PLK4

Summary

Gene Symbol: PLK4
Description: polo like kinase 4
Alias: MCCRP2, SAK, STK18, serine/threonine-protein kinase PLK4, Snk akin kinase, serine/threonine-protein kinase 18, serine/threonine-protein kinase Sak
Species: human
Products:     PLK4

Top Publications

  1. MacMillan J, Hudson J, Bull S, Dennis J, Swallow C. Comparative expression of the mitotic regulators SAK and PLK in colorectal cancer. Ann Surg Oncol. 2001;8:729-40 pubmed
    Disruption of normal mechanisms for cell cycle regulation is important in carcinogenesis. SAK and PLK are members of the polo family of serine threonine kinases, which in lower organisms have been shown to be required for the precise ..
  2. Cizmecioglu O, Arnold M, Bahtz R, Settele F, Ehret L, Haselmann Weiss U, et al. Cep152 acts as a scaffold for recruitment of Plk4 and CPAP to the centrosome. J Cell Biol. 2010;191:731-9 pubmed publisher
    Both gain and loss of function studies have identified the Polo-like kinase Plk4/Sak as a crucial regulator of centriole biogenesis, but the mechanisms governing centrosome duplication are incompletely understood...
  3. Martin C, Ahmad I, Klingseisen A, Hussain M, Bicknell L, Leitch 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 publisher
    ..Here we identify mutations in the genes encoding PLK4 kinase, a master regulator of centriole duplication, and its substrate TUBGCP6 in individuals with microcephalic ..
  4. Guderian G, Westendorf J, Uldschmid A, Nigg E. Plk4 trans-autophosphorylation regulates centriole number by controlling betaTrCP-mediated degradation. J Cell Sci. 2010;123:2163-9 pubmed publisher
    ..The centriolar protein Polo-like kinase 4 (Plk4) is a key regulator of centriole biogenesis and is crucial for maintaining constant centriole number, but the ..
  5. Rosario C, Ko M, Haffani Y, Gladdy R, Paderova J, Pollett A, et al. Plk4 is required for cytokinesis and maintenance of chromosomal stability. Proc Natl Acad Sci U S A. 2010;107:6888-93 pubmed publisher
    ..The polo family kinase Plk4/Sak is required for late mitotic progression and is haploinsufficient for tumor suppression in mice...
  6. Yamashita Y, Kajigaya S, Yoshida K, Ueno S, Ota J, Ohmine K, et al. Sak serine-threonine kinase acts as an effector of Tec tyrosine kinase. J Biol Chem. 2001;276:39012-20 pubmed
    The murine sak gene encodes a putative serine-threonine kinase which is homologous to the members of the Plk/Polo family...
  7. Kim T, Park J, Shukla A, Choi S, Murugan R, Lee J, et al. Hierarchical recruitment of Plk4 and regulation of centriole biogenesis by two centrosomal scaffolds, Cep192 and Cep152. Proc Natl Acad Sci U S A. 2013;110:E4849-57 pubmed publisher
    ..Although it is well appreciated that polo-like kinase 4 (Plk4) plays a central role in centriole biogenesis, how it is recruited to centrosomes and whether this step is ..
  8. Bonni S, Ganuelas M, Petrinac S, Hudson J. Human Plk4 phosphorylates Cdc25C. Cell Cycle. 2008;7:545-7 pubmed
  9. Kleylein Sohn J, Westendorf J, Le Clech M, Habedanck R, Stierhof Y, Nigg E. Plk4-induced centriole biogenesis in human cells. Dev Cell. 2007;13:190-202 pubmed
    We show that overexpression of Polo-like kinase 4 (Plk4) in human cells induces centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole...

More Information

Publications97

  1. Habedanck R, Stierhof Y, Wilkinson C, Nigg E. The Polo kinase Plk4 functions in centriole duplication. Nat Cell Biol. 2005;7:1140-6 pubmed
    ..By contrast, the functions of other mammalian Polo family members remain largely unknown. Plk4 is the most structurally divergent Polo family member; it is maximally expressed in actively dividing tissues and ..
  2. Liu L, Zhang C, Cai M, Fu J, Chen G, Yun J. Downregulation of polo-like kinase 4 in hepatocellular carcinoma associates with poor prognosis. PLoS ONE. 2012;7:e41293 pubmed publisher
    Polo-like kinase 4 (PLK4), belonging to serine/threonine kinase family, is critical for centriole replication and cell cycle progression. PLK4 has been proposed as a tumor suppressor in hepatocellular carcinoma (HCC)...
  3. Vulprecht J, David A, Tibelius A, Castiel A, Konotop G, Liu F, et al. STIL is required for centriole duplication in human cells. J Cell Sci. 2012;125:1353-62 pubmed publisher
    Centrioles are key structural elements of centrosomes and primary cilia. In mammals, only a few proteins including PLK4, CPAP (CENPJ), SAS6, CEP192, CEP152 and CEP135 have thus far been identified to be required for centriole duplication...
