Skip to main content
SpringerLink
Log in

Show me your license, please: deregulation of centriole duplication mechanisms that promote amplification

  • Review
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

Centrosomes are organelles involved in generating and organizing the interphase microtubule cytoskeleton, mitotic spindles and cilia. At the centrosome core are a pair of centrioles, structures that act as the duplicating elements of this organelle. Centrioles function to recruit and organize pericentriolar material which nucleates microtubules. While centrioles are relatively simple in construction, the mechanics of centriole biogenesis remain an important yet poorly understood process. More mysterious still are the regulatory mechanisms that oversee centriole assembly. The fidelity of centriole duplication is critical as defects in either the assembly or number of centrioles promote aneuploidy, primary microcephaly, birth defects, ciliopathies and tumorigenesis. In addition, some pathogens employ mechanisms to promote centriole overduplication to the detriment of the host cell. This review summarizes our current understanding of this important topic, highlighting the need for further study if new therapeutics are to be developed to treat diseases arising from defects of centrosome duplication.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

APC:

Anaphase-promoting complex

Asl:

Asterless protein

PCM:

Pericentriolar material

Plk4:

Polo-like kinase 4

PP2A:

Protein phosphatase 2A

pre-RC:

Pre-replication complex

ST:

Small tumor antigen

SV40:

Simian virus 40

References

  1. Song MH, Miliaras NB, Peel N, O’Connell KF (2008) Centrioles: some self-assembly required. Curr Opin Cell Biol 20:688–693

    Article  PubMed  CAS  Google Scholar 

  2. Nigg EA (2007) Centrosome duplication: of rules and licenses. Trends Cell Biol 17(215):221

    Google Scholar 

  3. Ganem NJ, Godinho SA, Pellman D (2009) A mechanism linking extra centrosomes to chromosomal instability. Nature 460:278–282

    Article  PubMed  CAS  Google Scholar 

  4. Silkworth WT, Nardi IK, Scholl LM, Cimini D (2009) Multipolar spindle pole coalescence is a major source of kinetochore mis-attachment and chromosome mis- segregation in cancer cells. PLoS One 4:e6564

    Article  PubMed  CAS  Google Scholar 

  5. Crasta K, Ganem NJ, Dagher R, Lantermann AB, Ivanova EV, Pan Y, Nezi L, Protopopov A, Chowdhury D, Pellman D (2012) DNA breaks and chromosome pulverization from errors in mitosis. Nature 482:53–58

    Article  PubMed  CAS  Google Scholar 

  6. Storchova Z, Pellman D (2004) From polyploidy to aneuploidy, genome instability and cancer. Nat Rev Mol Cell Biol 5:45–54

    Article  PubMed  CAS  Google Scholar 

  7. Pellman D (2007) Aneuploidy and cancer. Nature 446:38–39

    Article  PubMed  CAS  Google Scholar 

  8. Pihan GA, Wallace J, Zhou Y, Doxsey SJ (2003) Centrosome abnormalities and chromosome instability occur together in pre-invasive carcinomas. Cancer Res 63:1398–1404

    PubMed  CAS  Google Scholar 

  9. Rusan NM, Peifer M (2007) A role for a novel centrosome cycle in asymmetric cell division. J Cell Biol 177:13–20

    Article  PubMed  CAS  Google Scholar 

  10. Castellanos E, Dominguez P, Gonzalez C (2008) Centrosome dysfunction in Drosophila neural stem cells causes tumors that are not due to genome instability. Curr Biol 18:1209–1214

    Article  PubMed  CAS  Google Scholar 

  11. Basto R, Brunk K, Vinadogrova T, Peel N, Franz A, Khodjakov A, Raff JW (2008) Centrosome amplification can initiate tumorigenesis in flies. Cell 133:1032–1042

    Article  PubMed  CAS  Google Scholar 

  12. Basto R, Lau J, Vinogradova T, Gardiol A, Woods CG, Khodjakov A, Raff JW (2006) Flies without centrioles. Cell 125:1375–1386

    Article  PubMed  CAS  Google Scholar 

  13. Delaval B, Doxsey S (2008) Dwarfism, where pericentrin gains stature. Science 319:732–733

    Article  PubMed  CAS  Google Scholar 

  14. Delaval B, Doxsey SJ (2010) Pericentrin in cellular function and disease. J Cell Biol 188:181–190

    Article  PubMed  CAS  Google Scholar 

  15. Simons M, Walz G (2006) Polycystic kidney disease: cell division without a c(l)ue? Kidney Int 70:854–864

    Article  PubMed  CAS  Google Scholar 

  16. Kochanski RS, Borisy GG (1990) Mode of centriole duplication and distribution. J Cell Biol 110:1599–1605

    Article  PubMed  CAS  Google Scholar 

  17. Riparbelli MG, Callaini G (2003) Drosophila parthenogenesis: a model for de novo centrosome assembly. Dev Biol 260:298–313

    Article  PubMed  CAS  Google Scholar 

  18. Riparbelli MG, Stouthamer R, Dallai R, Callaini G (1998) Microtubule organization during the early development of the parthenogenetic egg of the hymenopteran Muscidifurax uniraptor. Dev Biol 19:589–599

    Google Scholar 

  19. Ferree PM, McDonald K, Fasulo B, Sullivan W (2006) The origin of centrosomes in parthenogenetic hymenopteran insects. Curr Biol 16:801–807

    Article  PubMed  CAS  Google Scholar 

  20. Peel N, Stevens NR, Basto R, Raff JW (2007) Overexpressing centriole replication proteins in vivo induces centriole overduplication and de novo formation. Curr Biol 17:834–843

