchi Y, et al. The DIX domain of Dishevelled confers Wnt signaling by dynamic polymerization. Nat Struct Mol Biol. 2007;14:484-92 pubmed
    ..Dishevelled (Dvl) transduces the Wnt signal by interacting with the cytoplasmic Axin complex. Dvl and Axin each contain a DIX domain whose molecular properties and structure are unknown...
  9. Yamamoto H, Komekado H, Kikuchi A. Caveolin is necessary for Wnt-3a-dependent internalization of LRP6 and accumulation of beta-catenin. Dev Cell. 2006;11:213-23 pubmed
    ..single-span transmembrane Wnt receptor, low-density lipoprotein receptor-related protein 6 (LRP6), interacts with Axin to promote the Wnt-dependent accumulation of beta-catenin...
  10. Kim M, Chia I, Costantini F. SUMOylation target sites at the C terminus protect Axin from ubiquitination and confer protein stability. FASEB J. 2008;22:3785-94 pubmed publisher
    b>Axin is a scaffold protein for the beta-catenin destruction complex, and a negative regulator of canonical Wnt signaling...
  11. Karasawa T, Yokokura H, Kitajewski J, Lombroso P. Frizzled-9 is activated by Wnt-2 and functions in Wnt/beta -catenin signaling. J Biol Chem. 2002;277:37479-86 pubmed
    ..Rfz9 also relocalizes Axin from the cytoplasm to the plasma membrane in the presence of Dvl-1, suggesting that one of the consequences of Dvl-..
  12. Kishida M, Hino Si -, Michiue T, Yamamoto H, Kishida S, Fukui A, et al. Synergistic activation of the Wnt signaling pathway by Dvl and casein kinase Iepsilon. J Biol Chem. 2001;276:33147-55 pubmed
    ..In this study we show that CKIepsilon activates the Wnt signaling pathway in co-operation with Dvl. CKIepsilon and Axin associated with different sites of Dvl, and CKIepsilon and Dvl interacted with distinct regions on Axin...
  13. Ross S, Hemati N, Longo K, Bennett C, Lucas P, Erickson R, et al. Inhibition of adipogenesis by Wnt signaling. Science. 2000;289:950-3 pubmed
    ..When Wnt signaling in preadipocytes is prevented by overexpression of Axin or dominant-negative TCF4, these cells differentiate into adipocytes...
  14. Kitagawa M, Hatakeyama S, Shirane M, Matsumoto M, Ishida N, Hattori K, et al. An F-box protein, FWD1, mediates ubiquitin-dependent proteolysis of beta-catenin. EMBO J. 1999;18:2401-10 pubmed
    ..is preceded by phosphorylation of its N-terminal region by the glycogen synthase kinase-3beta (GSK-3beta)/Axin kinase complex...
  15. Grujic M, Christensen J, Sørensen M, Abrink M, Pejler G, Thomsen A. Delayed contraction of the CD8+ T cell response toward lymphocytic choriomeningitis virus infection in mice lacking serglycin. J Immunol. 2008;181:1043-51 pubmed
    ..In summary, the present report points to a novel, previously unrecognized role for serglycin proteoglycan in regulating the kinetics of antiviral CD8(+) T cell responses. ..
  16. Klaus A, Birchmeier W. Wnt signalling and its impact on development and cancer. Nat Rev Cancer. 2008;8:387-98 pubmed publisher
    ..Since then, further components of the Wnt pathway have been identified and their epistatic relationships have been defined. This article is a Timeline of crucial discoveries about the components and functions of this essential pathway. ..
  17. Rui Y, Xu Z, Lin S, Li Q, Rui H, Luo W, et al. Axin stimulates p53 functions by activation of HIPK2 kinase through multimeric complex formation. EMBO J. 2004;23:4583-94 pubmed
    b>Axin and p53 are tumor suppressors, controlling cell growth, apoptosis, and development...