  4. 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 publisher
    ..Thus, our results reveal a mechanism that preserves the numeral integrity of centrosomes, and an unexplored tumour-suppressive function of MKK4...
  5. Hatch E, Kulukian A, Holland A, Cleveland D, Stearns T. Cep152 interacts with Plk4 and is required for centriole duplication. J Cell Biol. 2010;191:721-9 pubmed publisher
    ..Centrioles duplicate once per cell cycle, and duplication requires Plk4, a member of the Polo-like kinase family; however, the mechanism linking Plk4 activity and centriole formation is ..
  6. Korzeniewski N, Zheng L, Cuevas R, Parry J, Chatterjee P, Anderton B, et al. Cullin 1 functions as a centrosomal suppressor of centriole multiplication by regulating polo-like kinase 4 protein levels. Cancer Res. 2009;69:6668-75 pubmed publisher
    ..We found that this activity of CUL1 involves the degradation of Polo-like kinase 4 (PLK4) at maternal centrioles...
  7. Puklowski A, Homsi Y, Keller D, May M, Chauhan S, Kossatz U, et al. The SCF-FBXW5 E3-ubiquitin ligase is regulated by PLK4 and targets HsSAS-6 to control centrosome duplication. Nat Cell Biol. 2011;13:1004-9 pubmed publisher
    ..The activity of SCF-FBXW5 is in turn negatively regulated by Polo-like kinase 4 (PLK4), which phosphorylates FBXW5 at Ser 151 to suppress its ability to ubiquitylate HsSAS-6...
  8. Tang C, Lin S, Hsu W, Lin Y, Wu C, Lin Y, et al. The human microcephaly protein STIL interacts with CPAP and is required for procentriole formation. EMBO J. 2011;30:4790-804 pubmed publisher
    ..STIL depletion inhibited normal centriole duplication, Plk4-induced centriole amplification, and CPAP-induced centriole elongation, and resulted in a failure to localize hSAS6 ..
  9. Sillibourne J, Tack F, Vloemans N, Boeckx A, Thambirajah S, Bonnet P, et al. Autophosphorylation of polo-like kinase 4 and its role in centriole duplication. Mol Biol Cell. 2010;21:547-61 pubmed publisher
    Centrosome duplication occurs once every cell cycle in a strictly controlled manner. Polo-like kinase 4 (PLK4) is a key regulator of this process whose kinase activity is essential for centriole duplication...
  10. Dzhindzhev N, Yu Q, Weiskopf K, Tzolovsky G, Cunha Ferreira I, Riparbelli M, et al. Asterless is a scaffold for the onset of centriole assembly. Nature. 2010;467:714-8 pubmed publisher
    ..Centriole assembly and duplication is controlled by Polo-like-kinase 4 (Plk4): these processes fail if Plk4 is downregulated and are promoted by Plk4 overexpression...
  11. Arquint C, Sonnen K, Stierhof Y, Nigg E. Cell-cycle-regulated expression of STIL controls centriole number in human cells. J Cell Sci. 2012;125:1342-52 pubmed publisher
    ..each mother, which is highly reminiscent of the phenotype produced by overexpression of the polo-like kinase PLK4 or the spindle assembly abnormal protein 6 homolog (SAS-6)...
  12. Sonnen K, Gabryjonczyk A, Anselm E, Stierhof Y, Nigg E. Human Cep192 and Cep152 cooperate in Plk4 recruitment and centriole duplication. J Cell Sci. 2013;126:3223-33 pubmed publisher
    Polo-like kinase 4 (Plk4) is a key regulator of centriole duplication, but the mechanism underlying its recruitment to mammalian centrioles is not understood...
  13. Li J, Tan M, Li L, Pamarthy D, Lawrence T, Sun Y. SAK, a new polo-like kinase, is transcriptionally repressed by p53 and induces apoptosis upon RNAi silencing. Neoplasia. 2005;7:312-23 pubmed
    Chip profiling of a p53 temperature-sensitive tumor model identified SAK (Snk/Plk-akin kinase), encoding a new member of polo-like kinases (PLKs), as a gene strongly repressed by wild-type p53...
  14. Bettencourt Dias M, Rodrigues Martins A, Carpenter L, Riparbelli M, Lehmann L, Gatt M, et al. SAK/PLK4 is required for centriole duplication and flagella development. Curr Biol. 2005;15:2199-207 pubmed
    SAK/PLK4 is a distinct member of the polo-like kinase family. SAK-/- mice die during embryogenesis, whereas SAK+/- mice develop liver and lung tumors and SAK+/- MEFs show mitotic abnormalities...
  15. Miller J, Liu Y, Williams C, Smith H, O Connell K. The E2F-DP1 Transcription Factor Complex Regulates Centriole Duplication in Caenorhabditis elegans. G3 (Bethesda). 2016;6:709-20 pubmed publisher
    ..Recent studies have revealed that posttranslational control of the master regulator Plk4/ZYG-1 kinase and its downstream effector SAS-6 is key to ensuring production of a single daughter centriole...
