Cell cycle progression by the repression of primary cilia formation in proliferating cells

Polo SE, Jackson SP (2011) Dynamics of DNA damage response proteins at DNA breaks: a focus on protein modifications. Genes Dev 25(5):409–433. doi:10.1101/gad.2021311 Langerak P, Russell P (2011) Regulatory networks integrating cell cycle control with DNA damage checkpoints and double-strand break repair. Philos Trans R Soc Lond B Biol Sci 366(1584):3562–3571. doi:10.1098/rstb.2011.0070 Medema RH, Macurek L (2012) Checkpoint control and cancer. Oncogene 31(21):2601–2613. doi:10.1038/onc.2011.451 Ciccia A, Elledge SJ (2010) The DNA damage response: making it safe to play with knives. Mol Cell 40(2):179–204. doi:10.1016/j.molcel.2010.09.019 Jackson SP, Bartek J (2009) The DNA-damage response in human biology and disease. Nature 461(7267):1071–1078. doi:10.1038/nature08467 Bartek J, Lukas J (2007) DNA damage checkpoints: from initiation to recovery or adaptation. Curr Opin Cell Biol 19(2):238–245. doi:10.1016/j.ceb.2007.02.009 McGowan CH, Russell P (2004) The DNA damage response: sensing and signaling. Curr Opin Cell Biol 16(6):629–633. doi:10.1016/j.ceb.2004.09.005 Niida H, Nakanishi M (2006) DNA damage checkpoints in mammals. Mutagenesis 21(1):3–9. doi:10.1093/mutage/gei063 McGowan CH (2002) Checking in on Cds1 (Chk2): a checkpoint kinase and tumor suppressor. BioEssays 24(6):502–511. doi:10.1002/bies.10101 Appella E, Anderson CW (2001) Post-translational modifications and activation of p53 by genotoxic stresses. Eur J Biochem/FEBS 268(10):2764–2772. doi:10.1046/j.1432-1327.2001.02225.x Riley T, Sontag E, Chen P, Levine A (2008) Transcriptional control of human p53-regulated genes. Nat Rev Mol Cell Biol 9(5):402–412. doi:10.1038/nrm2395 Goto H, Izawa I, Li P, Inagaki M (2012) Novel regulation of checkpoint kinase 1: is checkpoint kinase 1 a good candidate for anti-cancer therapy? Cancer Sci 103(7):1195–1200. doi:10.1111/j.1349-7006.2012.02280.x Kops GJ, Shah JV (2012) Connecting up and clearing out: how kinetochore attachment silences the spindle assembly checkpoint. Chromosoma. doi:10.1007/s00412-012-0378-5 Musacchio A, Salmon ED (2007) The spindle-assembly checkpoint in space and time. Nat Rev Mol Cell Biol 8(5):379–393. doi:10.1038/nrm2163 Carmena M (2012) Abscission checkpoint control: stuck in the middle with Aurora B. Open Biol 2(7):120095. doi:10.1098/rsob.120095 Bartek J, Bartkova J, Lukas J (1996) The retinoblastoma protein pathway and the restriction point. Curr Opin Cell Biol 8(6):805–814. doi:10.1016/S0955-0674(96)80081-0 Morgan DO (1997) Cyclin-dependent kinases: engines, clocks, and microprocessors. Annu Rev Cell Dev Biol 13:261–291. doi:10.1146/annurev.cellbio.13.1.261 Mittnacht S (1998) Control of pRB phosphorylation. Curr Opin Genet Dev 8(1):21–27. doi:10.1016/S0959-437X(98)80057-9 Sage J (2004) Cyclin C makes an entry into the cell cycle. Dev Cell 6(5):607–608. doi:10.1016/S1534-5807(04)00137-6 Sun A, Bagella L, Tutton S, Romano G, Giordano A (2007) From G0 to S phase: a view of