PLK4: a link between centriole biogenesis and cancer

References

• Novak B, Kapuy O, Domingo-Sananes MR, et al. Regulated protein kinases and phosphatases in cell cycle decisions. CurrOpin Cell Biol. 2010;22:801–808.
   PubMed Web of Science ®Google Scholar
• Lee SY, Jang C, Lee KA. Polo-like kinases (plks), a key regulator of cell cycle and new potential target for cancer therapy. DevReprod. 2014;18:65–71.
   Google Scholar
• Llamazares S, Moreira A, Tavares A, et al. Polo encodes a protein kinase homolog required for mitosis in Drosophila. Genes Dev. 1991;5:2153–2165.
   PubMed Web of Science ®Google Scholar
• Sunkel CE, Glover DM. Polo, a mitotic mutant of Drosophila displaying abnormal spindle poles. J Cell Sci. 1988 Jan;89:25–38.
   PubMed Web of Science ®Google Scholar
• Kitada K, Johnson AL, Johnston LH, et al. A multicopy suppressor gene of the Saccharomyces cerevisiae G1 cell cycle mutant gene dbf4 encodes a proteinkinase and is identified as CDC5. Mol Cell Biol. 1993;13:4445–4457.
   PubMed Web of Science ®Google Scholar
• Ohkura H, Hagan IM, Glover DM. The conserved Schizosaccharomycespombe kinase plo1, required to form a bipolar spindle, the actin ring, and septum, can drive septum formation in G1 and G2 cells. Genes Dev. 1995;9:1059–1073.
   PubMed Web of Science ®Google Scholar
• Mulvihill DP, Petersen J, Ohkura H, et al. Plo1 kinase recruitment to the spindle pole body and its role in cell division in Schizosaccharomycespombe. MolBiol Cell. 1999;10:2771–2785.
   Web of Science ®Google Scholar
• Ouyang B, Wang Y, Wei D. Caenorhabditiselegans contains structural homologs of human prk and plk. DNA Seq. 1999;10:109–113.
   PubMed Web of Science ®Google Scholar
• Chase D, Golden A, Heidecker G, et al. Caenorhabditiselegans contains a third polo-like kinase gene. DNA Seq. 2000;11:327–334.
   PubMed Web of Science ®Google Scholar
• Duncan PI, Pollet N, Niehrs C, et al. Cloning and characterization of Plx2 and Plx3, two additional Polo-like kinases from Xenopuslaevis. Exp Cell Res. 2001;270:78–87.
   PubMed Web of Science ®Google Scholar
• Kumagai A, Dunphy WG. Purification and molecular cloning of Plx1, a Cdc25-regulatory kinase from Xenopus egg extracts. Science. 1996;273:1377–1380.
   PubMed Web of Science ®Google Scholar
• Ouyang B, Pan H, Lu L, et al. Human Prk is a conserved protein serine/threonine kinase involved in regulating M phasefunctions. J Biol Chem. 1997;272:28646–28651.
   PubMed Web of Science ®Google Scholar
• Simmons DL, Neel BG, Stevens R, et al. Identification of an early-growth-response gene encoding a novel putative protein kinase. Mol CellBiol. 1992;12:4164–4169.
   Web of Science ®Google Scholar
• Clay FJ, McEwen SJ, Bertoncello I, et al. Identification and cloning of a protein kinase-encoding mouse gene, Plk, related to the polo gene of Drosophila. ProcNatlAcadSci U S A. 1993;90:4882–4886.
   PubMed Web of Science ®Google Scholar
• Fode C, Motro B, Yousefi S, et al. Sak, amurine protein-serine/threonine kinase that is related to the Drosophila polo kinase andinvolved in cell proliferation. ProcNatlAcadSci U S A. 1994;91:6388–6392.
   PubMed Web of Science ®Google Scholar
• deCárcer G, Manning G, Malumbres M. From Plk1 to Plk5: functional evolution of polo-like kinases. Cell Cycle. 2011;10:2255–2262.
   PubMed Web of Science ®Google Scholar
• Lowery DM, Lim D, Yaffe MB. Structure and function of Polo-like kinases. Oncogene. 2005;24:248–259.
   PubMed Web of Science ®Google Scholar
• Glover DM, Hagan IM, Tavares AA. Polo-like kinases: a team that plays throughout mitosis. Genes Dev. 1998;12:3777–3787.
   PubMed Web of Science ®Google Scholar
• Kauselmann G, Weiler M, Wulff P, et al. The polo-like protein kinases Fnk and Snk associate with a Ca(2+)- and integrin-binding protein and are regulated dynamically with synaptic plasticity. Embo J. 1999;18:5528–5539.
   PubMed Web of Science ®Google Scholar
• Pak DT, Sheng M. Targeted protein degradation and synapse remodeling by an inducible protein kinase. Science. 2003;302:1368–1373.
   PubMed Web of Science ®Google Scholar
• deCárcer G, Escobar B, Higuero AM, et al. Plk5, a polo box domain-only protein with specific roles in neuron differentiation and glioblastoma suppression. Mol Cell Biol. 2011;31:1225–1239.
   PubMed Web of Science ®Google Scholar
• Lane HA, Nigg EA. Antibody microinjection reveals an essential role for human polo-like kinase 1 (Plk1) in the functional maturation of mitotic centrosomes. J Cell Biol. 1996;135:1701–1713.
   PubMed Web of Science ®Google Scholar
• Abrieu A, Brassac T, Galas S, et al. The Polo-like kinase Plx1 is a component of the MPF amplification loop at the G2/M-phase transition of the cell cycle in Xenopus eggs. J Cell Sci. 1998;111:1751–1757.