    Article  PubMed  CAS  Google Scholar 

  21. Khodjakov A, Rieder CL, Sluder G, Cassels G, Sibon O, Wang CL (2002) De novo formation of centrosomes in vertebrate cells arrested during S phase. J Cell Biol 158:1171–1181

    Article  PubMed  CAS  Google Scholar 

  22. Rodrigues-Martins A, Riparbelli M, Callaini G, Glover DM, Bettencourt-Dias M (2007) Revisiting the role of the mother centriole in centriole biogenesis. Science 316:1046–1050

    Article  PubMed  CAS  Google Scholar 

  23. Dirksen ER (1991) Centriole and basal body formation during ciliogenesis revisited. Biol Cell 72:31–38

    Article  PubMed  CAS  Google Scholar 

  24. Kallenbach RJ, Mazia D (1982) Origin and maturation of centrioles in association with the nuclear envelope in hypertonic-stressed sea urchin eggs. Eur J Cell Biol 28:68–76

    PubMed  CAS  Google Scholar 

  25. Anderson RG, Brenner RM (1971) The formation of basal bodies (centrioles) in the Rhesus monkey oviduct. J Cell Biol 50:10–34

    Article  PubMed  CAS  Google Scholar 

  26. Kuriyama R, Borisy GG (1981) Centriole cycle in Chinese hamster ovary cells as determined by whole-mount electron microscopy. J Cell Biol 91:814–821

    Article  PubMed  CAS  Google Scholar 

  27. Robbins E, Jentzsch G, Micali A (1968) The centriole cycle in synchronized HeLa cells. J Cell Biol 36:329–339

    Article  PubMed  CAS  Google Scholar 

  28. Vorobjev IA, Chentsov YuS (1982) Centrioles in the cell cycle, I. Epithelial cells. J Cell Biol 93:938–949

    Article  PubMed  CAS  Google Scholar 

  29. Alvey PL (1985) An investigation of the centriole cycle using 3T3 and CHO cells. J Cell Sci 78:147–162

    PubMed  CAS  Google Scholar 

  30. Pelletier L, O’Toole E, Schwager A, Hyman AA, Muller-Reichert T (2006) Centriole assembly in Caenorhabditis elegans. Nature 444:619–623

    Article  PubMed  CAS  Google Scholar 

  31. Leidel S, Delattre M, Cerutti L, Baumer K, Gonczy P (2005) SAS-6 defines a protein family required for centrosome duplication in C. elegans and in human cells. Nat Cell Biol 7:115–125

    Article  PubMed  CAS  Google Scholar 

  32. Dammerman A, Muller-Reichert T, Pelletier L, Habermann B, Desai A, Oegema K (2004) Centriole assembly requires both centriolar and pericentriolar material proteins. Dev Cell 7:815–829

    Article  Google Scholar 

  33. Nakazawa Y, Hiraki M, Kamiya R, Hirono M (2007) SAS-6 is a cartwheel protein that establishes the 9-fold symmetry of the centriole. Curr Biol 17:2169–2174

    Article  PubMed  CAS  Google Scholar 

  34. van Breugel M, Hirono M, Andreeva A, Yanagisawa HA, Yamaguchi S, Nakazawa Y, Morgner N, Petrovich M, Ebong IO, Robinson CV, Johnson CM, Veprintsev D, Zuber B (2011) Structures of SAS-6 suggest its organization in centrioles. Science 331:1196–1199

    Article  PubMed  CAS  Google Scholar 

  35. Kitagawa D, Vakonakis I, Olieric N, Hilbert M, Keller D, Olieric V, Bortfeld M, Erat MC, Fluckiger I, Gonczy P (2011) Structural basis of the 9-fold symmetry of centrioles. Cell 144:364–375

    Article  PubMed  CAS  Google Scholar 

  36. Hiraki M, Nakazawa Y, Kamiya R, Hirono M (2007) Bld10p constitutes the cartwheel-spoke tip and stabilizes the 9-fold symmetry of the centriole. Curr Biol 17:1778–1783

    Article  PubMed  CAS  Google Scholar 

  37. Delattre M, Leidel S, Wani K, Baumer K, Bamat J, Schnabel H, Feichtinger R, Schnabel R, Gonczy P (2004) Centriolar SAS-5 is required for centrosome duplication in C. elegans. Nat Cell Biol 6:656–664

    Article  PubMed  CAS  Google Scholar 

  38. Stevens NR, Dobbelaere J, Brunk K, Franz A, Raff JW (2010) Drosophila Ana2 is a conserved centriole duplication factor. J Cell Biol 188:313–323

    Article  PubMed  CAS  Google Scholar 

  39. Stevens NR, Roque H, Raff JW (2010) Sas-6 and Ana2 coassemble into tubules to promote centriole duplication and engagement. Dev Cell 19:913–919

    Article  PubMed  CAS  Google Scholar 

  40. Leidel S, Gonczy P (2003) SAS-4 is essential for centrosome duplication in C. elegans and is recruited to daughter centrioles once per cell cycle. Dev Cell 4:431–439

    Article  PubMed  CAS  Google Scholar 

  41. Kirkham M, Muller-Reichert T, Oegema K, Grill S, Hyman AA (2003) SAS-4 is a C. elegans centriolar protein that controls centrosome size. Cell 112:575–587