the roles played by the retinoblastoma (Rb) family members in the Rb-E2F pathway. J Cell Biochem 102(6):1400–1404. doi:10.1002/jcb.21609 Ren S, Rollins BJ (2004) Cyclin C/cdk3 promotes Rb-dependent G0 exit. Cell 117(2):239–251. doi:10.1016/S0092-8674(04)00300-9 Deshpande A, Sicinski P, Hinds PW (2005) Cyclins and cdks in development and cancer: a perspective. Oncogene 24(17):2909–2915. doi:10.1038/sj.onc.1208618 Tucker RW, Pardee AB, Fujiwara K (1979) Centriole ciliation is related to quiescence and DNA synthesis in 3T3 cells. Cell 17(3):527–535. doi:10.1016/0092-8674(79)90261-7 Singla V, Reiter JF (2006) The primary cilium as the cell’s antenna: signaling at a sensory organelle. Science 313(5787):629–633. doi:10.1126/science.1124534 Anderson CT, Castillo AB, Brugmann SA, Helms JA, Jacobs CR, Stearns T (2008) Primary cilia: cellular sensors for the skeleton. Anat Rec (Hoboken) 291(9):1074–1078. doi:10.1002/ar.20754 Nigg EA, Raff JW (2009) Centrioles, centrosomes, and cilia in health and disease. Cell 139(4):663–678. doi:10.1016/j.cell.2009.10.036 Gerdes JM, Davis EE, Katsanis N (2009) The vertebrate primary cilium in development, homeostasis, and disease. Cell 137(1):32–45. doi:10.1016/j.cell.2009.03.023 Ishikawa H, Marshall WF (2011) Ciliogenesis: building the cell’s antenna. Nat Rev Mol Cell Biol 12(4):222–234. doi:10.1038/nrm3085 Goetz SC, Anderson KV (2010) The primary cilium: a signalling centre during vertebrate development. Nat Rev Genet 11(5):331–344. doi:10.1038/nrg2774 Seeley ES, Nachury MV (2010) The perennial organelle: assembly and disassembly of the primary cilium. J Cell Sci 123(Pt 4):511–518. doi:10.1242/jcs.061093 Quarmby LM, Parker JD (2005) Cilia and the cell cycle? J Cell Biol 169(5):707–710. doi:10.1083/jcb.200503053 Kobayashi T, Dynlacht BD (2011) Regulating the transition from centriole to basal body. J Cell Biol 193(3):435–444. doi:10.1083/jcb.201101005 Pearson CG, Winey M (2009) Basal body assembly in ciliates: the power of numbers. Traffic 10(5):461–471. doi:10.1111/j.1600-0854.2009.00885.x Tucker RW, Scher CD, Stiles CD (1979) Centriole deciliation associated with the early response of 3T3 cells to growth factors but not to SV40. Cell 18(4):1065–1072. doi:10.1016/0092-8674(79)90219-8 Kim S, Tsiokas L (2011) Cilia and cell cycle re-entry: more than a coincidence. Cell Cycle 10(16):2683–2690. doi:10.4161/cc.10.16.17009 Plotnikova OV, Golemis EA, Pugacheva EN (2008) Cell cycle-dependent ciliogenesis and cancer. Cancer Res 68(7):2058–2061. doi:10.1158/0008-5472.CAN-07-5838 Pan J, Seeger-Nukpezah T, Golemis EA (2012) The role of the cilium in normal and abnormal cell cycles: emphasis on renal cystic pathologies. Cell Mol Life Sci. doi:10.1007/s00018-012-1052-z Bloodgood RA (2009) From central to rudimentary to primary: the history of an underappreciated organelle whose time has come. The primary cilium. Methods Cell Biol 94:3–52. doi:10.1016/S0091-679X(08)94001-2 Riparbelli MG, Callaini G, Megraw TL (2012) Assembly and persistence of primary cilia in dividing