   PubMed Web of Science ®Google Scholar
• Arnaud L, Pines J, Nigg EA. GFP tagging reveals human Polo-like kinase 1 at the kinetochore/centromere region of mitotic chromosomes. Chromosoma. 1998;107:424–429.
   PubMed Web of Science ®Google Scholar
• Sumara I, Giménez-Abián JF, Gerlich D, et al. Roles of polo-like kinase 1 in the assembly of functional mitotic spindles. Curr Biol. 2004;14:1712–1722.
   PubMed Web of Science ®Google Scholar
• Godinho S, Tavares AA. A role for Drosophila Polo protein in chromosome resolution and segregation during mitosis. Cell Cycle. 2008;7:2529–2534.
   PubMed Web of Science ®Google Scholar
• Kang YH, Park JE, Yu LR, et al. Self-regulated Plk1 recruitment to kinetochores by the Plk1-PBIP1 interaction is critical for proper chromosome segregation. Mol Cell. 2006;24:409–422.
   PubMed Web of Science ®Google Scholar
• Seong YS, Kamijo K, Lee JS, et al. A spindle checkpoint arrest and a cytokinesis failure by the dominant-negative polo-box domain of Plk1 in U-2 OS cells. J Biol Chem. 2002;277:32282–32293.
   PubMed Web of Science ®Google Scholar
• Petronczki M, Glotzer M, Kraut N, et al. Polo-like kinase 1 triggers the initiation of cytokinesis in human cells by promoting recruitment of the RhoGEF Ect2 to the central spindle. Dev Cell. 2007;12:713–725.
   PubMed Web of Science ®Google Scholar
• Ma S, Charron J, Erikson RL. Role of Plk2 (Snk) in mouse development and cell proliferation. Mol Cell Biol. 2003;23:6936–6943.
   PubMed Web of Science ®Google Scholar
• Zimmerman WC, Erikson RL. Finding Plk3. Cell Cycle. 2007;6:1314–1318.
   PubMed Web of Science ®Google Scholar
• Bahassi el M, Hennigan RF, Myer DL, et al. Cdc25C phosphorylation on serine 191 by Plk3 promotes its nuclear translocation. Oncogene. 2004;23:2658–2663.
   PubMed Web of Science ®Google Scholar
• Wang L, Gao J, Dai W, et al. Activation of Polo-like kinase 3 by hypoxic stresses. J Biol Chem. 2008;283:25928–25935.
   PubMed Web of Science ®Google Scholar
• Bahassi el M, Conn CW, Dl M, et al. Mammalian Polo-like kinase 3 (Plk3) is a multifunctional protein involved in stress response pathways. Oncogene. 2002;21:6633–6640.
   PubMed Web of Science ®Google Scholar
• Xie S, Wu H, Wang Q, et al. Genotoxic stress-induced activation of Plk3 is partly mediated by Chk2. Cell Cycle. 2002;1:424–429.
   PubMed Web of Science ®Google Scholar
• Xie S, Wu H, Wang Q, et al. Plk3 functionally links DNA damage to cell cycle arrest and apoptosis at least in part via the p53 pathway. J Biol Chem. 2001;276:43305–43312.
   PubMed Web of Science ®Google Scholar
• Zitouni S, Nabais C, Jana SC, et al. Polo-like kinases: structural variations lead to multiple functions. Nat Rev Mol Cell Biol. 2014;15:433–452.
   PubMed Web of Science ®Google Scholar
• Carvalho-Santos Z, Machado P, Branco P, et al. Stepwise evolution of the centriole-assembly pathway. J Cell Sci. 2010;123:1414–1426.
   PubMed Web of Science ®Google Scholar
• Rodrigues-Martins A, Riparbelli M, Callaini G, et al. Revisiting the role of the mother centriole in centriole biogenesis. Science. 2007;316:1046–1050.
   PubMed Web of Science ®Google Scholar
• Kleylein-Sohn J, Westendorf J, le Clech M, et al. Plk4-induced centriole biogenesis in human cells. Dev Cell. 2007;13:190–202.
   PubMed Web of Science ®Google Scholar
• Bettencourt-Dias M, Rodrigues-Martins A, Carpenter L, et al. SAK/PLK4 is required for centriole duplication and flagella development. Curr Biol. 2005;15:2199–2207.
   PubMed Web of Science ®Google Scholar
• Hudson JW, Kozarova A, Cheung P, et al. Late mitotic failure in mice lacking Sak, a polo-like kinase. Curr Biol. 2001;11:441–446.
   PubMed Web of Science ®Google Scholar
• Habedanck R, Stierhof YD, Wilkinson CJ, et al. The Polo kinase Plk4 functions in centriole duplication. Nat Cell Biol. 2005;7:1140–1146.
   PubMed Web of Science ®Google Scholar
• Basto R, Brunk K, Vinadogrova T, et al. Centrosome amplification can initiate tumorigenesis in flies. Cell. 2008;133:1032–1042.
   PubMed Web of Science ®Google Scholar
• Holland AJ, Lan W, Niessen S, et al. Polo-like kinase 4 kinase activity limits centrosome overduplication by autoregulating its own stability. J Cell Biol. 2010;188:191–198.
   PubMed Web of Science ®Google Scholar
• Ganem NJ, Godinho SA, Pellman D. A mechanism linking extra centrosomes to chromosomal instability. Nature. 2009;460:278–282.