    Article  PubMed  CAS  Google Scholar 

  42. Kohlmaier G, Loncarek J, Meng X, McEwen BF, Mogensen MM, Spektor A, Dynlacht BD, Khodjakov A, Gonczy P (2009) Overly long centrioles and defective cell division upon excess of the SAS-4-related protein CPAP. Curr Biol 19:1012–1018

    Article  PubMed  CAS  Google Scholar 

  43. Gopalakrishnan J, Mennella V, Blachon S, Zhai B, Smith AH, Megraw TL, Nicastro D, Gygi SP, Agard DA, Avidor-Reiss T (2011) Sas-4 provides a scaffold for cytoplasmic complexes and tethers them in a centrosome. Nat Commun 2:359. doi:10.1038/ncomms1367

    Google Scholar 

  44. Kleylein-Sohn J, Westendorf J, Le Clech M, Habedanck R, Stierhof YD, Nigg EA (2007) Plk4-induced centriole biogenesis in human cells. Dev Cell 13:190–202

    Article  PubMed  CAS  Google Scholar 

  45. Spektor A, Tsang WY, Khoo D, Dynlacht BD (2007) Cep97 and CP110 suppress a cilia assembly program. Cell 130:678–690

    Article  PubMed  CAS  Google Scholar 

  46. Chen Z, Indjeian VB, McManus M, Wang L, Dynlacht BD (2002) CP110, a cell cycle-dependent CDK substrate, regulates centrosome duplication in human cells. Dev Cell 3:339–350

    Article  PubMed  CAS  Google Scholar 

  47. Schmidt TI, Kleylein-Sohn J, Westendorf J, Le Clech M, Lavoie SB, Stierhof YD, Nigg EA (2009) Control of centriole length by CPAP and CP110. Curr Biol 19:1005–1011

    Article  PubMed  CAS  Google Scholar 

  48. Singla V, Romaguera-Ros M, Garcia-Verdugo JM, Reiter JF (2010) Ofd1, a human disease gene, regulates the length and distal structure of centrioles. Dev Cell 18:410–424

    Article  PubMed  CAS  Google Scholar 

  49. Kobayashi T, Dynlacht BD (2011) Regulating the transition from centriole to basal body. J Cell Biol 193:435–444

    Article  PubMed  CAS  Google Scholar 

  50. Hannak E, Kirkham M, Hyman AA, Oegema K (2001) Aurora-A kinase is required for centrosome maturation in Caenorhabditis elegans. J Cell Biol 155:1109–1116

    Article  PubMed  CAS  Google Scholar 

  51. Berdnik D, Knoblich JA (2002) Drosophila Aurora-A is required for centrosome maturation and actin-dependent asymmetric protein localization during mitosis. Curr Biol 12:640–647

    Article  PubMed  CAS  Google Scholar 

  52. Lane HA, Nigg EA (1996) Antibody microinjection reveals an essential role for human polo-like kinase 1 (Plk1) in the functional maturation of mitotic centrosomes. J Cell Biol 135:1701–1713

    Article  PubMed  CAS  Google Scholar 

  53. Loncarek J, Hergert P, Magidson V, Khodjakov A (2008) Control of daughter centriole formation by the pericentriolar material. Nat Cell Biol 103:22–28

    Google Scholar 

  54. Tsou MF, Wang WJ, George KA, Uryu K, Stearns T, Jallepalli PV (2009) Polo kinase and separase regulate the mitotic licensing of centriole duplication in human cells. Dev Cell 17:344–354

    Article  PubMed  CAS  Google Scholar 

  55. Loncarek J, Hergert P, Khodjakov A (2010) Centriole reduplication during prolonged interphase requires procentriole maturation governed by Plk1. Curr Biol 20:1277–1282

    Article  PubMed  CAS  Google Scholar 

  56. Wang WJ, Soni RK, Uryu K, Tsou MF (2011) The conversion of centrioles to centrosomes: essential coupling of duplication with segregation. J Cell Biol 193:727–739

    Article  PubMed  CAS  Google Scholar 

  57. Wu ZQ, Liu X (2008) Role for Plk1 phosphorylation of Hbo1 in regulation of replication licensing. Proc Natl Acad Sci USA 105:1919–1924

    Article  PubMed  CAS  Google Scholar 

  58. Blow JJ, Dutta A (2005) Preventing re-replication of chromosomal DNA. Nat Rev Mol Cell Biol 6:476–486

    Article  PubMed  CAS  Google Scholar 

  59. DePamphilis ML, Blow JJ, Ghosh S, Saha T, Noguchi K, Vassilev A (2006) Regulating the licensing of DNA replication origins in metazoa. Curr Opin Cell Biol 18:231–239

    Article  PubMed  CAS  Google Scholar 

  60. Machida YJ, Hamlin JL, Dutta A (2005) Right place, right time, and only once: replication initiation in metazoans. Cell 12:313–324

    Google Scholar 

  61. Wong C, Stearns T (2003) Centrosome number is controlled by a centrosome-intrinsic block to reduplication. Nat Cell Biol 5:539–544

    Article  PubMed  CAS  Google Scholar 

  62. Tsou MF, Stearns T (2006) Mechanism limiting centrosome duplication to once per cell cycle. Nature 442:947–951

    Article  PubMed  CAS  Google Scholar 

  63. Hinchcliffe EH, Li C, Thompson EA, Maller JL, Sluder G (1999) Requirement of Cdk2–cyclin E activity for repeated centrosome reproduction in Xenopus egg extracts. Science 283:851–854

    Article  PubMed  CAS  Google Scholar 

  64. Lacey KR, Jackson PK, Stearns T (1999) Cyclin-dependent kinase control of centrosome duplication. Proc Natl Acad Sci USA 96:2817–2822

