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Role of APC and Its Binding Partners in Regulating Microtubules in Mitosis

  • Shirin Bahmanyar
  • W. James Nelson
  • Angela I. M. Barth
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 656)

Abstract

Adenomatous polyposis coli (APC) is a multifunctional protein commonly mutated in colon cancer. APC contains binding sites for multiple proteins with diverse roles in signaling and the structural and functional organization of cells. Recent evidence suggests roles for APC and some of its binding partners in regulating microtubules in mitosis. APC localizes to three key locations in mitosis: kinetochores, the cortex and centrosomes. Here, we discuss possible mechanisms for APC function at these sites and suggest new pathways by which APC mutations promote tumorigenesis.

Keywords

Adenomatous Polyposis Coli Mitotic Spindle Adenomatous Polyposis Coli Gene Spindle Pole Body Adenomatous Polyposis Coli Mutation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Kinzler KW, Vogelstein B. Lessons from hereditary colorectal cancer. Cell 1996; 87(2):159–170.CrossRefPubMedGoogle Scholar
  2. 2.
    Polakis P. The adenomatous polyposis coli (APC) tumor suppressor. Biochim Biophys Acta 1997; 1332(3):F127–147.PubMedGoogle Scholar
  3. 3.
    Kishida S, Yamamoto H, Ikeda S et al. Axin, a negative regulator of the wnt signaling pathway, directly interacts with adenomatous polyposis coli and regulates the stabilization of beta-catenin. J Biol Chem 1998; 273(18):10823–10826.CrossRefPubMedGoogle Scholar
  4. 4.
    Rubinfeld B, Tice DA, Polakis P. Axin-dependent phosphorylation of the adenomatous polyposis coli protein mediated by casein kinase lepsilon. J Biol Chem 2001; 276(42):39037–39045.CrossRefPubMedGoogle Scholar
  5. 5.
    Sakanaka C, Weiss JB, Williams LT. Bridging of beta-catenin and glycogen synthase kinase-3beta by axin and inhibition of beta-catenin-rnediated transcription. Proc Natl Acad Sci USA 1998; 95(6):3020–3023.CrossRefPubMedGoogle Scholar
  6. 6.
    Ikeda S, Kishida M, Matsuura Y et al. GSK-3beta-dependent phosphorylation of adenomatous polyposis coli gene product can be modulated by beta-catenin and protein phosphatase 2A complexed with Axin. Oncogene 2000; 19(4):537–545.CrossRefPubMedGoogle Scholar
  7. 7.
    Polakis P. The oncogenic activation of beta-catenin. Curr Opin Genet Dev 1999; 9(1):15–21.CrossRefPubMedGoogle Scholar
  8. 8.
    Munemitsu S, Souza B, Muller O et al. The APC gene product associates with microtubules in vivo and promotes their assembly in vitro. Cancer Res 1994; 54(14):3676–3681.PubMedGoogle Scholar
  9. 9.
    Su LK, Burrell M, Hill DE et al. APC binds to the novel protein EB1. Cancer Res 1995; 55(14):2972–2977.PubMedGoogle Scholar
  10. 10.
    Banks JD, Heald R. Adenomatous polyposis coli associates with the microtubule-destabilizing protein XMCAK. Curr Biol 2004; 14(22):2033–2038.CrossRefPubMedGoogle Scholar
  11. 11.
    Jimbo T, Kawasaki Y, Koyama R et al. Identification of a link between the tumour suppressor APC and the kinesin superfamily. Nat Cell Biol 2002; 4(4):323–327.CrossRefPubMedGoogle Scholar
  12. 12.
    Wen Y, Eng CH, Schmoranzer J et al. EB1 and APC bind to mDia to stabilize microtubules downstream of Rho and promote cell migration. Nat Cell Biol 2004; 6(9):820–830.CrossRefPubMedGoogle Scholar
  13. 13.
    Nathke IS, Adams CL, Polakis P et al. The adenomatous polyposis coli tumor suppressor protein localizes to plasma membrane sites involved in active cell migration. J Cell Biol 1996; 134(1):165–179.CrossRefPubMedGoogle Scholar
  14. 14.
    Zhou FQ, Zhou J, Dedhar S et al. NGF-induced axon growth is mediated by localized inactivation of GSK-3beta and functions of the microtubule plus end binding protein APC. Neuron 2004; 42(6):897–912.CrossRefPubMedGoogle Scholar
  15. 15.