  16. Flanagan A, Stavenschi E, Basavaraju S, Gaboriau D, Hoey D, Morrison C. Centriole splitting caused by loss of the centrosomal linker protein C-NAP1 reduces centriolar satellite density and impedes centrosome amplification. Mol Biol Cell. 2017;28:736-745 pubmed publisher
    ..Centrosome amplification induced by DNA damage or by PLK4 or CDK2 overexpression was markedly reduced in the absence of C-NAP1...
  17. Bauer M, Cubizolles F, Schmidt A, Nigg E. Quantitative analysis of human centrosome architecture by targeted proteomics and fluorescence imaging. EMBO J. 2016;35:2152-2166 pubmed
    ..conserved mechanisms underlying centrosome biogenesis are centered on a set of key proteins, including Plk4, Sas-6, and STIL, whose exact levels are critical to ensure accurate reproduction of centrioles during cell cycle ..
  18. Wolf B, Balestra F, Spahr A, Gönczy P. ZYG-1 promotes limited centriole amplification in the C. elegans seam lineage. Dev Biol. 2018;434:221-230 pubmed publisher
    ..We found that overexpression of the Plk4-related kinase ZYG-1 leads to the formation of one supernumerary centriolar focus per parental centriole during the ..
  19. Baek I, Jang Y, Lee T, Lee J. Kinetic analysis of de novo centriole assembly in heat-shocked mammalian cells. Cytoskeleton (Hoboken). 2017;74:18-28 pubmed publisher
    ..Plk) 4 expression, and the formation of a complex containing ?-tubulin, pericentrin, HS protein (Hsp) 90, and Plk4, in approximately half of the cells...
  20. Khokhlova O, Hung W, Wan T, Iwao Y, Takano T, Higuchi W, et al. Healthcare- and Community-Associated Methicillin-Resistant Staphylococcus aureus (MRSA) and Fatal Pneumonia with Pediatric Deaths in Krasnoyarsk, Siberian Russia: Unique MRSA's Multiple Virulence Factors, Genome, and Stepwise Evolution. PLoS ONE. 2015;10:e0128017 pubmed publisher
    ..PSMα/Hld expression, α-hemolysin, the staphylococcal enterotoxin SEK/SEQ, the immune evasion factor SCIN/SAK, and collagen adhesin. Regarding ST8Kras, SEA was included in MVFs, some of which were common to ST239Kras...
  21. Hoh R, Stowe T, Turk E, Stearns T. Transcriptional program of ciliated epithelial cells reveals new cilium and centrosome components and links to human disease. PLoS ONE. 2012;7:e52166 pubmed publisher
    ..Most, but not all, of known centrosome proteins are transcriptionally upregulated early, particularly Plk4, a master regulator of centriole formation...
  22. Gottardo M, Callaini G, Riparbelli M. Klp10A modulates the localization of centriole-associated proteins during Drosophila male gametogenesis. Cell Cycle. 2016;15:3432-3441 pubmed publisher
    ..In the absence of Klp10A the distribution of Drosophila pericentrin-like protein (Dplp), Sas-4 and Sak/Plk4 that are restricted in control testes to the proximal end of the centriole increase along the centriole length...
  23. Peel N, Iyer J, Naik A, Dougherty M, Decker M, O Connell K. Protein Phosphatase 1 Down Regulates ZYG-1 Levels to Limit Centriole Duplication. PLoS Genet. 2017;13:e1006543 pubmed publisher
    ..The C. elegans homolog of Plk4, ZYG-1, is required for centriole duplication, but our understanding of how ZYG-1 levels are regulated remains ..
  24. Fu J, Lipinszki Z, Rangone H, Min M, Mykura C, Chao Chu J, et al. Conserved molecular interactions in centriole-to-centrosome conversion. Nat Cell Biol. 2016;18:87-99 pubmed publisher
    ..is essential for loading Asterless or Cep152, the partner of the master regulator of centriole duplication, Plk4. Our study thus uncovers the molecular basis for centriole-to-centrosome conversion that renders daughter ..
  25. Egyir B, Guardabassi L, Monecke S, Addo K, Newman M, Larsen A. Methicillin-resistant Staphylococcus aureus strains from Ghana include USA300. J Glob Antimicrob Resist. 2015;3:26-30 pubmed publisher
    ..All MRSA contained sak and scn genes, one isolate (ST36-II) harboured the gene encoding the toxic shock syndrome toxin (TSST) and none ..
  26. Vandendriessche S, de Boeck H, Deplano A, Phoba M, Lunguya O, Falay D, et al. Characterisation of Staphylococcus aureus isolates from bloodstream infections, Democratic Republic of the Congo. Eur J Clin Microbiol Infect Dis. 2017;36:1163-1171 pubmed publisher
    ..TSST-1 was associated with CC8-spa t1476-SCCmec V. The immune evasion cluster (IEC) genes scn, sak and chp were detected in 81.5% of isolates (88/108, equally represented among MSSA and MRSA)...