Drosophila spermatocytes. Dev Cell 23(2):425–432. doi:10.1016/j.devcel.2012.05.024 Nigg EA (2001) Mitotic kinases as regulators of cell division and its checkpoints. Nat Rev Mol Cell Biol 2(1):21–32. doi:10.1038/35048096 Marumoto T, Zhang D, Saya H (2005) Aurora-A—a guardian of poles. Nat Rev Cancer 5(1):42–50. doi:10.1038/nrc1526 Carmena M, Ruchaud S, Earnshaw WC (2009) Making the Auroras glow: regulation of Aurora A and B kinase function by interacting proteins. Curr Opin Cell Biol 21(6):796–805. doi:10.1016/j.ceb.2009.09.008 Lens SM, Voest EE, Medema RH (2010) Shared and separate functions of polo-like kinases and aurora kinases in cancer. Nat Rev Cancer 10(12):825–841. doi:10.1038/nrc2964 Pugacheva EN, Jablonski SA, Hartman TR, Henske EP, Golemis EA (2007) HEF1-dependent Aurora A activation induces disassembly of the primary cilium. Cell 129(7):1351–1363. doi:10.1016/j.cell.2007.04.035 Kinzel D, Boldt K, Davis EE, Burtscher I, Trumbach D, Diplas B, Attie-Bitach T, Wurst W, Katsanis N, Ueffing M, Lickert H (2010) Pitchfork regulates primary cilia disassembly and left–right asymmetry. Dev Cell 19(1):66–77. doi:10.1016/j.devcel.2010.06.005 Plotnikova OV, Nikonova AS, Loskutov YV, Kozyulina PY, Pugacheva EN, Golemis EA (2012) Calmodulin activation of Aurora-A kinase (AURKA) is required during ciliary disassembly and in mitosis. Mol Biol Cell 23(14):2658–2670. doi:10.1091/mbc.E11-12-1056 Inoko A, Matsuyama M, Goto H, Ohmuro-Matsuyama Y, Hayashi Y, Enomoto M, Ibi M, Urano T, Yonemura S, Kiyono T, Izawa I, Inagaki M (2012) Trichoplein and Aurora A block aberrant primary cilia assembly in proliferating cells. J Cell Biol 197(3):391–405. doi:10.1083/jcb.201106101 Kim S, Zaghloul NA, Bubenshchikova E, Oh EC, Rankin S, Katsanis N, Obara T, Tsiokas L (2011) Nde1-mediated inhibition of ciliogenesis affects cell cycle re-entry. Nat Cell Biol 13(4):351–360. doi:10.1038/ncb2183 Li A, Saito M, Chuang JZ, Tseng YY, Dedesma C, Tomizawa K, Kaitsuka T, Sung CH (2011) Ciliary transition zone activation of phosphorylated Tctex-1 controls ciliary resorption, S-phase entry and fate of neural progenitors. Nat Cell Biol 13(4):402–411. doi:10.1038/ncb2218 Glover DM, Leibowitz MH, McLean DA, Parry H (1995) Mutations in aurora prevent centrosome separation leading to the formation of monopolar spindles. Cell 81(1):95–105. doi:0092-8674(95)90374-7 Pan J, Wang Q, Snell WJ (2004) An aurora kinase is essential for flagellar disassembly in Chlamydomonas. Dev Cell 6(3):445–451. doi:S1534580704000644 Pugacheva EN, Golemis EA (2005) The focal adhesion scaffolding protein HEF1 regulates activation of the Aurora-A and Nek2 kinases at the centrosome. Nat Cell Biol 7(10):937–946. doi:10.1038/ncb1309 Seo S, Asai T, Saito T, Suzuki T, Morishita Y, Nakamoto T, Ichikawa M, Yamamoto G, Kawazu M, Yamagata T, Sakai R, Mitani K, Ogawa S, Kurokawa M, Chiba S, Hirai H (2005) Crk-associated substrate lymphocyte type is required for lymphocyte trafficking and marginal zone B cell maintenance. J Immunol 175(6):3492–3501 Nishizawa M, Izawa