  18. Lui T, Lacroix C, Ahmed S, Goldenberg S, Leach C, Daulat A, et al. The ubiquitin-specific protease USP34 regulates axin stability and Wnt/?-catenin signaling. Mol Cell Biol. 2011;31:2053-65 pubmed publisher
    ..Less is known, however, about the role of ubiquitin-specific proteases in Wnt signaling. Analysis of purified axin-containing protein complexes by liquid chromatography-tandem mass spectrometry revealed the presence of the ..
  19. Bilic J, Huang Y, Davidson G, Zimmermann T, Cruciat C, Bienz M, et al. Wnt induces LRP6 signalosomes and promotes dishevelled-dependent LRP6 phosphorylation. Science. 2007;316:1619-22 pubmed
    ..We propose that Wnts induce coclustering of receptors and Dvl in LRP6-signalosomes, which in turn triggers LRP6 phosphorylation to promote Axin recruitment and beta-catenin stabilization.
  20. Chia I, Kim M, Itoh K, Sokol S, Costantini F. Both the RGS domain and the six C-terminal amino acids of mouse Axin are required for normal embryogenesis. Genetics. 2009;181:1359-68 pubmed publisher
    b>Axin is a negative regulator of canonical Wnt signaling, which promotes the degradation of beta-catenin, the major effector in this signaling cascade...
  21. Cong F, Varmus H. Nuclear-cytoplasmic shuttling of Axin regulates subcellular localization of beta-catenin. Proc Natl Acad Sci U S A. 2004;101:2882-7 pubmed
    Wnt signaling regulates many aspects of development by increasing the signaling activity of beta-catenin. Axin is a negative regulator of the Wnt signaling pathway, and it is responsible for the formation of the beta-catenin degradation ..
  22. Penman G, Leung L, Nathke I. The adenomatous polyposis coli protein (APC) exists in two distinct soluble complexes with different functions. J Cell Sci. 2005;118:4741-50 pubmed
  23. Liu W, Rui H, Wang J, Lin S, He Y, Chen M, et al. Axin is a scaffold protein in TGF-beta signaling that promotes degradation of Smad7 by Arkadia. EMBO J. 2006;25:1646-58 pubmed
    ..Here, we show that Axin activates TGF-beta signaling by forming a multimeric complex consisting of Smad7 and ubiquitin E3 ligase Arkadia...
  24. Zhang Y, Liu S, Mickanin C, Feng Y, Charlat O, Michaud G, et al. RNF146 is a poly(ADP-ribose)-directed E3 ligase that regulates axin degradation and Wnt signalling. Nat Cell Biol. 2011;13:623-9 pubmed publisher
    ..b>Axin is a concentration-limiting component of the ?-catenin destruction complex, and its stability is regulated by ..
  25. Jho E, Lomvardas S, Costantini F. A GSK3beta phosphorylation site in axin modulates interaction with beta-catenin and Tcf-mediated gene expression. Biochem Biophys Res Commun. 1999;266:28-35 pubmed
    ..b>Axin is a scaffold protein which binds beta-catenin and GSK3beta (as well as several other proteins) and thus promotes ..
  26. Luo W, Zou H, Jin L, Lin S, Li Q, Ye Z, et al. Axin contains three separable domains that confer intramolecular, homodimeric, and heterodimeric interactions involved in distinct functions. J Biol Chem. 2005;280:5054-60 pubmed
    b>Axin is a major scaffold protein, interacting with diverse molecules involved in a number of signaling pathways. Axin can undergo dimer/oligomerization via its DIX domain...
  27. Strovel E, Wu D, Sussman D. Protein phosphatase 2Calpha dephosphorylates axin and activates LEF-1-dependent transcription. J Biol Chem. 2000;275:2399-403 pubmed
    ..PP2C exists in a complex with Dvl, beta-catenin, and Axin, a negative regulator of Wnt signaling...