   PubMed Web of Science ®Google Scholar
• Hudson JW, Chen L, Fode C, et al. Sak kinase gene structure andtranscriptional regulation. Gene. 2000;241:65–73.
   PubMed Web of Science ®Google Scholar
• Sillibourne JE, Bornens M. Polo-like kinase 4: the odd one out of the family. Cell Div. 2010;5:25.
   PubMed Web of Science ®Google Scholar
• Yamashita Y, Kajigaya S, Yoshida K, et al. Sak serine-threonine kinase acts as an effector of Tec tyrosine kinase. J Biol Chem. 2001;276:39012–39020.
   PubMed Web of Science ®Google Scholar
• Klebba JE, Buster DW, McLamarrah TA, et al. Autoinhibition and relief mechanism for Polo-like kinase 4. ProcNatlAcadSci U S A. 2015;112:E657–E666.
   PubMed Web of Science ®Google Scholar
• Slevin LK, Nye J, Pinkerton DC, et al. The structure of the plk4 cryptic polo box reveals two tandem polo boxes required for centriole duplication. Structure. 2012;20:1905–1917.
   PubMed Web of Science ®Google Scholar
• Arquint C, Gabryjonczyk AM, Imseng S, et al. STIL binding to Polo-box 3 of PLK4 regulates centriole duplication. Elife. 2015 18;4.
   PubMed Web of Science ®Google Scholar
• Rechsteiner M, Rogers SW. PEST sequences and regulation by proteolysis. Trends Biochem Sci. 1996;21:267–271.
   PubMed Web of Science ®Google Scholar
• Cunha-Ferreira I, Rodrigues-Martins A, Bento I, et al. The SCF/Slimb ubiquitin ligase limits centrosome amplification through degradation of SAK/PLK4. Curr Biol. 2009;19:43–49.
   PubMed Web of Science ®Google Scholar
• Rogers GC, Rusan NM, Roberts DM, et al. The SCF Slimb ubiquitin ligase regulates Plk4/Sak levels to block centriole reduplication. J Cell Biol. 2009;184:225–239.
   PubMed Web of Science ®Google Scholar
• Shinmura K, Kurabe N, Goto M, et al. PLK4 overexpression and its effect on centrosome regulation and chromosome stability in human gastric cancer. MolBiol Rep. 2014;41:6635–6644.
   PubMed Web of Science ®Google Scholar
• Winkles JA, Alberts GF. Differential regulation of polo-like kinase 1, 2, 3, and 4 gene expression in mammalian cells and tissues. Oncogene. 2005;24:260–266.
   PubMed Web of Science ®Google Scholar
• Fode C, Binkert C, Dennis JW. Constitutive expression of murine Sak-a suppresses cell growth and induces multinucleation. Mol Cell Biol. 1996;16:4665–4672.
   PubMed Web of Science ®Google Scholar
• Sillibourne JE, Tack F, Vloemans N, et al. Autophosphorylation of polo-like kinase 4 and its role in centriole duplication. MolBiol Cell. 2010;21:547–561.
   Web of Science ®Google Scholar
• Karn T, Holtrich U, Wolf G, et al. Human SAK related to the PLK/polo family of cell cycle kinases shows high mRNA expression in testis. Oncol Rep. 1997;4:505–510.
   PubMed Web of Science ®Google Scholar
• Leung GC, Hudson JW, Kozarova A, et al. The Sak polo-box comprises a structural domain sufficient for mitotic subcellular localization. Nat Struct Biol. 2002;9:719–724.
   PubMedGoogle Scholar
• Sonnen KF, Schermelleh L, Leonhardt H, et al. 3D-structured illumination microscopy provides novel insight into architecture of human centrosomes. Biol Open. 2012;1:965–976.
   PubMed Web of Science ®Google Scholar
• Moyer TC, Clutario KM, Lambrus BG, et al. Binding of STIL to Plk4 activates kinase activity to promote centriole assembly. J Cell Biol. 2015;209:863–878.
   PubMed Web of Science ®Google Scholar
• Kratz AS, Barenz F, Richter KT, et al. Plk4-dependent phosphorylation of STIL is required for centriole duplication. Biol Open. 2015;4:370–377.
   PubMed Web of Science ®Google Scholar
• Rosario CO, Kazazian K, Zih FS, et al. A novel role for Plk4 in regulating cell spreading and motility. Oncogene. 2015;34:3441–3451.
   PubMed Web of Science ®Google Scholar
• Jordan PW, Karppinen J, Handel MA. Polo-like kinase is required for synaptonemal complex disassembly and phosphorylation in mouse spermatocytes. J Cell Sci. 2012;125:5061–5072.
   PubMed Web of Science ®Google Scholar
• Robbins E, Jentzsch G, Micali A. The centriole cycle in synchronized HeLa cells. J Cell Biol. 1968;36:329–339.
   PubMed Web of Science ®Google Scholar
• Chretien D, Buendia B, Fuller SD, et al. Reconstruction of the centrosome cycle from cryoelectron micrographs. J Struct Biol. 1997;120:117–133.
   PubMed Web of Science ®Google Scholar
• Paintrand M, Moudjou M, Delacroix H, et al. Centrosome organization and centriole architecture: their sensitivity to divalent cations. J Struct Biol. 1992;108:107–128.
   PubMed Web of Science ®Google Scholar
• Vorobjev IA, Chentsov Y. Centrioles in the cell cycle. I. Epithelial cells. J Cell Biol. 1982;93:938–949.
   PubMed Web of Science ®Google Scholar
• Kuriyama R, Borisy GG. Centriole cycle in Chinese hamster ovary cells as determined by whole-mount electron microscopy. J Cell Biol. 1981;91:814–821.