    Article  PubMed  CAS  Google Scholar 

  65. Matsumoto Y, Hayashi K, Nishida E (1999) Cyclin-dependent kinase 2 (Cdk2) is required for centrosome duplication in mammalian cells. Curr Biol 9:429–432

    Article  PubMed  CAS  Google Scholar 

  66. Meraldi P, Lukas J, Fry AM, Bartek J, Nigg EA (1999) Centrosome duplication in mammalian somatic cells requires E2F and Cdk2-cyclin A. Nat Cell Biol 1:88–93

    Article  PubMed  CAS  Google Scholar 

  67. Okuda M, Horn HF, Tarapore P, Tokuyama Y, Smulian AG, Chan PK, Knudsen ES, Hofmann IA, Snyder JD, Bove KE, Fukasawa K (2000) Nucleophosmin/B23 is a target of CDK2-cyclin E in centrosome duplication. Cell 103:127–140

    Article  PubMed  CAS  Google Scholar 

  68. Fisk HA, Winey A (2001) The mouse Mps1p-like kinase regulates centrosome duplication. Cell 106:95–104

    Article  PubMed  CAS  Google Scholar 

  69. Fisk HA, Mattison CP, Winey M (2003) Human Mps1 protein kinase is required for centrosome duplication and normal mitotic progression. Proc Natl Acad Sci USA 100:14875–14880

    Article  PubMed  CAS  Google Scholar 

  70. Kasbek C, Yang CH, Yusof AM, Chapman HM, Winey M, Fisk HA (2007) Preventing the degradation of mps1 at centrosomes is sufficient to cause centrosome reduplication in human cells. Mol Biol Cell 18:4457–4469

    Article  PubMed  CAS  Google Scholar 

  71. Shinmura K, Tarapore P, Tokuyama Y, George KR, Fukasawa K (2005) Characterization of centrosomal association of nucleophosmin/B23 linked to Crm1 activity. FEBS Lett 579:6621–6634

    Article  PubMed  CAS  Google Scholar 

  72. Duensing A, Liu Y, Tseng M, Malumbres M, Barbacid M, Duensing S (2006) Cyclin-dependent kinase 2 is dispensable for normal centrosome duplication but required for oncogene-induced centrosome overduplication. Oncogene 252:943–949

    Google Scholar 

  73. Matsumoto Y, Maller JL (2002) Calcium, calmodulin, and CaMKII requirement for initiation of centrosome duplication in Xenopus egg extracts. Science 29:5499–5502

    Google Scholar 

  74. Hinchcliffe EH, Cassels GO, CL Rieder, Sluder G (1998) The coordination of centrosome reproduction with nuclear events of the cell cycle in the sea urchin zygote. J Cell Biol 140:1417–1426

    Article  PubMed  CAS  Google Scholar 

  75. Tsou MF, Stearns T (2006) Controlling centrosome number: licenses and blocks. Curr Opin Cell Biol 18:74–78

    Article  PubMed  CAS  Google Scholar 

  76. O’Connell BC, Harper JW (2007) Ubiquitin proteasome system (UPS): what can chromatin do for you? Curr Opin Cell Biol 19:206–214

    Article  PubMed  CAS  Google Scholar 

  77. Ferenbach A, Li A, Brito-Martins M, Blow JJ (2005) Functional domains of the Xenopus replication licensing factor CDT. Nucleic Acids Res 33:316–324

    Article  PubMed  CAS  Google Scholar 

  78. Wei Z, Liu C, Wu X, Xu N, Zhou B, Liang C, Zhu G (2010) Characterization and structure determination of the Cdt1 binding domain of human minichromosome maintenance (Mcm) 6. J Biol Chem 285:12469–12473

    Article  PubMed  CAS  Google Scholar 

  79. Nakamura A, Arai H, Fujita N (2009) Centrosomal Aki1 and cohesion function in separase-regulated centriole disengagement. J Cell Biol 187:607–614

    Article  PubMed  CAS  Google Scholar 

  80. Schöckel L, Möckel M, Mayer B, Boos D, Stemmann O (2011) Cleavage of cohesin rings coordinates the separation of centrioles and chromatids. Nat Cell Biol 13:966–972

    Article  PubMed  CAS  Google Scholar 

  81. Balczon R, Bao L, Zimmer WE, Brown K, Zinkowski RP, Brinkley BR (1995) Dissociation of centrosome replication events from cycles of DNA synthesis and mitotic division in hydroxyurea-arrested Chinese hamster ovary cells. J Cell Biol 130:105–115

    Article  PubMed  CAS  Google Scholar 

  82. Habedanck R, Stierhof YD, Wilkinson CJ, Nigg EA (2005) The Polo kinase Plk4 functions in centriole duplication. Nat Cell Biol 71:140–146

    Google Scholar 

  83. Duensing A, Liu Y, Perdreau SA, Kleylein-Sohn J, Nigg EA, Duensing S (2007) Centriole overduplication through the concurrent formation of multiple daughter centrioles at single maternal templates. Oncogene 26:6280–6288

    Article  PubMed  CAS  Google Scholar 

  84. Strnad P, Leidel S, Vinogradova T, Euteneuer U, Khodjakov A, Gönczy P (2007) Regulated HsSAS-6 levels ensure formation of a single procentriole per centriole during the centrosome duplication cycle. Dev Cell 13:203–213