    Fodde R, Kuipers J, Rosenberg C et al. Mutations in the APC tumour suppressor gene cause chromosomal instability. Nat Cell Biol 2001; 3(4):433–438.CrossRefPubMedGoogle Scholar
  16. 16.
    Kaplan KB, Burds AA, Swedlow JR et al. A role for the adenomatous polyposis coli protein in chromosome segregation. Nat Cell Biol 2001; 3(4):429–432.CrossRefPubMedGoogle Scholar
  17. 17.
    McCartney BM, Dierick HA, Kirkpatrick C et al. Drosophila APC2 is a cytoskeletally-associated protein that regulates wingless signaling in the embryonic epidermis. J Cell Biol 1999; 146(6):1303–1318.CrossRefPubMedGoogle Scholar
  18. 18.
    McCartney BM, McEwen DG, Grevengoed E et al. Drosophila APC2 and armadillo participate in tethering mitotic spindles to cortical actin. Nat Cell Biol 2001; 3(10):933–938.CrossRefPubMedGoogle Scholar
  19. 19.
    Louie RK, Bahmanyar S, Siemers KA et al. Adenomatous polyposis coli and EB1 localize in close proximity of the mother centriole and EB1 is a functional component of centrosomes. J Cell Sci 2004; 117(Pt 7):1117–1128.CrossRefPubMedGoogle Scholar
  20. 20.
    Biggins S, Walczak CE. Captivating capture: how microtubules attach to kinetochores. Curr Biol 2003; 13(11):R449–460.CrossRefPubMedGoogle Scholar
  21. 21.
    Rieder CL, Salmon ED. The vertebrate cell kinetochore and its roles during mitosis. Trends Cell Biol 1998; 8(8):310–318.CrossRefPubMedGoogle Scholar
  22. 22.
    Green RA, Kaplan KB. Chromosome instability in colorectal tumor cells is associated with defects in microtubule plus-end attachments caused by a dominant mutation in APC. J Cell Biol 2003; 163(5):949–961.CrossRefPubMedGoogle Scholar
  23. 23.
    Draviam VM, Shapiro I, Aldridge B et al. Misorientation and reduced stretching of aligned sister kinetochores promote chromosome missegregation in EB1-or APC-depleted cells. EMBO J 2006; 25(12):2814–2827.CrossRefPubMedGoogle Scholar
  24. 24.
    Dikovskaya D, Schiffmann D, Newton IP et al. Loss of APC induces polyploidy due to a combination of defects in mitosis and apoptosis. J Cell Biol, in press 2006.Google Scholar
  25. 25.
    Kita K, Wittmann T, Nathke IS et al. Adenomatous polyposis coli on microtubule plus ends in cell extensions can promote microtubule net growth with or without EB1. Mol Biol Cell 2006; 17(5):2331–2345.CrossRefPubMedGoogle Scholar
  26. 26.
    Dikovskaya D, Newton IP, Nathke IS. The adenomatous polyposis coli protein is required for the formation of robust spindles formed in CSF Xenopus extracts. Mol Biol Cell 2004; 15(6):2978–2991.CrossRefPubMedGoogle Scholar
  27. 27.
    Kroboth K, Newton IP, Kita K et al. Lack of adenomatous polyposiscoli protein correlates with a decrease in cell migration and overall changes in microtubule stability. Mol Biol Cell 2007; 18(3):910–918.CrossRefPubMedGoogle Scholar
  28. 28.
    Pinsky BA, Biggins S. The spindle checkpoint: tension versus attachment. Trends Cell Biol 2005; 15(9):486–493.CrossRefPubMedGoogle Scholar
  29. 29.
    Dikovskaya D, Zumbrunn J, Penman GA et al. The adenomatous polyposis coli protein: in the limelight out at the edge. Trends Cell Biol 2001; 11(9):378–384.CrossRefPubMedGoogle Scholar
  30. 30.
    Kinoshita K, Noetzel TL, Arnal I et al. Global and local control of microtubule destabilization promoted by a catastrophe kinesin MCAK/XKCM1. J Muscle Res Cell Motil 2006; 27(2):107–114.CrossRefPubMedGoogle Scholar
  31. 31.
    Ahringer J. Control of cell polarity and mitotic spindle positioning in animal cells. Curr Opin Cell Biol 2003; 15(1):73–81.CrossRefPubMedGoogle Scholar
  32. 32.
    Manneville JB, Etienne-Manneville S. Positioning centrosomes and spindle poles: looking at the periphery to find the centre. Biol Cell 2006; 98(9):557–565.CrossRefPubMedGoogle Scholar
  33. 33.