I, Inoko A, Hayashi Y, Nagata K, Yokoyama T, Usukura J, Inagaki M (2005) Identification of trichoplein, a novel keratin filament-binding protein. J Cell Sci 118(Pt 5):1081–1090. doi:10.1242/jcs.01667 Ibi M, Zou P, Inoko A, Shiromizu T, Matsuyama M, Hayashi Y, Enomoto M, Mori D, Hirotsune S, Kiyono T, Tsukita S, Goto H, Inagaki M (2011) Trichoplein controls microtubule anchoring at the centrosome by binding to Odf2 and ninein. J Cell Sci 124(Pt 6):857–864. doi:10.1242/jcs.075705 Pitaval A, Tseng Q, Bornens M, Thery M (2010) Cell shape and contractility regulate ciliogenesis in cell cycle-arrested cells. J Cell Biol 191(2):303–312. doi:10.1083/jcb.201004003 Bouton AH, Riggins RB, Bruce-Staskal PJ (2001) Functions of the adapter protein Cas: signal convergence and the determination of cellular responses. Oncogene 20(44):6448–6458. doi:10.1038/sj.onc.1204785 O’Neill GM, Fashena SJ, Golemis EA (2000) Integrin signalling: a new Cas(t) of characters enters the stage. Trends Cell Biol 10(3):111–119. doi:10.1016/S0962-8924(99)01714-6 Plotnikova OV, Pugacheva EN, Golemis EA (2011) Aurora A kinase activity influences calcium signaling in kidney cells. J Cell Biol 193(6):1021–1032. doi:10.1083/jcb.201012061 Hanaoka K, Qian F, Boletta A, Bhunia AK, Piontek K, Tsiokas L, Sukhatme VP, Guggino WB, Germino GG (2000) Co-assembly of polycystin-1 and -2 produces unique cation-permeable currents. Nature 408(6815):990–994. doi:10.1038/35050128 Koulen P, Cai Y, Geng L, Maeda Y, Nishimura S, Witzgall R, Ehrlich BE, Somlo S (2002) Polycystin-2 is an intracellular calcium release channel. Nat Cell Biol 4(3):191–197. doi:10.1038/ncb754 Delmas P (2004) Polycystins: from mechanosensation to gene regulation. Cell 118(2):145–148. doi:10.1016/j.cell.2004.07.007 Delmas P, Padilla F, Osorio N, Coste B, Raoux M, Crest M (2004) Polycystins, calcium signaling, and human diseases. Biochem Biophys Res Commun 322(4):1374–1383. doi:10.1016/j.bbrc.2004.08.044 Gallagher AR, Germino GG, Somlo S (2010) Molecular advances in autosomal dominant polycystic kidney disease. Adv Chronic Kidney Dis 17(2):118–130. doi:10.1053/j.ackd.2010.01.002 Praetorius HA, Spring KR (2001) Bending the MDCK cell primary cilium increases intracellular calcium. J Membr Biol 184(1):71–79. doi:10.1007/s00232-001-0075-4 Akella JS, Wloga D, Kim J, Starostina NG, Lyons-Abbott S, Morrissette NS, Dougan ST, Kipreos ET, Gaertig J (2010) MEC-17 is an alpha-tubulin acetyltransferase. Nature 467(7312):218–222. doi:10.1038/nature09324 Shida T, Cueva JG, Xu Z, Goodman MB, Nachury MV (2010) The major alpha-tubulin K40 acetyltransferase alphaTAT1 promotes rapid ciliogenesis and efficient mechanosensation. Proc Natl Acad Sci USA 107(50):21517–21522. doi:10.1073/pnas.1013728107 Janke C, Bulinski JC (2011) Post-translational regulation of the microtubule cytoskeleton: mechanisms and functions. Nat Rev Mol Cell Biol 12(12):773–786. doi:10.1038/nrm3227 Gaertig J, Cruz MA, Bowen J, Gu L, Pennock DG, Gorovsky MA (1995) Acetylation of lysine 40 in alpha-tubulin is not essential