    Article  PubMed  CAS  Google Scholar 

  85. Korzeniewski N, Zheng L, Cuevas R, Parry J, Chatterjee P, Anderton B, Duensing A, Münger K, Duensing S (2009) Cullin 1 functions as a centrosomal suppressor of centriole multiplication by regulating polo-like kinase 4 protein levels. Cancer Res 69:6668–6675

    Article  PubMed  CAS  Google Scholar 

  86. Cunha-Ferreira I, Rodrigues-Martins A, Bento I, Riparbelli M, Zhang W, Laue E, Callaini G, Glover DM, Bettencourt-Dias M (2009) The SCF/Slimb ubiquitin ligase limits centrosome amplification through degradation of SAK/PLK4. Curr Biol 19:43–49

    Article  PubMed  CAS  Google Scholar 

  87. Rogers GC, Rusan NM, Roberts DM, Peifer M, Rogers SL (2009) The SCF Slimb ubiquitin ligase regulates Plk4/Sak levels to block centriole reduplication. J Cell Biol 184:225–239

    Article  PubMed  CAS  Google Scholar 

  88. Fode C, Motro B, Yousefi S, Heffernan M, Dennis JW (1994) Sak, a murine protein-serine/threonine kinase that is related to the Drosophila polo kinase and involved in cell proliferation. Proc Natl Acad Sci USA 91:6388–6392

    Article  PubMed  CAS  Google Scholar 

  89. Bettencourt-Dias M, Rodrigues-Martins A, Carpenter L, Riparbelli M, Lehmann L, Gatt MK, Carmo N, Balloux F, Callaini G, Glover DM (2005) SAK/PLK4 is required for centriole duplication and flagella development. Curr Biol 152:199–207

    Google Scholar 

  90. Brownlee CW, Klebba JE, Buster DW, Rogers GC (2011) The protein phosphatase 2A regulatory subunit twins stabilizes Plk4 to induce centriole amplification. J Cell Biol 195:231–243

    Article  PubMed  CAS  Google Scholar 

  91. O’Connell KF, Caron C, Kopish KR, Hurd DD, Kemphues KJ, Li Y, White JG (2001) The C. elegans zyg-1 gene encodes a regulator of centrosome duplication with distinct maternal and paternal roles in the embryo. Cell 105:547–558

    Article  PubMed  Google Scholar 

  92. Delattre M, Canard C, Gönczy P (2006) Sequential protein recruitment in C. elegans centriole formation. Curr Biol 16:1844–1849

    Article  PubMed  CAS  Google Scholar 

  93. Kitagawa D, Busso C, Fluckiger I, Gönczy P (2009) Phosphorylation of SAS-6 by ZYG-1 is critical for centriole formation in C. elegans embryos. Dev Cell 17:900–907

    Article  PubMed  CAS  Google Scholar 

  94. Puklowski A, Homsi Y, Keller D, May M, Chauhan S, Kossatz U, Grunwald V, Kubicka S, Pich A, Manns MP et al (2011) The SCF-FBXW5 E3-ubiquitin ligase is regulated by PLK4 and targets HsSAS-6 to control centrosome duplication. Nat Cell Biol 13:1004–1009

    Article  PubMed  CAS  Google Scholar 

  95. Blachon S, Gopalakrishnan J, Omori Y, Polyanovsky A, Church A, Nicastro D, Malicki J, Avidor-Reiss T (2008) Drosophila asterless and vertebrate Cep152 Are orthologs essential for centriole duplication. Genetics 180:2081–2094

    Article  PubMed  CAS  Google Scholar 

  96. Varmark H, Llamazares S, Rebollo E, Lange B, Reina J, Schwartz H, Gonzalez C (2007) Asterless is a centriolar protein required for centrosome function and embryo development in Drosophila. Curr Biol 17:1735–1745

    Article  PubMed  CAS  Google Scholar 

  97. Cizmecioglu O, Arnold M, Bahtz R, Settele F, Ehret L, Haselmann-Weiss U, Antony C, Hoffmann I (2010) Cep152 acts as a scaffold for recruitment of Plk4 and CPAP to the centrosome. J Cell Biol 191:731–739

    Article  PubMed  CAS  Google Scholar 

  98. Dzhindzhev NS, Yu QD, Weiskopf K, Tzolovsky G, Cunha-Ferreira I, Riparbelli M, Rodrigues-Martins A, Bettencourt-Dias M, Callaini G, Glover DM (2010) Asterless is a scaffold for the onset of centriole assembly. Nature 467:714–718

    Article  PubMed  CAS  Google Scholar 

  99. Hatch EM, Kulukian A, Holland AJ, Cleveland DW, Stearns T (2010) Cep152 interacts with Plk4 and is required for centriole duplication. J Cell Biol 19:721–729

    Article  CAS  Google Scholar 

  100. Leung GC, Ho CS, Blasutig IM, Murphy JM, Sicheri F (2007) Determination of the Plk4/Sak consensus phosphorylation motif using peptide spot arrays. FEBS Lett 581:77–83

    Article  PubMed  CAS  Google Scholar 

  101. Sillibourne JE, Tack F, Vloemans N, Boeckx A, Thambirajah S, Bonnet P, Ramaekers FC, Bornens M, Grand-Perret T (2010) Autophosphorylation of pololike kinase 4 and its role in centriole duplication. Mol Biol Cell 21:547–561

    Article  PubMed  CAS  Google Scholar 

  102. Holland AJ, Lan W, Niessen S, Hoover H, Cleveland DW (2010) Polo-like kinase 4 kinase activity limits centrosome overduplication by autoregulating its own stability. J Cell Biol 188:191–198