   PubMed Web of Science ®Google Scholar
• Rattner JB, Phillips SG. Independence of centriole formation and DNA synthesis. J Cell Biol. 1973;57:359–372.
   PubMed Web of Science ®Google Scholar
• Kim TS, Park JE, Shukla A, et al. Hierarchical recruitment of Plk4 and regulation of centriole biogenesis by two centrosomal scaffolds, Cep192 and Cep152. ProcNatlAcadSci U S A. 2013;110:E4849–E4857.
   PubMed Web of Science ®Google Scholar
• Park SY, Park JE, Kim TS, et al. Molecular basis for unidirectional scaffold switching of human Plk4 in centriole biogenesis. Nat StructMol Biol. 2014;21:696–703.
   Google Scholar
• Pelletier L, O’Toole E, Schwager A, et al. Centriole assembly in Caenorhabditiselegans. Nature. 2006;444:619–623.
   PubMed Web of Science ®Google Scholar
• Sonnen KF, Gabryjonczyk AM, Anselm E, et al. Human Cep192 and Cep152 cooperate in Plk4 recruitment and centriole duplication. J Cell Sci. 2013;126:3223–3233.
   PubMed Web of Science ®Google Scholar
• Franck N, Montembault E, Rome P, et al. CDK11(p58) is required for centriole duplication and Plk4 recruitment to mitotic centrosomes. PLoS One. 2011;6:e14600.
   PubMed Web of Science ®Google Scholar
• Strnad P, Leidel S, Vinogradova T, et al. Regulated HsSAS-6 levels ensure formation of a single procentriole per centriole during the centrosome duplication cycle. Dev Cell. 2007;13:203–213.
   PubMed Web of Science ®Google Scholar
• Ohta M, Ashikawa T, Nozaki Y, et al. Direct interaction of Plk4 with STIL ensures formation of a single procentriole per parental centriole. Nat Commun. 2014;5:5267.
   PubMed Web of Science ®Google Scholar
• Dzhindzhev NS, Tzolovsky G, Lipinszki Z, et al. Plk4 phosphorylates Ana2 to trigger Sas6 recruitment and procentriole formation. Curr Biol. 2014;24:2526–2532.
   PubMed Web of Science ®Google Scholar
• Kitagawa D, Vakonakis I, Olieric N, et al. Structural basis of the 9-fold symmetry of centrioles. Cell. 2011;144:364–375.
   PubMed Web of Science ®Google Scholar
• van Breugel M, Hirono M, Andreeva A, et al. Structures of SAS-6 suggest its organization in centrioles. Science. 2011;331:1196–1199.
   PubMed Web of Science ®Google Scholar
• Puklowski A, Homsi Y, Keller D, et al. The SCF-FBXW5 E3-ubiquitin ligase is regulated by PLK4 and targets HsSAS-6 to control centrosome duplication. Nat Cell Biol. 2011;13:1004–1009.
   PubMed Web of Science ®Google Scholar
• Tsang WY, Bossard C, Khanna H, et al. CP110 suppresses primary cilia formation through its interaction with CEP290, a protein deficient in human ciliary disease. Dev Cell. 2008;15:187–197.
   PubMed Web of Science ®Google Scholar
• Lee M, Seo MY, Chang J, et al. PLK4 phosphorylation of CP110 is required for efficient centriole assembly. Cell Cycle. 2017;16:1225–1234.
   PubMed Web of Science ®Google Scholar
• Petretti C, Savoian M, Montembault E, et al. The PITSLRE/CDK11p58 protein kinase promotes centrosome maturation and bipolar spindle formation. EMBO Rep. 2006;7:418–424.
   PubMed Web of Science ®Google Scholar
• Azimzadeh J, Hergert P, Delouvee A, et al. hPOC5 is a centrin-binding protein required for assembly of full-length centrioles. J Cell Biol. 2009;185:101–114.
   PubMed Web of Science ®Google Scholar
• Tsou MF, Stearns T. Mechanism limiting centrosome duplication to once per cell cycle. Nature. 2006;442:947–951.
   PubMed Web of Science ®Google Scholar
• Tsou MF, Wang WJ, George KA, et al. Polo kinase and separase regulate the mitotic licensing of centriole duplication in human cells. Dev Cell. 2009;17:344–354.
   PubMed Web of Science ®Google Scholar
• Piel M, Nordberg J, Euteneuer U, et al. Centrosome-dependent exit of cytokinesis in animal cells. Science. 2001;291:1550–1553.
   PubMed Web of Science ®Google Scholar
• Duensing A, Liu Y, Perdreau SA, et al. Centriole overduplication through the concurrent formation of multiple daughter centrioles at single maternal templates. Oncogene. 2007;26:6280–6288.
   PubMed Web of Science ®Google Scholar
• Petrinac S, Ganuelas ML, Bonni S, et al. Polo-like kinase 4 phosphorylates Chk2. Cell Cycle. 2009;8:327–329.
   PubMed Web of Science ®Google Scholar
• Bartek J, Bartkova J, Lukas J. DNA damage signalling guards against activated oncogenes and tumour progression. Oncogene. 2007;26:7773–7779.
   PubMed Web of Science ®Google Scholar
• Bartek J, Lukas J. Chk1 and Chk2 kinases in checkpoint control and cancer. Cancer Cell. 2003;3:421–429.
   PubMed Web of Science ®Google Scholar
• Coelho PA, Bury L, Sharif B, et al. Spindle formation in the mouse embryo requires Plk4 in the absence of centrioles. Dev Cell. 2013;27:586–597.
