{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPLK4, the most structurally divergent member of the Polo‐like kinase family, functions as a master regulator of centriole duplication and centrosome biogenesis. Through both gain‐ and loss‐of‐function studies, it is clear that PLK4 initiates the assembly of daughter centrioles by coordinating the recruitment and activation of essential partners—including STIL, SAS‐6, CP110, CPAP, and Hs‐SAS6—to ensure that centrosomes are accurately reproduced once per cell cycle. These experiments, performed in diverse model systems, further highlight that disruption of PLK4 activity compromises genomic integrity and underlies aberrant cell proliferation and tumorigenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThe fidelity of centriole assembly depends not only on PLK4’s kinase activity but also on its precise spatial distribution. Key scaffold proteins—including Cep192 and Cep152—serve to recruit and anchor PLK4 at the centrosome. Recent studies elucidate that PLK4’s cryptic polo‐box domain mediates mutually exclusive interactions with these scaffolds and, together with cell cycle–regulated factors such as STIL, drives self‐organization and phase separation to delineate a unique site for daughter centriole formation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nPLK4 activity is exquisitely controlled by a series of post‐translational modifications that govern its stability and enzymatic function. Autophosphorylation drives PLK4’s trans‐activation coupled with a self-destruction mechanism mediated by ubiquitin ligases—including FBXW5 and Mib1—which in turn restrict centriole overduplication. In addition, further layers of regulation involve acetylation by lysine acetyltransferases (KAT2A/2B) as well as transcriptional repression through p53- and KLF14-dependent pathways. These modifications collectively ensure that active PLK4 is confined to centrosomal locales and that its activity is temporally coordinated with cell cycle progression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "21", "end_ref": "28"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its pivotal role in centriole biogenesis, abnormal PLK4 expression and activity have significant clinical implications. Mutations or altered expression of PLK4 have been linked to microcephalic primordial dwarfism and various cancers. Elevated PLK4 levels correlate with centrosome amplification, chromosomal instability, and enhanced tumor cell invasive behavior, whereas downregulation has been reported in certain hepatocellular carcinomas. These insights have spurred the development of targeted PLK4 inhibitors (such as CFI-400945), and genetic as well as epigenetic studies—including those identifying miRNA-mediated regulation—underscore the potential of PLK4 as a biomarker and therapeutic target."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "29", "end_ref": "38"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its canonical functions in centriole duplication, emerging evidence implicates PLK4 in non‐mitotic processes that influence cell motility and invasion. Recent studies reveal that PLK4 can regulate actin cytoskeletal dynamics by phosphorylating components of the Arp2/3 complex and by localizing to cell protrusions—activities that promote cancer cell migration and invasive behavior. Moreover, insights into a broader non‐mitotic signaling role suggest that PLK4 inhibitors may impact both cell division and interphase functions, offering novel therapeutic avenues."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "39", "end_ref": "41"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Robert Habedanck, York-Dieter Stierhof, Christopher J Wilkinson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Polo kinase Plk4 functions in centriole duplication."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb1320"}], "href": "https://doi.org/10.1038/ncb1320"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16244668"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16244668"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Julia Kleylein-Sohn, Jens Westendorf, Mikael Le Clech, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Plk4-induced centriole biogenesis in human cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Cell (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.devcel.2007.07.002"}], "href": "https://doi.org/10.1016/j.devcel.2007.07.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17681131"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17681131"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "M Bettencourt-Dias, A Rodrigues-Martins, L Carpenter, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SAK/PLK4 is required for centriole duplication and flagella development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Biol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cub.2005.11.042"}], "href": "https://doi.org/10.1016/j.cub.2005.11.042"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16326102"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16326102"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Onur Cizmecioglu, Marc Arnold, Ramona Bahtz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cep152 acts as a scaffold for recruitment of Plk4 and CPAP to the centrosome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.201007107"}], "href": "https://doi.org/10.1083/jcb.201007107"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21059844"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21059844"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Emily M Hatch, Anita Kulukian, Andrew J Holland, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cep152 interacts with Plk4 and is required for centriole duplication."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.201006049"}], "href": "https://doi.org/10.1083/jcb.201006049"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21059850"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21059850"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Midori Ohta, Tomoko Ashikawa, Yuka Nozaki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Direct interaction of Plk4 with STIL ensures formation of a single procentriole per parental centriole."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms6267"}], "href": "https://doi.org/10.1038/ncomms6267"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25342035"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25342035"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Katharina F Sonnen, Anna-Maria Gabryjonczyk, Eduard Anselm, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human Cep192 and Cep152 cooperate in Plk4 recruitment and centriole duplication."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.129502"}], "href": "https://doi.org/10.1242/jcs.129502"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23641073"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23641073"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Gernot Guderian, Jens Westendorf, Andreas Uldschmid, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Plk4 trans-autophosphorylation regulates centriole number by controlling betaTrCP-mediated degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.068502"}], "href": "https://doi.org/10.1242/jcs.068502"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20516151"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20516151"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Tae-Sung Kim, Jung-Eun Park, Anil Shukla, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hierarchical recruitment of Plk4 and regulation of centriole biogenesis by two centrosomal scaffolds, Cep192 and Cep152."