    Article  PubMed  CAS  Google Scholar 

  103. Guderian G, Westendorf J, Uldschmid A, Nigg EA (2010) Plk4 transautophosphorylation regulates centriole number by controlling betaTrCP-mediated degradation. J Cell Sci 123:2163–2169

    Article  PubMed  CAS  Google Scholar 

  104. Leung GC, Hudson JW, Kozarova A, Davidson A, Dennis JW, Sicheri F (2002) The Sak polo-box comprises a structural domain sufficient for mitotic subcellular localization. Nat Struct Biol 9:719–724

    Article  PubMed  CAS  Google Scholar 

  105. Song MH, Liu Y, Anderson DE, Jahng WJ, O’Connell KF (2011) Protein phosphatase 2A-SUR-6/B55 regulates centriole duplication in C. elegans by controlling the levels of centriole assembly factors. Dev Cell 20:563–571

    Article  PubMed  CAS  Google Scholar 

  106. Kitagawa D, Fluckiger I, Polanowska J, Keller D, Reboul J, Gönczy P (2011) PP2A phosphatase acts upon SAS-5 to ensure centriole formation in C. elegans embryos. Dev Cell 20:550–562

    Article  PubMed  CAS  Google Scholar 

  107. Fode C, Binkert C, Dennis JW (1996) Constitutive expression of murine Sak-a suppresses cell growth and induces multinucleation. Mol Cell Biol 16:4665–4672

    PubMed  CAS  Google Scholar 

  108. Chang J, Cizmecioglu O, Hoffmann I, Rhee K (2010) PLK2 phosphorylation is critical for CPAP function in procentriole formation during the centrosome cycle. EMBO J 29:2395–2406

    Article  PubMed  CAS  Google Scholar 

  109. Tang CJ, Lin SY, Hsu WB, Lin YN, Wu CT, Lin YC, Chang CW, Wu KS, Tang TK (2011) The human microcephaly protein STIL interacts with CPAP and is required for procentriole formation. EMBO J 30:4790–4804

    Article  PubMed  CAS  Google Scholar 

  110. Arquint C, Sonnen KF, Stierhof YD, Nigg EA (2012) Cell-cycle-regulated expression of STIL controls centriole number in human cells. J Cell Sci 125:1342–1352

    Article  PubMed  CAS  Google Scholar 

  111. Vulprecht J, David A, Tibelius A, Castiel A, Konotop G, Liu F, Bestvater F, Raab MS, Zentgraf H, Izraeli S, Krämer A (2012) STIL is required for centriole duplication in human cells. J Cell Sci 125:1353–1362

    Article  PubMed  CAS  Google Scholar 

  112. Hagiwara H, Ohwada N, Takata K (2004) Cell biology of normal and abnormal ciliogenesis in the ciliated epithelium. Int Rev Cytol 234:101–141

    Article  PubMed  Google Scholar 

  113. La Terra S, English CN, Hergert P, McEwen BF, Sluder G, Khodjakov A (2005) The de novo centriole assembly pathway in HeLa cells: cell cycle progression and centriole assembly/maturation. J Cell Biol 168:713–722

    Article  PubMed  CAS  Google Scholar 

  114. Uetake Y, Loncarek J, Nordberg JJ, English CN, La Terra S, Khodjakov A, Sluder G (2007) Cell cycle progression and de novo centriole assembly after centrosomal removal in untransformed human cells. J Cell Biol 176:173–182

    Article  PubMed  CAS  Google Scholar 

  115. Löffler H, Fechter A, Matuszewska M, Saffrich R, Mistrik M, Marhold J, Hornung C, Westermann F, Bartek J, Krämer A (2011) Cep63 recruits Cdk1 to the centrosome: implications for regulation of mitotic entry, centrosome amplification, and genome maintenance. Cancer Res 71:2129–2139

    Article  PubMed  CAS  Google Scholar 

  116. Sir JH, Barr AR, Nicholas AK, Carvalho OP, Khurshid M, Sossick A, Reichelt S, D’Santos C, Woods CG, Gergely F (2011) A primary microcephaly protein complex forms a ring around parental centrioles. Nat Genet 43:1147–1153

    Article  PubMed  CAS  Google Scholar 

  117. Nakayama K, Nagahama H, Minamishima YA, Matsumoto M, Nakamichi I, Kitagawa K, Shirane M, Tsunematsu R, Tsukiyama T, Ishida N, Kitagawa M, Nakayama K, Hatakeyama S (2000) Targeted disruption of Skp2 results in accumulation of cyclin E and p27 (Kip1), polyploidy and centrosome overduplication. EMBO J 19:2069–2081

    Article  PubMed  CAS  Google Scholar 

  118. Wojcik EJ, Glover DM, Hays TS (2000) The SCF ubiquitin ligase protein slimb regulates centrosome duplication in Drosophila. Curr Biol 10:1131–1134

    Article  PubMed  CAS  Google Scholar 

  119. Guardavaccaro D, Kudo Y, Boulaire J, Barchi M, Busino L, Donzelli M, Margottin-Goguet F, Jackson PK, Yamasaki L, Pagano M (2003) Control of meiotic and mitotic progression by the F box protein beta-Trcp1 in vivo. Dev Cell 4:799–812

    Article  PubMed  CAS  Google Scholar 

  120. Murphy TD (2003) Drosophila skpA, a component of SCF ubiquitin ligase, regulates centrosome duplication independently of cyclin E accumulation. J Cell Sci 116:2321–2332