  28. Satoh S, Daigo Y, Furukawa Y, Kato T, Miwa N, Nishiwaki T, et al. AXIN1 mutations in hepatocellular carcinomas, and growth suppression in cancer cells by virus-mediated transfer of AXIN1. Nat Genet. 2000;24:245-50 pubmed
    ..cancer cells that had accumulated beta-catenin as a consequence of either APC, CTNNB1 or AXIN1 mutation, suggesting that axin may be an effective therapeutic molecule for suppressing growth of hepatocellular and colorectal cancers.
  29. Sakanaka C, Williams L. Functional domains of axin. Importance of the C terminus as an oligomerization domain. J Biol Chem. 1999;274:14090-3 pubmed
    To understand the mechanism of how Axin acts as an inhibitory molecule in the Wnt pathway, we generated a series of mutated forms of Axin...
  30. Rui Y, Xu Z, Xiong B, Cao Y, Lin S, Zhang M, et al. A beta-catenin-independent dorsalization pathway activated by Axin/JNK signaling and antagonized by aida. Dev Cell. 2007;13:268-82 pubmed
    b>Axin is a scaffold protein that controls multiple important pathways, including the canonical Wnt pathway and JNK signaling...
  31. Lu Z, Liu W, Huang H, He Y, Han Y, Rui Y, et al. Protein encoded by the Axin(Fu) allele effectively down-regulates Wnt signaling but exerts a dominant negative effect on c-Jun N-terminal kinase signaling. J Biol Chem. 2008;283:13132-9 pubmed publisher
    b>Axin plays an architectural role in many important signaling pathways that control various aspects of development and tumorigenesis, including the Wnt, transforming growth factor-beta, MAP kinase pathways, as well as p53 activation ..
  32. Li P, Li J, Yin F, Yan J, Feng X, Li Z, et al. [Alterations of Axin protein expression during cardiac remodeling in rats]. Sheng Li Xue Bao. 2003;55:331-5 pubmed
    The purpose of the present study was to observe the expression of Axin protein during cardiac remodeling in rats...
  33. Fiedler M, Mendoza Topaz C, Rutherford T, Mieszczanek J, Bienz M. Dishevelled interacts with the DIX domain polymerization interface of Axin to interfere with its function in down-regulating ?-catenin. Proc Natl Acad Sci U S A. 2011;108:1937-42 pubmed publisher
    ..In the absence of Wnt, ?-catenin is targeted continuously for proteasomal degradation by the Axin destruction complex, whose activity is blocked upon Wnt stimulation by Dishevelled, which recruits Axin to the ..
  34. Zhang L, Ye J, Zhang F, Li F, Li H, Gu Y, et al. Axin induces cell death and reduces cell proliferation in astrocytoma by activating the p53 pathway. Int J Oncol. 2009;35:25-32 pubmed
    Astrocytic tumors are the most common brain tumors with various genetic defects. As a tumor suppressor gene, Axin could control cell death and growth...
  35. Kadoya T, Kishida S, Fukui A, Hinoi T, Michiue T, Asashima M, et al. Inhibition of Wnt signaling pathway by a novel axin-binding protein. J Biol Chem. 2000;275:37030-7 pubmed
    b>Axin forms a complex with adenomatous polyposis coli gene product, glycogen synthase kinase-3beta (GSK-3beta), beta-catenin, Dvl, and protein phosphatase 2A and functions as a scaffold protein in the Wnt signaling pathway...
  36. Liu C, Li Y, Semenov M, Han C, Baeg G, Tan Y, et al. Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism. Cell. 2002;108:837-47 pubmed
    ..which is believed to be performed by glycogen synthase kinase-3 (GSK-3) in complex with tumor suppressor proteins Axin and adnomatous polyposis coli (APC)...
  37. Shibata N, Tomimoto Y, Hanamura T, Yamamoto R, Ueda M, Ueda Y, et al. Crystallization and preliminary X-ray crystallographic studies of the axin DIX domain. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2007;63:529-31 pubmed
    b>Axin is a negative regulator of the canonical Wnt signalling pathway that mediates the phosphorylation of beta-catenin by glycogen synthase kinase 3beta...
