Journal articles: 'Polo kinases'

1

Archambault, Vincent, and Mar Carmena. "Polo-like kinase-activating kinases." Cell Cycle 11, no. 8 (April 15, 2012): 1490–95. http://dx.doi.org/10.4161/cc.19724.

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2

von Schubert, Conrad, and Erich A. Nigg. "Polo-like kinases." Current Biology 23, no. 6 (March 2013): R225—R227. http://dx.doi.org/10.1016/j.cub.2013.01.066.

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3

Lee, Kyung S., Tallessyn Z. Grenfell, Frederic R. Yarm, and Raymond L. Erikson. "Mutation of the polo-box disrupts localization and mitotic functions of the mammalian polo kinase Plk." Proceedings of the National Academy of Sciences 95, no. 16 (August 4, 1998): 9301–6. http://dx.doi.org/10.1073/pnas.95.16.9301.

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Members of the polo subfamily of protein kinases play pivotal roles in cell proliferation. In addition to the kinase domain, polo kinases have a strikingly conserved sequence in the noncatalytic domain, termed the polo-box. The function of the polo-box is currently undefined. The mammalian polo-like kinase Plk is a functional homologue ofSaccharomyces cerevisiaeCdc5. Here, we show that Plk localizes at the spindle poles and cytokinetic neck filaments. Without impairing kinase activity, a conservative mutation in the polo-box disrupts the capacity of Plk to complement the defect associated with acdc5–1temperature-sensitive mutation and to localize to these subcellular structures. Our data provide evidence that the polo-box plays a critical role in Plk function, likely by directing its subcellular localization.

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4

Carmena, Mar, Miguel Ortiz Lombardia, Hiromi Ogawa, and William C. Earnshaw. "Polo kinase regulates the localization and activity of the chromosomal passenger complex in meiosis and mitosis in Drosophila melanogaster." Open Biology 4, no. 11 (November 2014): 140162. http://dx.doi.org/10.1098/rsob.140162.

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Cell cycle progression is regulated by members of the cyclin-dependent kinase (CDK), Polo and Aurora families of protein kinases. The levels of expression and localization of the key regulatory kinases are themselves subject to very tight control. There is increasing evidence that crosstalk between the mitotic kinases provides for an additional level of regulation. We have previously shown that Aurora B activates Polo kinase at the centromere in mitosis, and that the interaction between Polo and the chromosomal passenger complex (CPC) component INCENP is essential in this activation. In this report, we show that Polo kinase is required for the correct localization and activity of the CPC in meiosis and mitosis. Study of the phenotype of different polo allele combinations compared to the effect of chemical inhibition revealed significant differences in the localization and activity of the CPC in diploid tissues. Our results shed new light on the mechanisms that control the activity of Aurora B in meiosis and mitosis.

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5

Garuti, L., M. Roberti, and G. Bottegoni. "Polo-Like Kinases Inhibitors." Current Medicinal Chemistry 19, no. 23 (July 1, 2012): 3937–48. http://dx.doi.org/10.2174/092986712802002455.

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6

Song, Sukgil, Tallessyn Z. Grenfell, Susan Garfield, Raymond L. Erikson, and Kyung S. Lee. "Essential Function of the Polo Box of Cdc5 in Subcellular Localization and Induction of Cytokinetic Structures." Molecular and Cellular Biology 20, no. 1 (January 1, 2000): 286–98. http://dx.doi.org/10.1128/mcb.20.1.286-298.2000.

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ABSTRACT Members of the polo subfamily of protein kinases play pivotal roles in cell proliferation. In addition to the kinase domain, polo kinases have a strikingly conserved sequence in the noncatalytic C-terminal domain, termed the polo box. Here we show that the budding-yeast polo kinase Cdc5, when fused to green fluorescent protein and expressed under its endogenous promoter, localizes at spindle poles and the mother bud neck. Overexpression of Cdc5 can induce a class of cells with abnormally elongated buds in a polo box- and kinase activity-dependent manner. In addition to localizing at the spindle poles and cytokinetic neck filaments, Cdc5 induces and localizes to additional septin ring structures within the elongated buds. Without impairing kinase activity, conservative mutations in the polo box abolish the ability of Cdc5 to functionally complement the defect associated with a cdc5-1 temperature-sensitive mutation, to localize to the spindle poles and cytokinetic neck filaments, and to induce elongated cells with ectopic septin ring structures. Consistent with the polo box-dependent subcellular localization, the C-terminal domain of Cdc5, but not its polo box mutant, is sufficient for subcellular localization, and its overexpression appears to inhibit cytokinesis. These data provide evidence that the polo box is required to direct Cdc5 to specific subcellular locations and induce or organize cytokinetic structures.