    Article  PubMed  CAS  Google Scholar 

  121. Wang W, Budhu A, Forgues M, Wang XW (2005) Temporal and spatial control of nucleophosmin by the Ran-Crm1 complex in centrosome duplication. Nat Cell Biol 7:823–830

    Article  PubMed  CAS  Google Scholar 

  122. Ko MJ, Murata K, Hwang DS, Parvin JD (2006) Inhibition of BRCA1 in breast cell lines causes the centrosome duplication cycle to be disconnected from the cell cycle. Oncogene 25:298–303

    Article  PubMed  CAS  Google Scholar 

  123. Sato K, Hayami R, Wu W et al (2004) Nucleophosmin/B23 is a candidate substrate for the BRCA1-BARD1 ubiquitin ligase. J Biol Chem 279:30919–30922

    Article  PubMed  CAS  Google Scholar 

  124. Starita LM, Machida Y, Sankaran S, Elias JE, Griffin K, Schlegel BP, Gygi SP, Parvin JD (2004) BRCA1-dependent ubiquitination of γ-tubulin regulates centrosome number. Mol Cell Biol 24:8457–8466

    Article  PubMed  CAS  Google Scholar 

  125. Shang Y, Tsao CC, Gorovsky MA (2005) Mutational analyses reveal a novel function of the nucleotide-binding domain of gamma-tubulin in the regulation of basal body biogenesis. J Cell Biol 171:1035–1044

    Article  PubMed  CAS  Google Scholar 

  126. Fukasawa K, Choi T, Kuriyama R, Rulong S, Vande Woude GF (1996) Abnormal centrosome amplification in the absence of p53. Science 271:1744–1747

    Article  PubMed  CAS  Google Scholar 

  127. Meraldi P, Honda R, Nigg EA (2002) Aurora-A overexpression reveals tetraploidization as a major route to centrosome amplification in p53−/− cells. EMBO J 21:483–492

    Article  PubMed  CAS  Google Scholar 

  128. Borel F, Lohez OD, Lacroix FB, Margolis RL (2002) Multiple centrosomes arise from tetraploidy checkpoint failure and mitotic centrosome clusters in p53 and RB pocket protein-compromised cells. Proc Natl Acad Sci USA 99:9819–9824

    Article  PubMed  CAS  Google Scholar 

  129. D’Assoro AB, Busby R, Suino K, Delva E, Almodovar–Mercado GJ, Johnson H, Folk C, Farrugia DJ, Vasile V, Stivala F, Salisbury JL (2004) Genotoxic stress leads to centrosome amplification in breast cancer cell lines that have an inactive G1/S cell cycle checkpoint. Oncogene 23:4068–4075

    Article  PubMed  CAS  Google Scholar 

  130. Li J, Tan M, Li L, Pamarthy D, Lawrence TS, Sun Y (2005) SAK, a new polo-like kinase, is transcriptionally repressed by p53 and induces apoptosis upon RNAi silencing. Neoplasia 7:312–323

    Article  PubMed  CAS  Google Scholar 

  131. Mandal S, Freije WA, Guptan P, Banerjee U (2010) Metabolic control of G1-S transition: cyclin E degradation by p53-induced activation of the ubiquitin-proteasome system. J Cell Biol 188:473–479

    Article  PubMed  CAS  Google Scholar 

  132. Hemerly AS, Prasanth SG, Siddiqui K, Stillman B (2009) Orc1 controls centriole and centrosome copy number in human cells. Science 32:3789–3793

    Google Scholar 

  133. Wu J, Cho HP, Rhee DB, Johnson DK, Dunlap J, Liu Y, Wang Y (2008) Cdc14B depletion leads to centriole amplification, and its overexpression prevents unscheduled centriole duplication. J Cell Biol 181:475–483

    Article  PubMed  CAS  Google Scholar 

  134. Lu F, Lan R, Zhang H, Jiang Q, Zhang C (2008) Geminin is partially localized to centrosome and plays a role in proper centrosome duplication. Biol Cell 101:273–285

    Article  CAS  Google Scholar 

  135. Tachibana KE, Gonzalez MA, Guarguaglini G, Nigg EA, Laskey RA (2005) Depletion of licensing inhibitor geminin causes centrosome overduplication and mitotic defects. EMBO Rep 6:1052–1057

    Article  PubMed  CAS  Google Scholar 

  136. Vidwans SJ, Wong ML, O’Farrell PH (2003) Anomalous centriole configurations are detected in Drosophila wing disc cells upon Cdk1 inactivation. J Cell Sci 116:137–143

    Article  PubMed  CAS  Google Scholar 

  137. Saunders W (2005) Centrosomal amplification and spindle multipolarity in cancer cells. Semin Cancer Biol 15:25–32

    Article  PubMed  CAS  Google Scholar 

  138. Cho US, Morrone S, Sablina AA, Arroyo JD, Hahn WC, Xu W (2007) Structural basis of PP2A inhibition by small t antigen. PLoS Biol 5:e202

    Article  PubMed  CAS  Google Scholar 

  139. Arroyo JD, Hahn WC (2005) Involvement of PP2A in viral and cellular transformation. Oncogene 24:7746–7755

    Article  PubMed  CAS  Google Scholar 

  140. Chen Y, Xu Y, Bao Q, Xing Y, Li Z, Lin Z, Stock JB, Jeffrey PD, Shi Y (2007) Structural and biochemical insights into the regulation of protein phosphatase 2A by small t antigen of SV40. Nat Struct Mol Biol 14:527–534