  27. Feltrin F, Alba P, Kraushaar B, Ianzano A, Argudín M, Di Matteo P, et al. A Livestock-Associated, Multidrug-Resistant, Methicillin-Resistant Staphylococcus aureus Clonal Complex 97 Lineage Spreading in Dairy Cattle and Pigs in Italy. Appl Environ Microbiol. 2016;82:816-21 pubmed publisher
    ..All CC97 isolates were Panton-Valentine leukocidin (PVL) negative, and a few (n = 7) tested positive for sak or scn...
  28. Jebamercy G, Prithika U, Lavanya N, Sekar C, Balamurugan K. Changes in Caenorhabditis elegans immunity and Staphylococcal virulence factors during their interactions. Gene. 2015;558:159-72 pubmed publisher
    ..The qPCR analyses indicated the upregulation of ltaS and other virulence genes (atoxin, sak, ssaA and fbe) during infection...
  29. Khemiri M, Akrout Alhusain A, Abbassi M, El Ghaieb H, Santos Costa S, Belas A, et al. Clonal spread of methicillin-resistant Staphylococcus aureus-t6065-CC5-SCCmecV-agrII in a Libyan hospital. J Glob Antimicrob Resist. 2017;10:101-105 pubmed publisher
    ..sec: 26, sea: 6, sek: 5), haemolysin (hla (32), hld (32), hlg (32)) and immune evasion cluster proteins (scn: 32, sak: 32) were relevant...
  30. Galletta B, Fagerstrom C, Schoborg T, McLamarrah T, Ryniawec J, Buster D, et al. A centrosome interactome provides insight into organelle assembly and reveals a non-duplication role for Plk4. Nat Commun. 2016;7:12476 pubmed publisher
    ..Finally, we identified a novel role for Plk4, the master regulator of centriole duplication...
  31. Pagan J, Marzio A, Jones M, Saraf A, Jallepalli P, Florens L, et al. Degradation of Cep68 and PCNT cleavage mediate Cep215 removal from the PCM to allow centriole separation, disengagement and licensing. Nat Cell Biol. 2015;17:31-43 pubmed publisher
  32. Bury L, Coelho P, Simeone A, Ferries S, Eyers C, Eyers P, et al. Plk4 and Aurora A cooperate in the initiation of acentriolar spindle assembly in mammalian oocytes. J Cell Biol. 2017;216:3571-3590 pubmed publisher
    ..We now demonstrate that partially overlapping, nonredundant functions of Aurora A and Plk4 kinases contribute to initiate acentriolar meiosis I spindle formation...
  33. Morris Rosendahl D, Kaindl A. What next-generation sequencing (NGS) technology has enabled us to learn about primary autosomal recessive microcephaly (MCPH). Mol Cell Probes. 2015;29:271-81 pubmed publisher
    ..The functions of proteins such as WDR62, CASC5, PHC1, CDK6, CENP-E, CENP-F, CEP63, ZNF335, PLK4 and TUBGPC, have been added to the complex network of critical cellular processes known to be involved in brain ..
  34. Xu Y, Shi Y, Zhou J, Yang W, Bai L, Wang S, et al. Structure-based antigenic epitope and PEGylation improve the efficacy of staphylokinase. Microb Cell Fact. 2017;16:197 pubmed publisher
    Staphylokinase (Sak) holds promise for use in thrombolytic therapy for acute myocardial infarction. However, its immunogenicity is a major disadvantage under clinical conditions...
  35. Vitre B, Holland A, Kulukian A, Shoshani O, Hirai M, Wang Y, et al. Chronic centrosome amplification without tumorigenesis. Proc Natl Acad Sci U S A. 2015;112:E6321-30 pubmed publisher
    ..centrosome amplification can be induced by a Cre-recombinase-mediated increase in expression of Polo-like kinase 4 (Plk4)...
  36. Dominguez Brauer C, Thu K, Mason J, Blaser H, Bray M, Mak T. Targeting Mitosis in Cancer: Emerging Strategies. Mol Cell. 2015;60:524-36 pubmed publisher
    ..This reasoning stimulated our development of novel inhibitors targeting the critical regulators of genomic stability and the mitotic checkpoint: AURKA, PLK4, and Mps1/TTK.
  37. Guizzunti G, Seemann J. Mitotic Golgi disassembly is required for bipolar spindle formation and mitotic progression. Proc Natl Acad Sci U S A. 2016;113:E6590-E6599 pubmed
    ..These results demonstrate that Golgi disassembly is required for mitotic progression because failure to vesiculate the Golgi activates the canonical SAC. This requirement suggests that cells actively monitor Golgi integrity in mitosis. ..
  38. Serçin Ã, Larsimont J, Karambelas A, Marthiens V, Moers V, Boeckx B, et al. Transient PLK4 overexpression accelerates tumorigenesis in p53-deficient epidermis. Nat Cell Biol. 2016;18:100-10 pubmed publisher
    ..Using Plk4 overexpression (PLK4OE) during epidermal development, we assess the impact of centrosome amplification and ..