   PubMed Web of Science ®Google Scholar
• Courtois A, Schuh M, Ellenberg J, et al. The transition from meiotic to mitotic spindle assembly is gradual during early mammalian development. J Cell Biol. 2012;198:357–370.
   PubMed Web of Science ®Google Scholar
• Gueth-Hallonet C, Antony C, Aghion J, et al. gamma-Tubulin is present in acentriolar MTOCs during early mouse development. J Cell Sci. 1993;105:157–166.
   PubMed Web of Science ®Google Scholar
• Rosario CO, Ko MA, Haffani YZ, et al. Plk4 is required for cytokinesis and maintenance of chromosomal stability. ProcNatlAcadSci U S A. 2010;107:6888–6893.
   PubMed Web of Science ®Google Scholar
• Luo YB, Kim NH. PLK4 is essential for meiotic resumption in mouse oocytes. BiolReprod. 2015;92:101.
   Web of Science ®Google Scholar
• Tanenbaum ME, Medema RH. Cell fate in the Hand of Plk4. Nat Cell Biol. 2007;9:1127–1129.
   PubMed Web of Science ®Google Scholar
• Firulli AB, McFadden DG, Lin Q, et al. Heart and extra-embryonic mesodermal defects in mouse embryos lacking the bHLH transcription factor Hand1. Nat Genet. 1998;18:266–270.
   PubMed Web of Science ®Google Scholar
• Riley P, Anson-Cartwright L, Cross JC. The Hand1 bHLH transcription factor is essential for placentation and cardiac morphogenesis. Nat Genet. 1998;18:271–275.
   PubMed Web of Science ®Google Scholar
• Hori A, Barnouin K, Snijders AP, et al. A non-canonical function of Plk4 in centriolar satellite integrity and ciliogenesis through PCM1 phosphorylation. EMBO Rep. 2016;17:326–337.
   PubMed Web of Science ®Google Scholar
• Veland IR, Awan A, Pedersen LB, et al. Primary cilia and signaling pathways in mammalian development, health and disease. Nephron Physiol. 2009;111:p39–53.
   Google Scholar
• Coelho PA, Bury L, Shahbazi MN, et al. Over-expression of Plk4 induces centrosome amplification, loss of primary cilia and associated tissue hyperplasia in the mouse. Open Biol. 2015;5:150209.
   PubMed Web of Science ®Google Scholar
• Mahjoub MR, Stearns T. Supernumerary centrosomes nucleate extra cilia and compromise primary cilium signaling. Curr Biol. 2012;22:1628–1634.
   PubMed Web of Science ®Google Scholar
• Rimkus TK, Carpenter RL, Qasem S, et al. Targeting the Sonic Hedgehog signaling pathway: review of smoothened and GLI inhibitors. Cancers (Basel). 2016;8:22.
   PubMed Web of Science ®Google Scholar
• Kazazian K, Xu R, Wu H, et al. The Protrusion Protein Polo-like Kinase 4 (PLK4) Enhances Cancer Invasion. Conf:68th Ann Cancer Symp Soc Surg Oncol. 2015;22.
   Google Scholar
• Godinho SA, Picone R, Burute M, et al. Oncogene-like induction of cellular invasion from centrosome amplification. Nature. 2014;510:167–171.
   PubMed Web of Science ®Google Scholar
• Kazazian K, Go C, Wu H, et al. plk4 promotes cancer invasion and metastasis through Arp2/3 Complex Regulation of the Actin Cytoskeleton. Cancer Res. 2017;77:434–447.
   PubMed Web of Science ®Google Scholar
• Ledoux AC, Sellier H, Gillies K, et al. NFκB regulates expression of Polo-like kinase 4. Cell Cycle. 2013;12:3052–3062.
   PubMed Web of Science ®Google Scholar
• Macmillan JC, Hudson JW, Bull S, et al. Comparative expression of the mitotic regulators SAK and PLK in colorectal cancer. Ann SurgOncol. 2001;8:729–740.
   Google Scholar
• Gravely E, Bernreuter M. The cost of shared governance. J Nurs Adm. 1994;24:44.
   PubMed Web of Science ®Google Scholar
• Mason JM, Lin DC, Wei X, et al. Functional characterization of CFI-400945, a Polo-like kinase 4 inhibitor, as a potential anticancer agent. Cancer Cell. 2014;26:163–176.
   PubMed Web of Science ®Google Scholar
• van de Vijver MJ, He YD, van’t Veer LJ, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002;347:1999–2009.
   PubMed Web of Science ®Google Scholar
• Cajanek L, Glatter T, Nigg EA. The E3 ubiquitin ligase Mib1 regulates Plk4 and centriole biogenesis. J Cell Sci. 2015;128:1674–1682.
   PubMed Web of Science ®Google Scholar
• Nakamura T, Saito H, Takekawa M. SAPK pathways and p53 cooperatively regulate PLK4 activity and centrosome integrity under stress. Nat Commun. 2013;4:1775.
   PubMed Web of Science ®Google Scholar
• Avruch J. MAP kinase pathways: the first twenty years. BiochimBiophysActa. 2007;1773:1150–1160.
   PubMed Web of Science ®Google Scholar
• Ventura JJ, Hubner A, Zhang C, et al. Chemical genetic analysis of the time course of signal transduction by JNK. Mol Cell. 2006;21:701–710.
   PubMed Web of Science ®Google Scholar
• Arimoto K, Fukuda H, Imajoh-Ohmi S, et al. Formation of stress granules inhibits apoptosis by suppressing stress-responsive MAPK pathways. Nat Cell Biol. 2008;10:1324–1332.