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7

Dai, Wei. "Polo-like kinases, an introduction." Oncogene 24, no. 2 (January 2005): 214–16. http://dx.doi.org/10.1038/sj.onc.1208270.

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8

Eckerdt, Frank, Juping Yuan, and Klaus Strebhardt. "Polo-like kinases and oncogenesis." Oncogene 24, no. 2 (January 2005): 267–76. http://dx.doi.org/10.1038/sj.onc.1208273.

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9

Berg, Tobias, Gesine Bug, Oliver G. Ottmann, and Klaus Strebhardt. "Polo-like kinases in AML." Expert Opinion on Investigational Drugs 21, no. 8 (June 6, 2012): 1069–74. http://dx.doi.org/10.1517/13543784.2012.691163.

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10

Hagan, Iain M. "The spindle pole body plays a key role in controlling mitotic commitment in the fission yeast Schizosaccharomyces pombe." Biochemical Society Transactions 36, no. 5 (September 19, 2008): 1097–101. http://dx.doi.org/10.1042/bst0361097.

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Commitment to mitosis is regulated by a conserved protein kinase complex called MPF (mitosis-promoting factor). MPF activation triggers a positive-feedback loop that further promotes the activity of its activating phosphatase Cdc25 and is assumed to down-regulate the MPF-inhibitory kinase Wee1. Four protein kinases contribute to this amplification loop: MPF itself, Polo kinase, MAPK (mitogen-activated protein kinase) and Greatwall kinase. The fission yeast SPB (spindle pole body) component Cut12 plays a critical role in modulating mitotic commitment. In this review, I discuss the relationship between Cut12 and the fission yeast Polo kinase Plo1 in mitotic control. These results indicate that commitment to mitosis is co-ordinated by control networks on the spindle pole. I then describe how the Cut12/Plo1 control network links growth control signalling from TOR (target of rapamycin) and MAPK networks to the activation of MPF to regulate the timing of cell division.

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11

Liu, Yongsheng, Ning Jiang, Jiangyue Wu, Wei Dai, and Jonathan S. Rosenblum. "Polo-like Kinases Inhibited by Wortmannin." Journal of Biological Chemistry 282, no. 4 (November 29, 2006): 2505–11. http://dx.doi.org/10.1074/jbc.m609603200.

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12

Dai, Wei, Qi Wang, and Frank Traganos. "Polo-like kinases and centrosome regulation." Oncogene 21, no. 40 (September 2002): 6195–200. http://dx.doi.org/10.1038/sj.onc.1205710.

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13

Goroshchuk, Oksana, Iryna Kolosenko, Linda Vidarsdottir, Alireza Azimi, and Caroline Palm-Apergi. "Polo-like kinases and acute leukemia." Oncogene 38, no. 1 (August 13, 2018): 1–16. http://dx.doi.org/10.1038/s41388-018-0443-5.

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14

Takai, Noriyuki, Ryoji Hamanaka, Jun Yoshimatsu, and Isao Miyakawa. "Polo-like kinases (Plks) and cancer." Oncogene 24, no. 2 (January 2005): 287–91. http://dx.doi.org/10.1038/sj.onc.1208272.

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15

Woo, Sang-Uk, Hay-Ran Jang, Young-Won Chin, and Hyungshin Yim. "7-O-Methylwogonin from Scutellaria baicalensis Disturbs Mitotic Progression by Inhibiting Plk1 Activity in Hep3B Cells." Planta Medica 85, no. 03 (September 10, 2018): 217–24. http://dx.doi.org/10.1055/a-0731-0394.

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AbstractPolo-like kinase 1, a mitotic Ser/Thr kinase, has emerged as a molecular target for the development of anticancer drugs. In this study, we found that polo-like kinase 1 activity was inhibited by 7-O-methylwogonin and related flavones, including baicalein, dihydrobaicalein, and viscidulin II, isolated from Scutellaria baicalensis. Although dihydrobaicalein exhibited the highest polo-like kinase 1 inhibitory activity among the four compounds, it also inhibited other kinases, such as vaccinia-related kinase 2 and polo-like kinase 2. Baicalein and viscidulin II also showed low selectivity to polo-like kinase 1 since they inhibited polo-like kinase 3 and polo-like kinase 2, respectively. However, 7-O-methylwogonin exhibited selective polo-like kinase 1 inhibitory activity, as evidenced from in vitro kinase assays based on fluorescence resonance energy transfer assays and ADP-Glo kinase assays. In addition, examination of mitotic morphology and immunostaining using specific antibodies for the mitotic markers, p-histone H3 and mitotic protein monoclonal 2, in Hep3B cells showed that 7-O-methylwogonin treatment increased mitotic cell populations due to inhibition of mitotic progression as a result of polo-like kinase 1 inhibition. The pattern of 7-O-methylwogonin-induced mitotic arrest was similar to that of BI 2536, a specific polo-like kinase 1 inhibitor. Thus, it was suggested that 7-O-methylwogonin disturbed mitotic progression by inhibiting polo-like kinase 1 activity. These data suggest that 7-O-methylwogonin, a polo-like kinase 1 inhibitor, may be a useful anticancer agent because of its polo-like kinase 1 selectivity and effectiveness.