    Beach DL, Thibodeaux J, Maddox P et al. The role of the proteins Kar9 and Myo2 in orienting the mitotic spindle of budding yeast. Curr Biol 2000; 10(23):1497–1506.CrossRefPubMedGoogle Scholar
  34. 34.
    Bloom K. It’s a kar9ochore to capture microtubules. Nat Cell Biol 2000; 2(6):E96–98.CrossRefPubMedGoogle Scholar
  35. 35.
    Lee L, Tirnauer JS, Li J et al. Positioning of the mitotic spindle by a cortical-microtubule capture mechanism. Science 2000; 287(5461):2260–2262.CrossRefPubMedGoogle Scholar
  36. 36.
    Korinek WS, Copeland MJ, Chaudhuri A et al. Molecular linkage underlying microtubule orientation toward cortical sites in yeast. Science. Mar 24 2000; 287(5461):2257–2259.Google Scholar
  37. 37.
    Lu B, Roegiers F, Jan LY et al. Adherens junctions inhibit asymmetric division in the drosophila epithelium. Nature 2001; 409(6819):522–525.CrossRefPubMedGoogle Scholar
  38. 38.
    Yamashita YM, Jones DL, Fuller MT. Orientation of asymmetric stem cell division by the APC tumor suppressor and centrosome. Science 2003; 301(5639):1547–1550.CrossRefPubMedGoogle Scholar
  39. 39.
    Green RA, Wollman R, Kaplan KB. APC and EB1 function together in mitosis to regulate spindle dynamics and chromosome alignment. Mol Biol Cell 2005; 16(10):4609–4622.CrossRefPubMedGoogle Scholar
  40. 40.
    Paoletti A, Bornens M. Kar9 asymmetrical loading on spindle poles mediates proper spindle alignment in budding yeast. Dev Cell 2003; 4(3):289–290.CrossRefPubMedGoogle Scholar
  41. 41.
    Liakopoulos D, Kusch J, Grava S et al. Asymmetric loading of Kar9 onto spindle poles and microtubules ensures proper spindle alignment. Cell 2003; 112(4):561–574.CrossRefPubMedGoogle Scholar
  42. 42.
    Theesfeld CL, Irazoqui JE, Bloom K et al. The role of actin in spindle orientation changes during the Saccharomyces cerevisiae cell cycle. J Cell Biol 1999; 146(5):1019–1032.CrossRefPubMedGoogle Scholar
  43. 43.
    Hwang E, Kusch J, Barral Y et al. Spindle orientation in saccharomyces cerevisiae depends on the transport of microtubule ends along polarized actin cables. J Cell Biol 2003; 161(3):483–488.CrossRefPubMedGoogle Scholar
  44. 44.
    Pearson CG, Bloom K. Dynamic microtubules lead the way for spindle positioning. Nat Rev Mol Cell Biol 2004; 5(6):481–492.CrossRefPubMedGoogle Scholar
  45. 45.
    Yu X, Waltzer L, Bienz M. A new drosophila APC homologue associated with adhesive zones of epithelial cells. Nat Cell Biol 1999; 1(3):144–151.CrossRefPubMedGoogle Scholar
  46. 46.
    Nakagawa H, Murata Y, Koyama K et al. Identification of a brain-specific APC homologue, APCL and its interaction with beta-catenin. Cancer Res 1998; 58(22):5176–5181.PubMedGoogle Scholar
  47. 47.
    McCartney BM, Price MH, Webb RL et al. Testing hypotheses for the functions of APC family proteins using null and truncation alleles in drosophila. Development 2006; 133(12):2407–2418.CrossRefPubMedGoogle Scholar
  48. 48.
    van Es JH, Kirkpatrick C, van de Wetering M et al. Identification of APC2, a homologue of the adenomatous polyposis coli tumour suppressor. Curr Biol 1999; 9(2):105–108.Google Scholar
  49. 49.
    Mimori-Kiyosue Y, Tsukita S. Where is APC going? J Cell Biol 2001; 154(6):1105–1109.CrossRefPubMedGoogle Scholar
  50. 50.
    Barth AI, Nathke IS, Nelson WJ. Cadherins, catenins and APC protein: Interplay between cytoskeletal complexes and signaling pathways. Curr Opin Cell Biol 1997; 9(5):683–690.CrossRefPubMedGoogle Scholar
  51. 51.
    Bienz M, Hamada F. Adenomatous polyposis coli proteins and cell adhesion. Curr Opin Cell Biol 2004; 16(5):528–535.CrossRefPubMedGoogle Scholar
  52. 52.