   PubMed Web of Science ®Google Scholar
• Brosh R, Rotter V. When mutants gain new powers: news from the mutant p53 field. Nat Rev Cancer. 2009;9:701–713.
   PubMed Web of Science ®Google Scholar
• Whitmarsh AJ, Davis RJ. Role of mitogen-activated protein kinase kinase 4 in cancer. Oncogene. 2007;26:3172–3184.
   PubMed Web of Science ®Google Scholar
• Fournier M, Tora L. KAT2-mediated PLK4 acetylation contributes to genomic stability by preserving centrosome number. Mol Cell Oncol. 2016;4:e1270391.
   PubMed Web of Science ®Google Scholar
• Li J, Tan M, Li L, et al. SAK, a new polo-like kinase, is transcriptionally repressed by p53 and induces apoptosis upon RNAi silencing. Neoplasia. 2005;7:312–323.
   PubMed Web of Science ®Google Scholar
• Farmer G, Friedlander P, Colgan J, et al. Transcriptional repression by p53 involves molecular interactions distinct from those with the TATA box binding protein. Nucleic Acids Res. 1996;24:4281–4288.
   PubMed Web of Science ®Google Scholar
• Wu Y, Mehew JW, Heckman CA, et al. Negative regulation of bcl-2 expression by p53 in hematopoietic cells. Oncogene. 2001;20:240–251.
   PubMed Web of Science ®Google Scholar
• Murphy M, Ahn J, Walker KK, et al. Transcriptional repression by wild-type p53 utilizes histone deacetylases, mediated by interaction with mSin3a. Genes Dev. 1999;132:2490–2501.
   Google Scholar
• Ward A, Hudson JW. p53-Dependent and cell specific epigenetic regulation of the polo-like kinases under oxidative stress. PLoS One. 2014;9:e87918.
   PubMed Web of Science ®Google Scholar
• Hervouet E, Vallette FM, Cartron PF. Dnmt3/transcription factor interactions as crucial players in targeted DNA methylation. Epigenetics. 2009;4:487–499.
   PubMed Web of Science ®Google Scholar
• Sercin O, Larsimont JC, Karambelas AE, et al. Transient PLK4 overexpression accelerates tumorigenesis in p53-deficient epidermis. Nat Cell Biol. 2016;18:100–110.
   PubMed Web of Science ®Google Scholar
• Vitre B, Holland AJ, Kulukian A, et al. Chronic centrosome amplification without tumorigenesis. Proc Natl Acad Sci U S A. 2015;112:E6321–E6330.
   PubMed Web of Science ®Google Scholar
• Silverman JS, Skaar JR, Pagano M. SCF ubiquitin ligases in the maintenance of genome stability. Trends Biochem Sci. 2012;37:66–73.
   PubMed Web of Science ®Google Scholar
• Zheng J, Yang X, Harrell JM, et al. CAND1 binds to unneddylated CUL1 and regulates the formation of SCF ubiquitin E3 ligase complex. Mol Cell. 2002;10:1519–1526.
   PubMed Web of Science ®Google Scholar
• Korzeniewski N, Hohenfellner M, Duensing S. CAND1 promotes PLK4-mediated centriole overduplication and is frequently disrupted in prostate cancer. Neoplasia. 2012;14:799–806.
   PubMed Web of Science ®Google Scholar
• Fan G, Sun L, Shan P, et al. Loss of KLF14 triggers centrosome amplification and tumorigenesis. Nat Commun. 2015;6:8450.
   PubMed Web of Science ®Google Scholar
• Stopa N, Krebs JE, Shechter D. The PRMT5 arginine methyltransferase: many roles in development, cancer and beyond. Cell Mol Life Sci. 2015;72:2041–2059.
   PubMed Web of Science ®Google Scholar
• Sivakumar G. “Polo-like kinase 4 at the nexus of epigenetic modifications and the DNA damage signaling network” (2014). Elect Theses Dissert. 5146.
   Google Scholar
• Jansson M, Durant ST, Cho EC, et al. Arginine methylation regulates the p53 response. Nat Cell Biol. 2008;10:1431–1439.
   PubMed Web of Science ®Google Scholar
• Xiao G, Chicas A, Olivier M, et al. A DNA damage signal is required for p53 to activate gadd45. Cancer Res. 2000;60:1711–1719.
   PubMed Web of Science ®Google Scholar
• Harkin DP, Bean JM, Miklos D, et al. Induction of GADD45 and JNK/SAPK-dependent apoptosis following inducible expression of BRCA1. Cell. 1999;97:575–586.
   PubMed Web of Science ®Google Scholar
• Holland AJ, Fachinetti D, Zhu Q, et al. The autoregulated instability of Polo-like kinase 4 limits centrosome duplication to once per cell cycle. Genes Dev. 2012;26:2684–2689.
   PubMed Web of Science ®Google Scholar
• Cunha-Ferreira I, Bento I, Pimenta-Marques A, et al. Regulation of autophosphorylation controls PLK4 self-destruction and centriole number. Curr Biol. 2013;23:2245–2254.
   PubMed Web of Science ®Google Scholar
• Zheng N, Schulman BA, Song L, et al. Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex. Nature. 2002;416:703–709.
   PubMed Web of Science ®Google Scholar
• Reinhardt HC, Yaffe MB. Phospho-Ser/Thr-binding domains: navigating the cell cycle and DNA damage response. Nat Rev Mol Cell Biol. 2013;14:563–580.