  39. Atici Y, Balioğlu M, Kargin D, Mert M, Albayrak A, Kaygusuz M. Analysis of complications following posterior vertebral column resection for the treatment of severe angular kyphosis greater than 100°. Acta Orthop Traumatol Turc. 2017;51:201-208 pubmed publisher
    ..the complications, efficacy and safety of posterior vertebral column resection (PVCR) in severe angular kyphosis (SAK) greater than 100°. The medical records of 17 patients (mean age 17...
  40. Alba P, Feltrin F, Cordaro G, Porrero M, Kraushaar B, Argudín M, et al. Livestock-Associated Methicillin Resistant and Methicillin Susceptible Staphylococcus aureus Sequence Type (CC)1 in European Farmed Animals: High Genetic Relatedness of Isolates from Italian Cattle Herds and Humans. PLoS ONE. 2015;10:e0137143 pubmed publisher
    ..genetic features typical of human adaptation or present in human-associated CC1: Immune evasion cluster (IEC) genes sak and scn, or sea; sat and aphA3-mediated aminoglycoside resistance...
  41. Kawakami M, Mustachio L, Zheng L, Chen Y, Rodriguez Canales J, Mino B, et al. Polo-like kinase 4 inhibition produces polyploidy and apoptotic death of lung cancers. Proc Natl Acad Sci U S A. 2018;115:1913-1918 pubmed publisher
    Polo-like kinase 4 (PLK4) is a serine/threonine kinase regulating centriole duplication. CFI-400945 is a highly selective PLK4 inhibitor that deregulates centriole duplication, causing mitotic defects and death of aneuploid cancers...
  42. Dinçer T, Yorgancıoğlu Budak G, Olmez A, Er İ, Dodurga Y, Özdemir Ö, et al. Analysis of centrosome and DNA damage response in PLK4 associated Seckel syndrome. Eur J Hum Genet. 2017;25:1118-1125 pubmed publisher
    ..1-q28.3 in a Turkish family. Direct sequencing of PLK4 (polo-like kinase 4) revealed a homozygous splicing acceptor site transition (c...
  43. Zitouni S, Francia M, Leal F, Montenegro Gouveia S, Nabais C, Duarte P, et al. CDK1 Prevents Unscheduled PLK4-STIL Complex Assembly in Centriole Biogenesis. Curr Biol. 2016;26:1127-37 pubmed publisher
    ..overcome this distance in early mitosis, at a time when triggers for centriole biogenesis Polo-like kinase 4 (PLK4) and its substrate STIL are abundant...
  44. Lopes C, Jana S, Cunha Ferreira I, Zitouni S, Bento I, Duarte P, et al. PLK4 trans-Autoactivation Controls Centriole Biogenesis in Space. Dev Cell. 2015;35:222-35 pubmed publisher
    ..Here, we show that trans-autoactivation of Polo-like kinase 4 (PLK4), the trigger of centriole biogenesis, is a critical event in the spatial control of that process...
  45. Sredni S, Suzuki M, Yang J, Topczewski J, Bailey A, Gokirmak T, 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: pubmed publisher
    ..The Polo-like kinase 4 (PLK4) was identified as the kinase that resulted in higher impairment of cell proliferation when mutated by CRISPR/Cas9...
  46. Arquint C, Nigg E. The PLK4-STIL-SAS-6 module at the core of centriole duplication. Biochem Soc Trans. 2016;44:1253-1263 pubmed
    ..In recent years, a module comprising the protein kinase polo-like kinase 4 (PLK4) and the two proteins STIL and SAS-6 have been shown to stay at the core of centriole duplication...
  47. Shrestha A, Hamilton G, O Neill E, Knapp S, Elkins J. Analysis of conditions affecting auto-phosphorylation of human kinases during expression in bacteria. Protein Expr Purif. 2012;81:136-143 pubmed publisher
    ..Remarkably, the Ser/Thr kinase PLK4 auto-phosphorylated on a tyrosine residue (Tyr177) located in the activation segment...
  48. Lambrus B, Uetake Y, Clutario K, Daggubati V, Snyder M, Sluder G, et al. p53 protects against genome instability following centriole duplication failure. J Cell Biol. 2015;210:63-77 pubmed publisher
    ..an auxin-inducible degradation system to achieve rapid, titratable, and reversible control of Polo-like kinase 4 (Plk4), a master regulator of centriole biogenesis...
  49. McCoy R, Demko Z, Ryan A, Banjevic M, Hill M, Sigurjonsson S, et al. Common variants spanning PLK4 are associated with mitotic-origin aneuploidy in human embryos. Science. 2015;348:235-8 pubmed publisher
    ..This associated region contains a candidate gene, Polo-like kinase 4 (PLK4), that plays a well-characterized role in centriole duplication and has the ability to alter mitotic fidelity upon ..
  50. Khire A, Vizuet A, Davila E, Avidor Reiss T. Asterless Reduction during Spermiogenesis Is Regulated by Plk4 and Is Essential for Zygote Development in Drosophila. Curr Biol. 2015;25:2956-63 pubmed publisher
    ..Asl reduction is regulated through a subset of its domains by the master regulator of centriole duplication Plk4 and by the ubiquitin ligase that targets Plk4 for degradation: Slimb...