    Barth AI, Nelson WJ. What can humans learn from flies about adenomatous polyposis coli? Bioessays 2002; 24(9):771–774.CrossRefPubMedGoogle Scholar
  53. 53.
    Mimori-Kiyosue Y, Shiina N, Tsukita S. Adenomatous polyposis coli (APC) protein moves along microtubules and concentrates at their growing ends in epithelial cells. J Cell Biol 2000; 148(3):505–518.CrossRefPubMedGoogle Scholar
  54. 54.
    Rogers SL, Rogers GC, Sharp DJ et al. Drosophila EB1 is important for proper assembly, dynamics and positioning of the mitotic spindle. J Cell Biol 2002; 158(5):873–884.CrossRefPubMedGoogle Scholar
  55. 55.
    Mimori-Kiyosue Y, Shiina N, Tsukita S. The dynamic behavior of the APC-binding protein EB1 on the distal ends of microtubules. Curr Biol 2000; 10(14):865–868.CrossRefPubMedGoogle Scholar
  56. 56.
    Reilein A, Nelson WJ. APC is a component of an organizing template for cortical microtubule networks. Nat Cell Biol 2005; 7(5):463–473.CrossRefPubMedGoogle Scholar
  57. 57.
    Reilein A, Yamada S, Nelson WJ. Self-organization of an acentrosomal microtubule network at the basal cortex of polarized epithelial cells. J Cell Biol 2005; 171(5):845–855.CrossRefPubMedGoogle Scholar
  58. 58.
    Miller RK, Rose MD. Kar9p is a novel cortical protein required for cytoplasmic microtubule orientation in yeast. J Cell Biol 1998; 140(2):377–390.CrossRefPubMedGoogle Scholar
  59. 59.
    Murphy SM, Stearns T. Cytoskeleton: Microtubule nucleation takes shape. Curr Biol 1996; 6(6):642–644.CrossRefPubMedGoogle Scholar
  60. 60.
    Bornens M. Centrosome composition and microtubule anchoring mechanisms. Curr Opin Cell Biol 2002; 14(1):25–34.CrossRefPubMedGoogle Scholar
  61. 61.
    Peifer M, Polakis P. Wnt signaling in oncogenesis and embryogenesis-A look outside the nucleus. Science 2000; 287(5458):1606–1609.CrossRefPubMedGoogle Scholar
  62. 62.
    Kaplan DD, Meigs TE, Kelly P et al. Identification of a role for beta-catenin in the establishment of a bipolar mitotic spindle. J Biol Chem 2004; 279(12):10829–10832.CrossRefPubMedGoogle Scholar
  63. 63.
    Bahmanyar S, Kaplan DD, DeLuca JG et al. β-catenin is a Nek2 substrate involved in centrosome separation. Genes Dev 2006; 22(1):91–105.CrossRefGoogle Scholar
  64. 64.
    Huang P, Senga T, Hamaguchi M. A novel role of phospho-beta-carenin in microtubule regrowth at centrosome. Oncogene 2007; 26(30):4357–4371.CrossRefPubMedGoogle Scholar
  65. 65.
    Ligon LA, Karki S, Tokiro M et al. Dynein binds to beta-catenin and may tether microtubules at adherens junctions. Nat Cell Biol 2001; 3(10):913–917.CrossRefPubMedGoogle Scholar
  66. 66.
    Wakefield JG, Stephens DJ, Tavare JM. A role for glycogen synthase kinase-3 in mitotic spindle dynamics and chromosome alignment. J Cell Sci 2003; 116(Pt 4):637–646.CrossRefPubMedGoogle Scholar
  67. 67.
    Freed E, Lacey KR, Huie P et al. Components of an SCF ubiquitin ligase localize to the centrosome and regulate the centrosome duplication cycle. Genes Dev 1999; 13(17):2242–2257.CrossRefPubMedGoogle Scholar
  68. 68.
    Wojcik EJ, Glover DM, Hays TS. The SCF ubiquitin ligase protein slimb regulates centrosome duplication in Drosophila. Curr Biol 2000; 10(18):1131–1134.CrossRefPubMedGoogle Scholar
  69. 69.
    Fabunmi RP, Wigley WC, Thomas PJ et al. Activity and regulation of the centrosome-associated proteasome. J Biol Chem 2000; 275(1):409–413.CrossRefPubMedGoogle Scholar
  70. 70.