   PubMed Web of Science ®Google Scholar
• Strebhardt K. Multifaceted polo-like kinases: drug targets and antitargets for cancer therapy. Nat Rev Drug Discov. 2010;9:643–660.
   PubMed Web of Science ®Google Scholar
• Ko MA, Rosario CO, Hudson JW, et al. Plk4 haploinsufficiency causes mitotic infidelity and carcinogenesis. Nat Genet. 2005;37:883–888.
   PubMed Web of Science ®Google Scholar
• Li Z, Dai K, Wang C, et al. Expression of Polo-Like Kinase 4(PLK4) in breast cancer and its response to taxane-based neoadjuvant chemotherapy. J Cancer. 2016;7:1125–1132.
   PubMed Web of Science ®Google Scholar
• Kops GJ, Weaver BA, Cleveland DW. On the road to cancer: aneuploidy and the mitotic checkpoint. Nat Rev Cancer. 2005;5:773–785.
   PubMed Web of Science ®Google Scholar
• Levine MS, Bakker B, Boeckx B, et al. Centrosome amplification is sufficient to promote spontaneous tumorigenesis in mammals. Dev Cell. 2017;40:313–322.
   PubMed Web of Science ®Google Scholar
• Raff JW, Basto R. Centrosome amplification and cancer: a question of sufficiency. Dev Cell. 2017;40:217–218.
   PubMed Web of Science ®Google Scholar
• Mason J, Wei S, Luo X, et al. Inhibition of Polo-like kinase 4 as an anti-cancer strategy. [abstract]. In: proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR. Cancer Res. 2011;71(8Suppl):Abstract nr LB–215.
   Google Scholar
• Lee MY, Moreno CS, Saavedra HI. E2F activators signal and maintain centrosome amplification in breast cancer cells. Mol Cell Biol. 2014;34:2581–2599.
   PubMed Web of Science ®Google Scholar
• Fry AM. The Nek2 protein kinase: a novel regulator of centrosome structure. Oncogene. 2002;21:6184–6194.
   PubMed Web of Science ®Google Scholar
• Marina M, Saavedra HI. Nek2 and Plk4: prognostic markers, drivers of breast tumorigenesis and drug resistance. Front Biosci (Landmark Ed). 2014;19:352–365.
   PubMed Web of Science ®Google Scholar
• zurHausen H. Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer. 2002;2:342–350.
   PubMed Web of Science ®Google Scholar
• Korzeniewski N, Spardy N, Duensing A, et al. Genomic instability and cancer: lessons learned from human papillomaviruses. Cancer Lett. 2011;305:113–122.
   PubMed Web of Science ®Google Scholar
• Korzeniewski N, Treat B, Duensing S. The HPV-16 E7 oncoprotein induces centriole multiplication through deregulation of Polo-like kinase 4 expression. Mol Cancer. 2011;10:61.
   PubMed Web of Science ®Google Scholar
• Fischer M, Quaas M, Wintsche A, et al. Polo-like kinase 4 transcription is activated via CRE and NRF1 elements, repressed by DREAM through CDE/CHR sites and deregulated by HPV E7 protein. Nucleic Acids Res. 2014;42:163–180.
   PubMed Web of Science ®Google Scholar
• Johnson KA, Tan M, Sutterlin C. Centrosome abnormalities during a Chlamydia trachomatis infection are caused by dysregulation of the normal duplicationpathway. Cell Microbiol. 2009;11:1064–1073.
   PubMed Web of Science ®Google Scholar
• Kuriyama R, Bettencourt-Dias M, Hoffmann I, et al. Gamma-tubulin-containing abnormal centrioles are induced by insufficient Plk4 in human HCT116 colorectal cancer cells. J Cell Sci. 2009;122:2014–2023.
   PubMed Web of Science ®Google Scholar
• Swallow CJ, Ko MA, Siddiqui NU, et al. Sak/Plk4 and mitotic fidelity. Oncogene. 2005;24:306–312.
   PubMed Web of Science ®Google Scholar
• Pellegrino R, Calvisi DF, Ladu S, et al. Oncogenic and tumor suppressive roles of polo-like kinases in human hepatocellular carcinoma. Hepatology. 2010;51:857–868.
   PubMed Web of Science ®Google Scholar
• Holland AJ, Lan W, Cleveland DW. Centriole duplication: a lesson in self-control. Cell Cycle. 2010;9:2731–2736.
   PubMed Web of Science ®Google Scholar
• Ward A, Morettin A, Shum D, et al. Aberrant methylation of Polo-like kinase CpG islands in Plk4 heterozygous mice. BMC Cancer. 2011;11:71.
   PubMed Web of Science ®Google Scholar
• Liu L, Zhang CZ, Cai M, et al. Downregulation of polo-like kinase 4 in hepatocellular carcinoma associates with poor prognosis. PLoS One. 2012;7:e41293.
   PubMed Web of Science ®Google Scholar
• Ward A, Sivakumar G, Kanjeekal S, et al. The deregulated promoter methylation of the Polo-like kinases as a potential biomarker in hematological malignancies. Leuk Lymphoma. 2015;56:2123–2133.
   PubMed Web of Science ®Google Scholar
• Sredni ST, Tomita T. The polo-like kinase 4 gene (PLK4) is overexpressed in pediatric medulloblastoma. Childs Nerv Syst. 2017.
   PubMed Web of Science ®Google Scholar
• Sredni ST, Suzuki M, Yang JP, et al. A functional screening of the kinome identifies the Polo-like kinase 4 as a potential therapeutic target for malignant rhabdoid tumors, and possibly, other embryonal tumors of the brain. Pediatr Blood Cancer. 2017;64:e26551.