    Article  PubMed  CAS  Google Scholar 

  141. Kotadia S, Kao LR, Comerford SA, Jones RT, Hammer RE, Megraw TL (2008) PP2A-dependent disruption of centrosome replication and cytoskeleton organization in Drosophila by SV40 small tumor antigen. Oncogene 27:6334–6346

    Article  PubMed  CAS  Google Scholar 

  142. Johnson KA, Tan M, Sütterlin C (2009) Centrosome abnormalities during a Chlamydia trachomatis infection are caused by dysregulation of the normal duplication pathway. Cell Microbiol 11:1064–1073

    Article  PubMed  CAS  Google Scholar 

  143. Ingemarsdotter C, Keller D, Beard P (2010) The DNA damage response to non-replicating adeno-associated virus: centriole overduplication and mitotic catastrophe independent of the spindle checkpoint. Virology 400:271–286

    Article  PubMed  CAS  Google Scholar 

  144. Duensing S, Lee LY, Duensing A, Basile J, Piboonniyom S, Gonzalez S, Crum CP, Munger K (2000) The human papillomavirus type 16 E6 and E7 oncoproteins cooperate to induce mitotic defects and genomic instability by uncoupling centrosome duplication from the cell division cycle. Proc Natl Acad Sci USA 97:10002–10007

    Article  PubMed  CAS  Google Scholar 

  145. Scheffner M, Werness BA, Huibregtse JM, Levine AJ, Howley PM (1990) The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell 63:1129–1136

    Article  PubMed  CAS  Google Scholar 

  146. Tabakin-Fix Y, Azran I, Schavinky-Khrapunsky Y, Levy O, Aboud M (2006) Functional inactivation of p53 by human T-cell leukemia virus type 1 Tax protein: mechanisms and clinical implications. Carcinogenesis 27:673–681

    Article  PubMed  CAS  Google Scholar 

  147. Nitta T, Kanai M, Sugihara E, Tanaka M, Sun B, Nagasawa T, Sonoda S, Saya H, Miwa M (2006) Centrosome amplification in adult T-cell leukemia and human T-cell leukemia virus type 1 Tax-induced human T cells. Cancer Sci 97:836–841

    Article  PubMed  CAS  Google Scholar 

  148. Huo TI, Wang XW, Forgues M, Wu CG, Spillare EA, Giannini C, Brechot C, Harris CC (2001) Hepatitis B virus X mutants derived from human hepatocellular carcinoma retain the ability to abrogate p53-induced apoptosis. Oncogene 20:3620–3628

    Article  PubMed  CAS  Google Scholar 

  149. Wang XW, Forrester K, Yeh H, Feitelson MA, Gu JR, Harris CC (1994) Hepatitis B virus X protein inhibits p53 sequence-specific DNA binding, transcriptional activity, and association with transcription factor ERCC3. Proc Natl Acad Sci USA 91:2230–2234

    Article  PubMed  CAS  Google Scholar 

  150. Yun C, Cho H, Kim SJ, Lee JH, Park SY, Chan GK, Cho H (2004) Mitotic aberration coupled with centrosome amplification is induced by hepatitis B virus X oncoprotein via the Ras-mitogen-activated protein/extracellular signal-regulated kinase-mitogen-activated protein pathway. Mol Cancer Res 2:159–169

    PubMed  CAS  Google Scholar 

  151. Mantel C, Braun SE, Reid S, Henegariu O, Liu L, Hangoc G, Broxmeyer HE (1999) p21(cip-1/waf-1) deficiency causes deformed nuclear architecture, centriole overduplication, polyploidy, and relaxed microtubule damage checkpoints in human hematopoietic cells. Blood 93:1390–1398

    PubMed  CAS  Google Scholar 

  152. Korzeniewski N, Treat B, Duensing S (2011) The HPV-16 E7 oncoprotein induces centriole multiplication through deregulation of Polo-like kinase 4 expression. Mol Cancer 10:61

    Article  PubMed  CAS  Google Scholar 

  153. Pim D, Massimi P, Dilworth SM, Banks L (2005) Activation of the protein kinase B pathway by the HPV-16 E7 oncoprotein occurs through a mechanism involving interaction with PP2A. Oncogene 24:7830–7838

    Article  PubMed  CAS  Google Scholar 

  154. De Luca A, Mangiacasale R, Severino A, Malquori L, Baldi A, Palena A, Mileo AM, Lavia P, Paggi MG (2003) E1A deregulates the centrosome cycle in a Ran GTPase-dependent manner. Cancer Res 63:1430–1437

    PubMed  Google Scholar 

Download references

Acknowledgments

We would like to thank Daniel W. Buster for critically reading and editing the manuscript and Rachel D. Brownlee for help with the illustrations. We are grateful for support from the NSF IGERT Training Fellowship to C.W.B., the National Cancer Institute P30 CA23074, and the American Cancer Society IRG 74-001-31, the GI SPORE (NCI/NIH P50 CA95060).

Author information

Authors and Affiliations

  1. Department of Cellular and Molecular Medicine, Arizona Cancer Center, University of Arizona, Tucson, AZ, 85724, USA

    Christopher W. Brownlee & Gregory C. Rogers

Authors
  1. Christopher W. Brownlee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gregory C. Rogers
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gregory C. Rogers.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Brownlee, C.W., Rogers, G.C. Show me your license, please: deregulation of centriole duplication mechanisms that promote amplification. Cell. Mol. Life Sci. 70, 1021–1034 (2013). https://doi.org/10.1007/s00018-012-1102-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-012-1102-6

Keywords

Search

Navigation