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1319656110"}], "href": "https://doi.org/10.1073/pnas.1319656110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24277814"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24277814"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Tyler C Moyer, Kevin M Clutario, Bramwell G Lambrus, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Binding of STIL to Plk4 activates kinase activity to promote centriole assembly."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.201502088"}], "href": "https://doi.org/10.1083/jcb.201502088"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26101219"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26101219"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Christian Arquint, Katharina F Sonnen, York-Dieter Stierhof, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cell-cycle-regulated expression of STIL controls centriole number in human cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.099887"}], "href": "https://doi.org/10.1242/jcs.099887"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22349698"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22349698"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Christian Arquint, Erich A Nigg "}, {"type": "b", "children": [{"type": "t", "text": "The PLK4-STIL-SAS-6 module at the core of centriole duplication."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Soc Trans (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BST20160116"}], "href": "https://doi.org/10.1042/BST20160116"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27911707"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27911707"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Christian Arquint, Anna-Maria Gabryjonczyk, Stefan Imseng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "STIL binding to Polo-box 3 of PLK4 regulates centriole duplication."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.07888"}], "href": "https://doi.org/10.7554/eLife.07888"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26188084"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26188084"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "James E Sillibourne, Frederik Tack, Nele Vloemans, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Autophosphorylation of polo-like kinase 4 and its role in centriole duplication."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.e09-06-0505"}], "href": "https://doi.org/10.1091/mbc.e09-06-0505"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20032307"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20032307"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Tyler Chistopher Moyer, Andrew Jon Holland "}, {"type": "b", "children": [{"type": "t", "text": "PLK4 promotes centriole duplication by phosphorylating STIL to link the procentriole cartwheel to the microtubule wall."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.46054"}], "href": "https://doi.org/10.7554/eLife.46054"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31115335"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31115335"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Pierre Gönczy, Georgios N Hatzopoulos "}, {"type": "b", "children": [{"type": "t", "text": "Centriole assembly at a glance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.228833"}], "href": "https://doi.org/10.1242/jcs.228833"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30787112"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30787112"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Suk-Youl Park, Jung-Eun Park, Tae-Sung Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular basis for unidirectional scaffold switching of human Plk4 in centriole biogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Struct Mol Biol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nsmb.2846"}], "href": "https://doi.org/10.1038/nsmb.2846"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24997597"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24997597"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Carla A M Lopes, Swadhin Chandra Jana, Inês Cunha-Ferreira, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PLK4 trans-Autoactivation Controls Centriole Biogenesis in Space."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Cell (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.devcel.2015.09.020"}], "href": "https://doi.org/10.1016/j.devcel.2015.09.020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26481051"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26481051"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Sihem Zitouni, Maria E Francia, Filipe Leal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CDK1 Prevents Unscheduled PLK4-STIL Complex Assembly in Centriole Biogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Biol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cub.2016.03.055"}], "href": "https://doi.org/10.1016/j.cub.2016.03.055"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27112295"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27112295"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Jung-Eun Park, Liang Zhang, Jeong Kyu Bang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phase separation of Polo-like kinase 4 by autoactivation and clustering drives centriole biogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-019-12619-2"}], "href": "https://doi.org/10.1038/s41467-019-12619-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31672968"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31672968"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Anja Puklowski, Yahya Homsi, Debora Keller, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The SCF-FBXW5 E3-ubiquitin ligase is regulated by PLK4 and targets HsSAS-6 to control centrosome duplication."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb2282"}], "href": "https://doi.org/10.1038/ncb2282"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21725316"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21725316"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Andrew J Holland, Daniele Fachinetti, Quan Zhu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The autoregulated instability of Polo-like kinase 4 limits centrosome duplication to once per cell cycle."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.207027.112"}], "href": "https://doi.org/10.1101/gad.207027.112"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23249732"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23249732"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Guangjian Fan, Lianhui Sun, Peipei Shan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of KLF14 triggers centrosome amplification and tumorigenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms9450"}], "href": "https://doi.org/10.1038/ncomms9450"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26439168"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26439168"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Marjorie Fournier, Meritxell Orpinell, Cédric Grauffel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "KAT2A/KAT2B-targeted acetylome reveals a role for PLK4 acetylation in preventing centrosome amplification."