   Web of Science ®Google Scholar
• Marthiens V, Rujano MA, Pennetier C, et al. Centrosome amplification causes microcephaly. Nat Cell Biol. 2013;15:731–740.
   PubMed Web of Science ®Google Scholar
• Martin CA, Ahmad I, Klingseisen A, et al. Mutations in PLK4, encoding a master regulator of centriole biogenesis, cause microcephaly, growth failure and retinopathy. Nat Genet. 2014;46:1283–1292.
   PubMed Web of Science ®Google Scholar
• Shaheen R, Al Tala S, Almoisheer A, et al. Mutation in PLK4, encoding a master regulator of centriole formation, defines a novel locus for primordial dwarfism. J Med Genet. 2014;51:814–816.
   PubMed Web of Science ®Google Scholar
• McCoy RC, Demko Z, Ryan A, et al. Common variants spanning PLK4 are associated with mitotic-origin aneuploidy in human embryos. Science. 2015;348:235–238.
   PubMed Web of Science ®Google Scholar
• Zhang Q, Li G, Zhang L, et al. Maternal common variant rs2305957 spanning PLK4 is associated with blastocyst formation and early recurrent miscarriage. Fertil Steril. 2017;107:1034–1040.
   PubMed Web of Science ®Google Scholar
• Dominguez-Brauer C, Thu KL, Mason JM, et al. Targeting mitosis in cancer: emerging strategies. Mol Cell. 2015;60:524–536.
   PubMed Web of Science ®Google Scholar
• Chng WJ, Braggio E, Mulligan G, et al. The centrosome index is a powerful prognostic marker in myeloma and identifies a cohort of patients that might benefit from aurora kinase inhibition. Blood. 2008;111:1603–1609.
   PubMed Web of Science ®Google Scholar
• Hu Z, Fan C, Oh DS, et al. The molecular portraits of breast tumors are conserved across microarray platforms. BMC Genomics. 2006;7:96.
   PubMed Web of Science ®Google Scholar
• Laufer R, Forrest B, Li SW, et al. The discovery of PLK4 inhibitors: (E)-3-((1H-Indazol-6-yl)methylene)indolin-2-ones as novel antiproliferative agents. J Med Chem. 2013;56:6069–6087.
   PubMed Web of Science ®Google Scholar
• Holland AJ, Cleveland DW. Polo-like kinase 4 inhibition: a strategy for cancer therapy? Cancer Cell. 2014;26:151–153.
   PubMed Web of Science ®Google Scholar
• Sampson PB, Liu Y, Patel NK, et al. The discovery of Polo-like kinase 4 inhibitors: design and optimization of Spiro[cyclopropane-1,3’[3H]indol]-2’(1’H)-ones as orally bioavailable antitumor agents. J Med Chem. 2014;58:130–146.
   PubMed Web of Science ®Google Scholar
• Laufer R, Pauls HW, Feher M, et al. Kinase inhibitors and method of treating cancer with same. Wo. 2011;2011123937:A1.
   Google Scholar
• Lohse I, Mason J, Cao PM, et al. Activity of the novel polo-like kinase 4 inhibitor CFI-400945 in pancreatic cancer patient-derived xenografts. Oncotarget. 2017;8:3064–3071.
   PubMed Web of Science ®Google Scholar
• Sampson PB, Liu Y, Forrest B, et al. The discovery of Polo-like kinase 4 inhibitors: identification of (1R,2S).2-(3-((E).4-(((cis).2,6-dimethylmorpholino)methyl)styryl). 1H.indazol-6-yl)-5 ’-methoxyspiro[cyclopropane-1,3 ’indolin]-2 ’-one (CFI-400945) as a potent, orally active antitumor agent. J Med Chem. 2015;58:147–169.
   PubMed Web of Science ®Google Scholar
• Yu B, Yu Z, Qi PP, et al. Discovery of orally active anticancer candidate CFI-400945 derived from biologically promising spirooxindoles: success and challenges. Eur J Med Chem. 2015;95:35–40.
   PubMed Web of Science ®Google Scholar
• A study of CFI-400945 fumarate in patients with advanced cancer. 2013. [cited 2017 Apr 2014]. Available from: https://clinicaltrials.gov/ct2/show/NCT01954316
   Google Scholar
• A study of CFI-400945 fumarate in patients with relapsed or refractory acute myeloid leukemia or myelodysplastic syndrome. 2017. [cited 2017 jun 19]. Available from: https://clinicaltrials.gov/ct2/show/NCT03187288
   Google Scholar
• Wong YL, Anzola JV, Davis RL, et al. Cell biology. Reversible centriole depletion with an inhibitor of Polo-like kinase 4. Science. 2015;348:1155–1160.
   PubMed Web of Science ®Google Scholar
• Tovar C, Higgins B, Deo D, et al. Small-molecule inducer of cancer cell polyploidy promotes apoptosis or senescence: implications for therapy. Cell Cycle. 2010;9:3364–3375.
   PubMed Web of Science ®Google Scholar
• Morris EJ, Kawamura E, Gillespie JA, et al. Stat3 regulates centrosome clustering in cancer cells via Stathmin/PLK1. Nat Commun. 2017;8:15289.
   PubMed Web of Science ®Google Scholar
• Raab MS, Breitkreutz I, Anderhub S, et al. GF-15, a novel inhibitor of centrosomal clustering, suppresses tumor cell growth in vitro and in vivo. Cancer Res. 2012;72:5374–5385.
   PubMed Web of Science ®Google Scholar