  51. Pattanshetty S, Kotrashetti V, Nayak R, Bhat K, Somannavar P, Babji D. PCR based detection of HPV 16 and 18 genotypes in normal oral mucosa of tobacco users and non-users. Biotech Histochem. 2014;89:433-9 pubmed publisher
    ..We propose that HPVs16 and 18 commonly are present in normal oral mucosa and emphasize the importance of distinguishing clinical, subclinical and latent HPV infections when investigating HPVs and OSCC. ..
  52. Sampson P, Liu Y, Patel N, Feher M, Forrest B, Li S, 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. 2015;58:130-46 pubmed publisher
    Polo-like kinase 4 (PLK4), a unique member of the polo-like kinase family of serine-threonine kinases, is a master regulator of centriole duplication that is important for maintaining genome integrity...
  53. Ferguson F, Doctor Z, Chaikuad A, Sim T, Kim N, Knapp S, et al. Characterization of a highly selective inhibitor of the Aurora kinases. Bioorg Med Chem Lett. 2017;27:4405-4408 pubmed publisher
    ..selective inhibitor of Aurora kinases A, B and C, with potent cellular activity and minimal off-target activity (PLK4)...
  54. Maniswami R, Prashanth S, Karanth A, Koushik S, Govindaraj H, Mullangi R, et al. PLK4: A link between centriole biogenesis and cancer. Expert Opin Ther Targets. 2017;: pubmed publisher
    ..Polo like kinase-4 (PLK4) is one such kinase that appears in low abundance and plays a well-characterized role in centriole duplication...
  55. Cizmecioglu O, Warnke S, Arnold M, Duensing S, Hoffmann I. Plk2 regulated centriole duplication is dependent on its localization to the centrioles and a functional polo-box domain. Cell Cycle. 2008;7:3548-55 pubmed
    ..Furthermore, our results imply that Plk2 mediated centriole duplication is dependent on Plk4 function...
  56. Pohl M, von Recum Knepper J, Rodriguez Frandsen A, Lanz C, Yángüez E, Soonthornvacharin S, et al. Identification of Polo-like kinases as potential novel drug targets for influenza A virus. Sci Rep. 2017;7:8629 pubmed publisher
    ..We show that knockdown of PLK1, PLK3, and PLK4, as well as inhibition of PLK kinase activity by four different compounds, leads to reduced influenza virus ..
  57. Narváez A, Ber S, Crooks A, Emery A, Hardwick B, Guarino Almeida E, et al. Modulating Protein-Protein Interactions of the Mitotic Polo-like Kinases to Target Mutant KRAS. Cell Chem Biol. 2017;24:1017-1028.e7 pubmed publisher
    ..Poloppin kills cells expressing mutant KRAS, selectively enhancing death in mitosis. PLK1 or PLK4 depletion recapitulates these cellular effects, as does PBD overexpression, corroborating Poloppin's mechanism of ..
  58. Marina M, Saavedra H. Nek2 and Plk4: prognostic markers, drivers of breast tumorigenesis and drug resistance. Front Biosci (Landmark Ed). 2014;19:352-65 pubmed
    The Nek2 and Plk4 kinases serve as crucial regulators of mitotic processes such as the centrosome duplication cycle and spindle assembly...
  59. Fournier M, Orpinell M, Grauffel C, Scheer E, Garnier J, Ye T, et al. KAT2A/KAT2B-targeted acetylome reveals a role for PLK4 acetylation in preventing centrosome amplification. Nat Commun. 2016;7:13227 pubmed publisher
    ..One of the newly identified KAT2A/2B substrate is polo-like kinase 4 (PLK4), a key regulator of centrosome duplication...
  60. Niu N, Qin Y, Fridley B, Hou J, Kalari K, Zhu M, et al. Radiation pharmacogenomics: a genome-wide association approach to identify radiation response biomarkers using human lymphoblastoid cell lines. Genome Res. 2010;20:1482-92 pubmed publisher
    ..Functional validation using siRNA knockdown in multiple tumor cell lines showed that C13orf34, MAD2L1, PLK4, TPD52, and DEPDC1B each significantly altered radiation sensitivity in at least two cancer cell lines...
  61. Ledoux A, Sellier H, Gillies K, Iannetti A, James J, Perkins N. NF?B regulates expression of Polo-like kinase 4. Cell Cycle. 2013;12:3052-62 pubmed publisher
    ..that NF?B regulates the expression of genes required for centrosome duplication, and that Polo-like kinase 4 (PLK4) is a direct NF?B target gene...
  62. Kazazian K, Go C, Wu H, Brashavitskaya O, Xu R, Dennis J, et al. Plk4 Promotes Cancer Invasion and Metastasis through Arp2/3 Complex Regulation of the Actin Cytoskeleton. Cancer Res. 2017;77:434-447 pubmed publisher
    The polo family serine threonine kinase Plk4 has been proposed as a therapeutic target in advanced cancers based on increased expression in primary human cancers, facilitation of tumor growth in murine xenograft models, and centrosomal ..