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16

Jani, Krupa S., and D. S. Dalafave. "Computational Design of Targeted Inhibitors of Polo-Like Kinase 1 (Plk1)." Bioinformatics and Biology Insights 6 (January 2012): BBI.S8971. http://dx.doi.org/10.4137/bbi.s8971.

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Computational design of small molecule putative inhibitors of Polo-like kinase 1 (Plk1) is presented. Plk1, which regulates the cell cycle, is often over expressed in cancers. Down regulation of Plk1 has been shown to inhibit tumor progression. Most kinase inhibitors interact with the ATP binding site on Plk1, which is highly conserved. This makes the development of Plk1-specific inhibitors challenging, since different kinases have similar ATP sites. However, Plk1 also contains a unique region called the polo-box domain (PBD), which is absent from other kinases. In this study, the PBD site was used as a target for designed Plk1 putative inhibitors. Common structural features of several experimentally known Plk1 ligands were first identified. The findings were used to design small molecules that specifically bonded Plk1. Drug likeness and possible toxicities of the molecules were investigated. Molecules with no implied toxicities and optimal drug likeness values were used for docking studies. Several molecules were identified that made stable complexes only with Plk1 and LYN kinases, but not with other kinases. One molecule was found to bind exclusively the PBD site of Plk1. Possible utilization of the designed molecules in drugs against cancers with over expressed Plk1 is discussed.

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17

May, Karen M., Nicola Reynolds, C. Fiona Cullen, Mitsuhiro Yanagida, and Hiroyuki Ohkura. "Polo boxes and Cut23 (Apc8) mediate an interaction between polo kinase and the anaphase-promoting complex for fission yeast mitosis." Journal of Cell Biology 156, no. 1 (January 3, 2002): 23–28. http://dx.doi.org/10.1083/jcb.200106150.

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The fission yeast plo1+ gene encodes a polo-like kinase, a member of a conserved family of kinases which play multiple roles during the cell cycle. We show that Plo1 kinase physically interacts with the anaphase-promoting complex (APC)/cyclosome through the noncatalytic domain of Plo1 and the tetratricopeptide repeat domain of the subunit, Cut23. A new cut23 mutation, which specifically disrupts the interaction with Plo1, results in a metaphase arrest. This arrest can be rescued by high expression of Plo1 kinase. We suggest that this physical interaction is crucial for mitotic progression by targeting polo kinase activity toward the APC.

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18

Preisinger, Christian, and Francis A. Barr. "Kinases regulating Golgi apparatus structure and function." Biochemical Society Symposia 72 (January 1, 2005): 15–30. http://dx.doi.org/10.1042/bss0720015.

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Protein kinases control Golgi function in both mitotic and interphase cells. In mitosis, phosphorylation of structural proteins by Cdk1 (cyclin-dependent kinase 1)-cyclin B, Polo-like and mitogen-activated protein kinases underlie changes in Golgi reorganization during cell division. While in interphase, signalling pathways that are associated with the Golgi control secretory function through a variety of mechanisms. Some of these, notably those involving protein kinase D and Ste20 family kinases, are also relevant for the establishment and maintenance of cell polarization and migration.

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19

Mulvihill, Daniel P., Janni Petersen, Hiroyuki Ohkura, David M. Glover, and Iain M. Hagan. "Plo1 Kinase Recruitment to the Spindle Pole Body and Its Role in Cell Division inSchizosaccharomyces pombe." Molecular Biology of the Cell 10, no. 8 (August 1999): 2771–85. http://dx.doi.org/10.1091/mbc.10.8.2771.