  38. Rakyan V, Chong S, Champ M, Cuthbert P, Morgan H, Luu K, et al. Transgenerational inheritance of epigenetic states at the murine Axin(Fu) allele occurs after maternal and paternal transmission. Proc Natl Acad Sci U S A. 2003;100:2538-43 pubmed
    ..The molecular basis of this phenomenon, however, is largely a mystery. Axin-fused (Axin(Fu)), first identified in 1937, is a classic example of a mammalian allele displaying extremely ..
  39. Wang H, Tekpetey F, Kidder G. Identification of WNT/beta-CATENIN signaling pathway components in human cumulus cells. Mol Hum Reprod. 2009;15:11-7 pubmed publisher
    ..We also identified DVL (disheveled), AXIN, GSK-3beta (glycogen synthase kinase-3beta) and beta-CATENIN. beta-CATENIN is concentrated in the plasma membranes...
  40. Luo W, Ng W, Jin L, Ye Z, Han J, Lin S. Axin utilizes distinct regions for competitive MEKK1 and MEKK4 binding and JNK activation. J Biol Chem. 2003;278:37451-8 pubmed
    b>Axin is a multidomain protein that plays a critical role in Wnt signaling, serving as a scaffold for down-regulation of beta-catenin. It also activates the JNK mitogen-activated protein kinase by binding to MEKK1...
  41. Tang Y, Liu Z, Zhao L, Clemens T, Cao X. Smad7 stabilizes beta-catenin binding to E-cadherin complex and promotes cell-cell adhesion. J Biol Chem. 2008;283:23956-63 pubmed publisher
    ..A Smad7-Axin interaction disassociates GSK-3beta and beta-catenin from Axin, as well as inhibits the recruitment of Smurf2, an ..
  42. Anderson C, Neufeld K, White R. Subcellular distribution of Wnt pathway proteins in normal and neoplastic colon. Proc Natl Acad Sci U S A. 2002;99:8683-8 pubmed
    ..APC and associated proteins thus form a beta-catenin regulatory complex, with axin playing a key role...
  43. Dunn L, Caspari E. A case of neighboring loci with similar effects. Genetics. 1945;30:543-68 pubmed
  44. Hino S, Kishida S, Michiue T, Fukui A, Sakamoto I, Takada S, et al. Inhibition of the Wnt signaling pathway by Idax, a novel Dvl-binding protein. Mol Cell Biol. 2001;21:330-42 pubmed
    ..we identified a novel protein which binds to the PDZ domain of Dvl and named it Idax (for inhibition of the Dvl and Axin complex). Idax and Axin competed with each other for the binding to Dvl...
  45. Hirabayashi S, Nishimura W, Iida J, Kansaku A, Kishida S, Kikuchi A, et al. Synaptic scaffolding molecule interacts with axin. J Neurochem. 2004;90:332-9 pubmed
    ..It interacts with N-methyl-d-aspartate receptor subunits, neuroligin, and beta-catenin. Here, we identified Axin as a novel binding partner of S-SCAM...
  46. Fagotto F, Jho E, Zeng L, Kurth T, Joos T, Kaufmann C, et al. Domains of axin involved in protein-protein interactions, Wnt pathway inhibition, and intracellular localization. J Cell Biol. 1999;145:741-56 pubmed
    b>Axin was identified as a regulator of embryonic axis induction in vertebrates that inhibits the Wnt signal transduction pathway...
  47. Hart M, de los Santos R, Albert I, Rubinfeld B, Polakis P. Downregulation of beta-catenin by human Axin and its association with the APC tumor suppressor, beta-catenin and GSK3 beta. Curr Biol. 1998;8:573-81 pubmed
    ..In a Xenopus developmental system, Wnt-1 signaling was inhibited by Axin, the product of the murine fused gene...