  63. Arquint C, Gabryjonczyk A, Imseng S, Böhm R, Sauer E, Hiller S, et al. STIL binding to Polo-box 3 of PLK4 regulates centriole duplication. elife. 2015;4: pubmed publisher
    Polo-like kinases (PLK) are eukaryotic regulators of cell cycle progression, mitosis and cytokinesis; PLK4 is a master regulator of centriole duplication...
  64. Tsutsumi M, Yokoi S, Miya F, Miyata M, Kato M, Okamoto N, et al. Novel compound heterozygous variants in PLK4 identified in a patient with autosomal recessive microcephaly and chorioretinopathy. Eur J Hum Genet. 2016;24:1702-1706 pubmed publisher
    ..Polo-like kinase 4 (PLK4) is one of the centrosomal proteins required for centriole duplication...
  65. Sampson P, Liu Y, Forrest B, Cumming G, Li S, Patel N, 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 antitum. J Med Chem. 2015;58:147-69 pubmed
    Previous publications from our laboratory have introduced novel inhibitors of Polo-like kinase 4 (PLK4), a mitotic kinase identified as a potential target for cancer therapy...
  66. Shaheen R, Al Tala S, Almoisheer A, Alkuraya F. Mutation in PLK4, encoding a master regulator of centriole formation, defines a novel locus for primordial dwarfism. J Med Genet. 2014;51:814-6 pubmed publisher
    ..2, in which we identified a five base-pair deletion in PLK4, which encodes a master regulator of centriole duplication...
  67. Ward A, Hudson J. p53-Dependent and cell specific epigenetic regulation of the polo-like kinases under oxidative stress. PLoS ONE. 2014;9:e87918 pubmed publisher
    ..murine embryonic fibroblasts exposed to hypoxia and ROS displayed significant hypermethylation of Plk1 and Plk4 promoter regions post treatment. Corresponding proteins were also depleted by 40% after treatment...
  68. Holland A, Fachinetti D, Da Cruz S, Zhu Q, Vitre B, Lince Faria M, et al. Polo-like kinase 4 controls centriole duplication but does not directly regulate cytokinesis. Mol Biol Cell. 2012;23:1838-45 pubmed publisher
    ..Centrioles duplicate once per cell cycle, and duplication is coordinated by Polo-like kinase 4 (Plk4). We previously demonstrated that Plk4 accumulation is autoregulated by its own kinase activity...
  69. Neamah M, Mir Sanchis I, López Sanz M, Acosta S, Baquedano I, Haag A, et al. Sak and Sak4 recombinases are required for bacteriophage replication in Staphylococcus aureus. Nucleic Acids Res. 2017;45:6507-6519 pubmed publisher
    ..Here, analysing Sak and Sak4 as representatives of two different families of SSAPs present in phages infecting the clinically relevant ..
  70. Franck N, Montembault E, Romé P, Pascal A, Cremet J, Giet R. CDK11(p58) is required for centriole duplication and Plk4 recruitment to mitotic centrosomes. PLoS ONE. 2011;6:e14600 pubmed publisher
    ..Indeed, Plk4 protein kinase and the centrosomal protein Cep192, which are key components of the centriole duplication machinery, ..
  71. Hori A, Barnouin K, Snijders A, Toda T. A non-canonical function of Plk4 in centriolar satellite integrity and ciliogenesis through PCM1 phosphorylation. EMBO Rep. 2016;17:326-37 pubmed publisher
    Centrioles are the major constituents of the animal centrosome, in which Plk4 kinase serves as a master regulator of the duplication cycle. Many eukaryotes also contain numerous peripheral particles known as centriolar satellites...
  72. 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
    ..CAND1 was found to synergize with Polo-like kinase 4 (PLK4), a master regulator of centriole biogenesis, in the induction of centriole overduplication...
  73. Ling H, Hanashiro K, Luong T, Benavides L, Fukasawa K. Functional relationship among PLK2, PLK4 and ROCK2 to induce centrosome amplification. Cell Cycle. 2015;14:544-53 pubmed publisher
    ..in the cell cycle-arrested cells, including Rho-associated kinase (ROCK2), Polo-like kinase 2 (PLK2) and PLK4. Here, we tested whether these kinases induce centrosome amplification in a linear pathway or parallel pathways...
  74. Shinmura K, Kurabe N, Goto M, Yamada H, Natsume H, Konno H, et al. PLK4 overexpression and its effect on centrosome regulation and chromosome stability in human gastric cancer. Mol Biol Rep. 2014;41:6635-44 pubmed publisher
    Polo-like kinase 4 (PLK4) is a centrosomal protein that is involved in the regulation of centrosome duplication. This study aimed to determine whether the genetic abnormality of PLK4 is involved in human gastric cancer...
  75. Miyamoto T, Bando Y, Koh E, Tsujimura A, Miyagawa Y, Iijima M, et al. A PLK4 mutation causing azoospermia in a man with Sertoli cell-only syndrome. Andrology. 2016;4:75-81 pubmed publisher
    ..Male mice with a point mutation in the Plk4 gene show azoospermia associated with germ cell loss...