in Tetrahymena thermophila. J Cell Biol 129(5):1301–1310. doi:10.1083/jcb.129.5.1301 Kozminski KG, Diener DR, Rosenbaum JL (1993) High level expression of nonacetylatable alpha-tubulin in Chlamydomonas reinhardtii. Cell Motil Cytoskeleton 25(2):158–170. doi:10.1002/cm.970250205 Zhang Y, Kwon S, Yamaguchi T, Cubizolles F, Rousseaux S, Kneissel M, Cao C, Li N, Cheng HL, Chua K, Lombard D, Mizeracki A, Matthias G, Alt FW, Khochbin S, Matthias P (2008) Mice lacking histone deacetylase 6 have hyperacetylated tubulin but are viable and develop normally. Mol Cell Biol 28(5):1688–1701. doi:10.1128/MCB.01154-06 Cueva JG, Hsin J, Huang KC, Goodman MB (2012) Posttranslational acetylation of alpha-tubulin constrains protofilament number in native microtubules. Curr Biol 22(12):1066–1074. doi:10.1016/j.cub.2012.05.012 Topalidou I, Keller C, Kalebic N, Nguyen KC, Somhegyi H, Politi KA, Heppenstall P, Hall DH, Chalfie M (2012) Genetically separable functions of the MEC-17 tubulin acetyltransferase affect microtubule organization. Curr Biol 22(12):1057–1065. doi:10.1016/j.cub.2012.03.066 Jackson PK (2011) Do cilia put brakes on the cell cycle? Nat Cell Biol 13(4):340–342. doi:10.1038/ncb0411-340 Efimov VP, Morris NR (2000) The LIS1-related NUDF protein of Aspergillus nidulans interacts with the coiled-coil domain of the NUDE/RO11 protein. J Cell Biol 150(3):681–688. doi:10.1083/jcb.150.3.681 King SM, Dillman JF 3rd, Benashski SE, Lye RJ, Patel-King RS, Pfister KK (1996) The mouse t-complex-encoded protein Tctex-1 is a light chain of brain cytoplasmic dynein. J Biol Chem 271(50):32281–32287. doi:10.1074/jbc.271.50.32281 Pfister KK, Fisher EM, Gibbons IR, Hays TS, Holzbaur EL, McIntosh JR, Porter ME, Schroer TA, Vaughan KT, Witman GB, King SM, Vallee RB (2005) Cytoplasmic dynein nomenclature. J Cell Biol 171(3):411–413. doi:10.1083/jcb.200508078 Malone AM, Anderson CT, Tummala P, Kwon RY, Johnston TR, Stearns T, Jacobs CR (2007) Primary cilia mediate mechanosensing in bone cells by a calcium-independent mechanism. Proc Natl Acad Sci USA 104(33):13325–13330. doi:10.1073/pnas.0700636104 Robert A, Margall-Ducos G, Guidotti JE, Bregerie O, Celati C, Brechot C, Desdouets C (2007) The intraflagellar transport component IFT88/polaris is a centrosomal protein regulating G1–S transition in non-ciliated cells. J Cell Sci 120(Pt 4):628–637. doi:10.1242/jcs.03366 Delaval B, Bright A, Lawson ND, Doxsey S (2011) The cilia protein IFT88 is required for spindle orientation in mitosis. Nat Cell Biol 13(4):461–468. doi:10.1038/ncb2202 Follit JA, Tuft RA, Fogarty KE, Pazour GJ (2006) The intraflagellar transport protein IFT20 is associated with the Golgi complex and is required for cilia assembly. Mol Biol Cell 17(9):3781–3792. doi:10.1091/mbc.E06-02-0133 Ren XD, Kiosses WB, Schwartz MA (1999) Regulation of the small GTP-binding protein Rho by cell adhesion and the cytoskeleton. EMBO J 18(3):578–585. doi:10.1093/emboj/18.3.578 Mikule K, Delaval B, Kaldis P, Jurcyzk A, Hergert P, Doxsey S (2007) Loss of centrosome integrity