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms13227"}], "href": "https://doi.org/10.1038/ncomms13227"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27796307"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27796307"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Jun Li, Mingjia Tan, Ling Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SAK, a new polo-like kinase, is transcriptionally repressed by p53 and induces apoptosis upon RNAi silencing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neoplasia (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1593/neo.04325"}], "href": "https://doi.org/10.1593/neo.04325"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15967108"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15967108"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Takanori Nakamura, Haruo Saito, Mutsuhiro Takekawa "}, {"type": "b", "children": [{"type": "t", "text": "SAPK pathways and p53 cooperatively regulate PLK4 activity and centrosome integrity under stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms2752"}], "href": "https://doi.org/10.1038/ncomms2752"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23653187"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23653187"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Lukas Čajánek, Timo Glatter, Erich A Nigg "}, {"type": "b", "children": [{"type": "t", "text": "The E3 ubiquitin ligase Mib1 regulates Plk4 and centriole biogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.166496"}], "href": "https://doi.org/10.1242/jcs.166496"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25795303"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25795303"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Rajiv C McCoy, Louise J Newnham, Christian S Ottolini, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tripolar chromosome segregation drives the association between maternal genotype at variants spanning PLK4 and aneuploidy in human preimplantation embryos."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddy147"}], "href": "https://doi.org/10.1093/hmg/ddy147"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29688390"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29688390"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Carol-Anne Martin, Ilyas Ahmad, Anna Klingseisen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in PLK4, encoding a master regulator of centriole biogenesis, cause microcephaly, growth failure and retinopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.3122"}], "href": "https://doi.org/10.1038/ng.3122"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25344692"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25344692"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Jacqueline M Mason, Dan Chi-Chia Lin, Xin Wei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional characterization of CFI-400945, a Polo-like kinase 4 inhibitor, as a potential anticancer agent."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ccr.2014.05.006"}], "href": "https://doi.org/10.1016/j.ccr.2014.05.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25043604"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25043604"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Rajiv C McCoy, Zachary Demko, Allison Ryan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Common variants spanning PLK4 are associated with mitotic-origin aneuploidy in human embryos."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.aaa3337"}], "href": "https://doi.org/10.1126/science.aaa3337"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25859044"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25859044"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Franz Meitinger, Midori Ohta, Kian-Yong Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TRIM37 controls cancer-specific vulnerability to PLK4 inhibition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41586-020-2710-1"}], "href": "https://doi.org/10.1038/s41586-020-2710-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32908304"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32908304"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Jie Bao, Yan Yu, Jianan Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-126 negatively regulates PLK-4 to impact the development of hepatocellular carcinoma via ATR/CHEK1 pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-018-1020-0"}], "href": "https://doi.org/10.1038/s41419-018-1020-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30315225"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30315225"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Lili Liu, Chris Zhiyi Zhang, Muyan Cai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Downregulation of polo-like kinase 4 in hepatocellular carcinoma associates with poor prognosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0041293"}], "href": "https://doi.org/10.1371/journal.pone.0041293"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22829937"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22829937"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Carla O Rosario, Michael A Ko, Yosr Z Haffani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Plk4 is required for cytokinesis and maintenance of chromosomal stability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0910941107"}], "href": "https://doi.org/10.1073/pnas.0910941107"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20348415"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20348415"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Nifang Niu, Yuxin Qin, Brooke L Fridley, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Radiation pharmacogenomics: a genome-wide association approach to identify radiation response biomarkers using human lymphoblastoid cell lines."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genome Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gr.107672.110"}], "href": "https://doi.org/10.1101/gr.107672.110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20923822"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20923822"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Mihaela Marina, Harold I Saavedra "}, {"type": "b", "children": [{"type": "t", "text": "Nek2 and Plk4: prognostic markers, drivers of breast tumorigenesis and drug resistance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Biosci (Landmark Ed) (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2741/4212"}], "href": "https://doi.org/10.2741/4212"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24389189"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24389189"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Peter B Sampson, Yong Liu, Narendra Kumar Patel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "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."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Chem (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/jm5005336"}], "href": "https://doi.org/10.1021/jm5005336"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24867403"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24867403"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Karineh Kazazian, Christopher Go, Hannah Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Plk4 Promotes Cancer Invasion and Metastasis through Arp2/3 Complex Regulation of the Actin Cytoskeleton."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-16-2060"}], "href": "https://doi.org/10.1158/0008-5472.CAN-16-2060"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27872092"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27872092"}]}, {"type": "r", "ref": 40, "children": [{"type": "t", "text": "C O Rosario, K Kazazian, F S W Zih, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel role for Plk4 in regulating cell spreading and motility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2014.275"}], "href": "https://doi.org/10.1038/onc.2014.275"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25174401"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25174401"}]}, {"type": "r", "ref": 41, "children": [{"type": "t", "text": "Christopher A Raab, Monika Raab, Sven Becker, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Non-mitotic functions of polo-like kinases in cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Rev Cancer (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbcan.2020.188467"}], "href": "https://doi.org/10.1016/j.bbcan.2020.188467"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33171265"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33171265"}]}]}]}