  76. Čajánek L, Glatter T, Nigg E. The E3 ubiquitin ligase Mib1 regulates Plk4 and centriole biogenesis. J Cell Sci. 2015;128:1674-82 pubmed publisher
    ..In mammalian cells, the centriole duplication cycle is governed by Polo-like kinase 4 (Plk4). Here, we identify the E3 ubiquitin ligase Mind bomb (Mib1) as a new interaction partner of Plk4...
  77. Arif M, Riaz M, Shahzad S, Yasmeen T, Ashraf M, Siddique M, et al. Fresh and composted industrial sludge restore soil functions in surface soil of degraded agricultural land. Sci Total Environ. 2018;619-620:517-527 pubmed publisher
    ..organic carbon (TOC), soil available nitrogen (SAN), soil available phosphorus (SAP) and soil available potassium (SAK) at 0-15cm depth. Soil enzyme activities i.e...
  78. Hudson J, Chen L, Fode C, Binkert C, Dennis J. Sak kinase gene structure and transcriptional regulation. Gene. 2000;241:65-73 pubmed
    ..Human Sak-a (Stk18) cDNA is reported to contain an insertion of sequence corresponding to the mouse Sak-b tail...
  79. Decher N, Kiper A, Rinné S. Stretch-activated potassium currents in the heart: Focus on TREK-1 and arrhythmias. Prog Biophys Mol Biol. 2017;130:223-232 pubmed publisher
    This review focuses on the role and the molecular candidates of the cardiac stretch-activated potassium current (SAK)...
  80. Park S, Park J, Kim T, Kim J, Kwak M, Ku B, et al. Molecular basis for unidirectional scaffold switching of human Plk4 in centriole biogenesis. Nat Struct Mol Biol. 2014;21:696-703 pubmed publisher
    Polo-like kinase 4 (Plk4) is a key regulator of centriole duplication, an event critical for the maintenance of genomic integrity...
  81. Lee M, Moreno C, Saavedra H. E2F activators signal and maintain centrosome amplification in breast cancer cells. Mol Cell Biol. 2014;34:2581-99 pubmed
    ..Our results revealed that E2Fs affect the expression of proteins, including Nek2 and Plk4, known to influence the cell/centrosome cycles and mitosis...
  82. Ward A, Sivakumar G, Kanjeekal S, Hamm C, Labute B, Shum D, et al. The deregulated promoter methylation of the Polo-like kinases as a potential biomarker in hematological malignancies. Leuk Lymphoma. 2015;56:2123-33 pubmed publisher
    ..than 70% of lymphoma and myelodysplastic syndrome (MDS)/leukemia bone marrow extracts display a hypermethylated PLK4 promoter region in comparison to the normal...
  83. 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 publisher
    ..human keratinocytes engineered to stably express the HPV-16 E7 oncoprotein exhibit aberrant Polo-like kinase 4 (PLK4) protein expression at maternal centrioles...
  84. Mason J, Lin D, Wei X, Che Y, Yao Y, Kiarash R, et al. Functional characterization of CFI-400945, a Polo-like kinase 4 inhibitor, as a potential anticancer agent. Cancer Cell. 2014;26:163-76 pubmed publisher
    b>PLK4 was identified as a promising therapeutic target through a systematic approach that combined RNAi screening with gene expression analysis in human breast cancers and cell lines...
  85. Kuriyama R, Bettencourt Dias M, Hoffmann I, Arnold M, Sandvig L. Gamma-tubulin-containing abnormal centrioles are induced by insufficient Plk4 in human HCT116 colorectal cancer cells. J Cell Sci. 2009;122:2014-23 pubmed publisher
    ..Several lines of evidence suggest that the fibers correspond to a disorganized form of centriolar microtubules. Plk4, a mammalian homolog of ZYG-1 essential for initiation of centriole biogenesis, is not associated with the gamma-..
  86. Dodson C, Yeoh S, Haq T, Bayliss R. A kinetic test characterizes kinase intramolecular and intermolecular autophosphorylation mechanisms. Sci Signal. 2013;6:ra54 pubmed publisher
    ..Whereas autophosphorylation of Nek7 and Plk4 occurred through an intermolecular mechanism, the kinases Aurora-A and Chk2 followed an intramolecular mechanism...
  87. Holland A, Fachinetti D, Zhu Q, Bauer M, Verma I, Nigg E, et al. The autoregulated instability of Polo-like kinase 4 limits centrosome duplication to once per cell cycle. Genes Dev. 2012;26:2684-9 pubmed publisher
    ..Centriole duplication occurs once per cell cycle and is controlled by Polo-like kinase 4 (Plk4). We showed previously that Plk4 phosphorylates itself to promote its degradation by the proteasome...
  88. Kerka J, Heckman D, Albert J, Sprague J, Maddox L. Statistical Modeling of the Case Information From the Ohio Attorney General's Sexual Assault Kit Testing Initiative. J Forensic Sci. 2017;: pubmed publisher
    The Ohio Attorney General's Sexual Assault Kit (SAK) Testing Initiative has resulted in nearly 14,000 kits being processed since the initiation of the project in 2012...