    McDonald HB, Byers B. A proteasome cap subunit required for spindle pole body duplication in yeast. J Cell Biol 1997; 137(3):539–553.CrossRefPubMedGoogle Scholar
  71. 71.
    Winey M, Baum P, Goetsch L et al. Genetic determinants of spindle pole body duplication in budding yeast. Cold Spring Harb Symp Quant Biol 1991; 56:705–708.PubMedGoogle Scholar
  72. 72.
    Schlessinger K ME, Hall A. Cdc42 and noncanonical Wnt signal transduction pathways cooperate to promote cell polarity. J Cell Biol 2007; 178(3):355–361.CrossRefPubMedGoogle Scholar
  73. 73.
    Penman GA, Leung L, Nathke IS. The adenomatous polyposis coli protein (APC) exists in two distinct soluble complexes with different functions. J Cell Sci 2005; 118(Pt 20):4741–4750.CrossRefPubMedGoogle Scholar
  74. 74.
    Zumbrunn J, Kinoshita K, Hyman AA et al. Binding of the adenomatous polyposis coli protein to microtubules increases microtubule stability and is regulated by GSK3 beta phosphorylation. Curr Biol 2001; 11(1):44–49.CrossRefPubMedGoogle Scholar
  75. 75.
    Bienz M, Clevers H. Linking colorectal cancer to Wnt signaling. Cell 2000; 103(2):311–320.CrossRefPubMedGoogle Scholar
  76. 76.
    Michor F, Iwasa Y, Lengauer C et al. Dynamics of colorectal cancer. Semin Cancer Biol 2005; 15(6):484–493.CrossRefPubMedGoogle Scholar
  77. 77.
    Lengauer C, Kinzler KW, Vogelstein B. Genetic instability in colorectal cancers. Nature 1997; 386(6625):623–627.CrossRefPubMedGoogle Scholar
  78. 78.
    Lengauer C, Kinzler KW, Vogelstein B. Genetic instabilities in human cancers. Nature 1998; 396(6712):643–649.CrossRefPubMedGoogle Scholar
  79. 79.
    Nowak MA, Komarova NL, Sengupta A et al. The role of chromosomal instability in tumor initiation. Proc Natl Acad Sci USA 2002; 99(25):16226–16231.CrossRefPubMedGoogle Scholar
  80. 80.
    Rajagopalan H, Nowak MA, Vogelstein B et al. The significance of unstable chromosomes in colorectal cancer. Nat Rev Cancer 2003; 3(9):695–701.CrossRefPubMedGoogle Scholar
  81. 81.
    Giaretti W, Venesio T, Prevosto C et al. Chromosomal instability and APC gene mutations in human sporadic colorectal adenomas. J Pathol 2004; 204(2):193–199.CrossRefPubMedGoogle Scholar
  82. 82.
    Draviam VM, Xie S, Sorger PK. Chromosome segregation and genomic stability. Curr Opin Genet Dev 2004; 14(2):120–125.CrossRefPubMedGoogle Scholar
  83. 83.
    Michor F, Iwasa Y, Vogelstein B et al. Can chromosomal instability initiate tumorigenesis? Semin Cancer Biol 2005; 15(1):43–49.CrossRefPubMedGoogle Scholar
  84. 84.
    Brinkley BR, Goepfert TM. Supernumerary centrosomes and cancer: Boveri’s hypothesis resurrected. Cell Motil Cytoskeleton 1998; 41(4):281–288.CrossRefPubMedGoogle Scholar
  85. 85.
    Nigg EA. Centrosome aberrations: Cause or consequence of cancer progression? Nat Rev Cancer 2002; 2(11):815–825.CrossRefPubMedGoogle Scholar
  86. 86.
    Tighe A, Johnson VL, Albertella M et al. Aneuploid colon cancer cells have a robust spindle checkpoint. EMBO Rep 2001; 2(7):609–614.CrossRefPubMedGoogle Scholar
  87. 87.
    Akong, K, Grevengoed EE, Price MH et al. Drosophila APC2 and APC1 play overlapping roles in wingless signaling in the embryo and imaginal discs. Development 2002; 250:91–100.Google Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2009

Authors and Affiliations

  • Shirin Bahmanyar
    • 1
    • 2
  • W. James Nelson
    • 1
    • 2
  • Angela I. M. Barth
    • 1
  1. 1.Department of Biological Sciences, Bio-X Program, The James H. Clark CenterStanford UniversityStanfordUSAUSA
  2. 2.Department of Biological Sciences and Molecular Cellular PhysiologyStanford UniversityStanfordUSA

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