induces p38–p53–p21-dependent G1–S arrest. Nat Cell Biol 9(2):160–170. doi:10.1038/ncb1529 Katayama H, Sasai K, Kawai H, Yuan ZM, Bondaruk J, Suzuki F, Fujii S, Arlinghaus RB, Czerniak BA, Sen S (2004) Phosphorylation by aurora kinase A induces Mdm2-mediated destabilization and inhibition of p53. Nat Genet 36(1):55–62. doi:10.1038/ng1279 Liu Q, Kaneko S, Yang L, Feldman RI, Nicosia SV, Chen J, Cheng JQ (2004) Aurora-A abrogation of p53 DNA binding and transactivation activity by phosphorylation of serine 215. J Biol Chem 279(50):52175–52182. doi:10.1074/jbc.M406802200 Rohatgi R, Milenkovic L, Scott MP (2007) Patched1 regulates hedgehog signaling at the primary cilium. Science 317(5836):372–376. doi:10.1126/science.1139740 Berbari NF, O’Connor AK, Haycraft CJ, Yoder BK (2009) The primary cilium as a complex signaling center. Curr Biol 19(13):R526–R535. doi:10.1016/j.cub.2009.05.025 Huangfu D, Anderson KV (2005) Cilia and Hedgehog responsiveness in the mouse. Proc Natl Acad Sci USA 102(32):11325–11330. doi:10.1073/pnas.0505328102 Hui CC, Angers S (2011) Gli proteins in development and disease. Annu Rev Cell Dev Biol 27:513–537. doi:10.1146/annurev-cellbio-092910-154048 Wallingford JB, Mitchell B (2011) Strange as it may seem: the many links between Wnt signaling, planar cell polarity, and cilia. Genes Dev 25(3):201–213. doi:10.1101/gad.2008011 Lancaster MA, Schroth J, Gleeson JG (2011) Subcellular spatial regulation of canonical Wnt signalling at the primary cilium. Nat Cell Biol 13(6):700–707. doi:10.1038/ncb2259 Lancaster MA, Gopal DJ, Kim J, Saleem SN, Silhavy JL, Louie CM, Thacker BE, Williams Y, Zaki MS, Gleeson JG (2011) Defective Wnt-dependent cerebellar midline fusion in a mouse model of Joubert syndrome. Nat Med 17(6):726–731. doi:10.1038/nm.2380 Mix LL, Dinerstein RJ, Villereal ML (1984) Mitogens and melittin stimulate an increase in intracellular free calcium concentration in human fibroblasts. Biochem Biophys Res Commun 119(1):69–75. doi:10.1016/0006-291X(84)91619-X McNeil PL, McKenna MP, Taylor DL (1985) A transient rise in cytosolic calcium follows stimulation of quiescent cells with growth factors and is inhibitable with phorbol myristate acetate. J Cell Biol 101(2):372–379. doi:10.1083/jcb.101.2.372 Tucker RW, Chang DT, Meade-Cobun K (1989) Effects of platelet-derived growth factor and fibroblast growth factor on free intracellular calcium and mitogenesis. J Cell Biochem 39(2):139–151. doi:10.1002/jcb.240390206 Plotnikova OV, Pugacheva EN, Dunbrack RL, Golemis EA (2010) Rapid calcium-dependent activation of Aurora-A kinase. Nat Commun 1(6):1–8. doi:10.1038/ncomms1061 Lee KH, Johmura Y, Yu LR, Park JE, Gao Y, Bang JK, Zhou M, Veenstra TD, Yeon Kim B, Lee KS (2012) Identification of a novel Wnt5a–CK1ε–Dvl2–Plk1-mediated primary cilia disassembly pathway. EMBO J 31(14):3104–3117. doi:10.1038/emboj.2012.144 Archambault V, Glover DM (2009) Polo-like kinases: conservation and divergence in their functions and regulation. Nat Rev Mol Cell Biol 10(4):265–275. doi:10.1038/nrm2653 Barr FA, Sillje HH, Nigg EA (2004) Polo-like kinases and the orchestration of cell division. Nat Rev Mol Cell Biol 5(6):429–440. doi:10.1038/nrm1401 Petronczki M, Lenart P, Peters JM (2008) Polo on the rise-from mitotic entry to cytokinesis with Plk1. Dev Cell 14(5):646–659. doi:10.1016/j.devcel.2008.04.014 Seeger-Nukpezah T, Liebau MC, Hopker K, Lamkemeyer T, Benzing T, Golemis EA, Schermer B (2012) The centrosomal kinase plk1 localizes to the transition zone of primary cilia and induces phosphorylation of nephrocystin-1. PLoS ONE 7(6):e38838. doi:10.1371/journal.pone.0038838 Xu J, Li H, Wang B, Xu Y, Yang J, Zhang X, Harten SK, Shukla D, Maxwell PH, Pei D, Esteban MA (2010) VHL inactivation induces HEF1 and Aurora kinase A. J Am Soc Nephrol 21(12):2041–2046. doi:10.1681/ASN.2010040345 Barakat MT, Scott MP (2009) Tail wags dog: primary cilia and tumorigenesis. Cancer Cell 16(4):276–277. doi:10.1016/j.ccr.2009.09.019 Han YG, Kim HJ, Dlugosz AA, Ellison DW, Gilbertson RJ, Alvarez-Buylla A (2009) Dual and opposing roles of primary cilia in medulloblastoma development. Nat Med 15(9):1062–1065. doi:10.1038/nm.2020 Moser JJ, Fritzler MJ, Rattner JB (2009) Primary ciliogenesis defects are associated with human astrocytoma/glioblastoma cells. BMC Cancer 9:448. doi:10.1186/1471-2407-9-448 Schraml P, Frew IJ, Thoma CR, Boysen G, Struckmann K, Krek W, Moch H (2009) Sporadic clear cell renal cell carcinoma but not the papillary type is characterized by severely reduced frequency of primary cilia. Mod Pathol 22(1):31–36. doi:10.1038/modpathol.2008.132 Seeley ES, Carriere C, Goetze T, Longnecker DS, Korc M (2009) Pancreatic cancer and precursor pancreatic intraepithelial neoplasia lesions are devoid of primary cilia. Cancer Res 69(2):422–430. doi:10.1158/0008-5472.CAN-08-1290 Wong SY, Seol AD, So PL, Ermilov AN, Bichakjian CK, Epstein EH Jr, Dlugosz AA, Reiter JF (2009) Primary cilia can both mediate and suppress Hedgehog pathway-dependent tumorigenesis. Nat Med 15(9):1055–1061. doi:10.1038/nm.2011 Bischoff JR, Anderson L, Zhu Y, Mossie K, Ng L, Souza B, Schryver B, Flanagan P, Clairvoyant F, Ginther C, Chan CS, Novotny M, Slamon DJ, Plowman GD (1998) A homologue of Drosophila aurora kinase is oncogenic and amplified in human colorectal cancers. EMBO J 17(11):3052–3065. doi:10.1093/emboj/17.11.3052 Katayama H, Brinkley WR, Sen S (2003) The Aurora kinases: role in cell transformation and tumorigenesis. Cancer Metastasis Rev 22(4):451–464. doi:10.1023/A:1023789416385 Dippell RV (1968) The development of basal bodies in paramecium. Proc Natl Acad Sci USA 61(2):461–468 Schmidt KN, Kuhns S, Neuner A, Hub B, Zentgraf H, Pereira G (2012) Cep164 mediates vesicular docking to the mother centriole during early steps of ciliogenesis. J Cell Biol 199(7):1083–1101. doi:10.1083/jcb.201202126 Rompolas P, Pedersen LB, Patel-King RS, King SM (2007) Chlamydomonas FAP133 is a dynein intermediate chain associated with the retrograde intraflagellar transport motor. J Cell Sci 120(Pt 20):3653–3665. doi:10.1242/jcs.012773