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Polo kinases execute multiple roles during cell division. The fission yeast polo related kinase Plo1 is required to assemble the mitotic spindle, the prophase actin ring that predicts the site for cytokinesis and for septation after the completion of mitosis ( Ohkuraet al., 1995 ; Bahler et al., 1998 ). We show that Plo1 associates with the mitotic but not interphase spindle pole body (SPB). SPB association of Plo1 is the earliest fission yeast mitotic event recorded to date. SPB association is strong from mitotic commitment to early anaphase B, after which the Plo1 signal becomes very weak and finally disappears upon spindle breakdown. SPB association of Plo1 requires mitosis-promoting factor (MPF) activity, whereas its disassociation requires the activity of the anaphase-promoting complex. The stf1.1 mutation bypasses the usual requirement for the MPF activator Cdc25 ( Hudson et al., 1990 ). Significantly, Plo1 associates inappropriately with the interphase SPB of stf1.1 cells. These data are consistent with the emerging theme from many systems that polo kinases participate in the regulation of MPF to determine the timing of commitment to mitosis and may indicate that pole association is a key aspect of Plo1 function. Plo1 does not associate with the SPB when septation is inappropriately driven by deregulation of the Spg1 pathway and remains SPB associated if septation occurs in the presence of a spindle. Thus, neither Plo1 recruitment to nor its departure from the SPB are required for septation; however, overexpression ofplo1+activates the Spg1 pathway and causes transient Cdc7 recruitment to the SPB and multiple rounds of septation.

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20

Seeburg, Daniel P., Daniel Pak, and Morgan Sheng. "Polo-like kinases in the nervous system." Oncogene 24, no. 2 (January 2005): 292–98. http://dx.doi.org/10.1038/sj.onc.1208277.

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21

Lowery, Drew M., Daniel Lim, and Michael B. Yaffe. "Structure and function of Polo-like kinases." Oncogene 24, no. 2 (January 2005): 248–59. http://dx.doi.org/10.1038/sj.onc.1208280.

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22

WARNER, S., P. GRAY, and D. VONHOFF. "Tubulin-Associated Drug Targets: Aurora Kinases, Polo-like Kinases, and Others." Seminars in Oncology 33, no. 4 (August 2006): 436–48. http://dx.doi.org/10.1053/j.seminoncol.2006.04.007.

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23

Gallaud, Emmanuel, Laurent Richard-Parpaillon, Laetitia Bataillé, Aude Pascal, Mathieu Métivier, Vincent Archambault, and Régis Giet. "The spindle assembly checkpoint and the spatial activation of Polo kinase determine the duration of cell division and prevent tumor formation." PLOS Genetics 18, no. 4 (April 4, 2022): e1010145. http://dx.doi.org/10.1371/journal.pgen.1010145.

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The maintenance of a restricted pool of asymmetrically dividing stem cells is essential for tissue homeostasis. This process requires the control of mitotic progression that ensures the accurate chromosome segregation. In addition, this event is coupled to the asymmetric distribution of cell fate determinants in order to prevent stem cell amplification. How this coupling is regulated remains poorly described. Here, using asymmetrically dividing Drosophila neural stem cells (NSCs), we show that Polo kinase activity levels determine timely Cyclin B degradation and mitotic progression independent of the spindle assembly checkpoint (SAC). This event is mediated by the direct phosphorylation of Polo kinase by Aurora A at spindle poles and Aurora B kinases at centromeres. Furthermore, we show that Aurora A-dependent activation of Polo is the major event that promotes NSC polarization and together with the SAC prevents brain tumor growth. Altogether, our results show that an Aurora/Polo kinase module couples NSC mitotic progression and polarization for tissue homeostasis.

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Kurasawa, Yasuhiro, Tai An, and Ziyin Li. "Polo-like kinase in trypanosomes: an odd member out of the Polo family." Open Biology 10, no. 10 (October 2020): 200189. http://dx.doi.org/10.1098/rsob.200189.

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Polo-like kinases (Plks) are evolutionarily conserved serine/threonine protein kinases playing crucial roles during multiple stages of mitosis and cytokinesis in yeast and animals. Plks are characterized by a unique Polo-box domain, which plays regulatory roles in controlling Plk activation, interacting with substrates and targeting Plk to specific subcellular locations. Plk activity and protein abundance are subject to temporal and spatial control through transcription, phosphorylation and proteolysis. In the early branching protists, Plk orthologues are present in some taxa, such as kinetoplastids and Giardia , but are lost in apicomplexans, such as Plasmodium . Works from characterizing a Plk orthologue in Trypanosoma brucei , a kinetoplastid protozoan, discover its essential roles in regulating the inheritance of flagellum-associated cytoskeleton and the initiation of cytokinesis, but not any stage of mitosis. These studies reveal evolutionarily conserved and species-specific features in the control of Plk activation, substrate recognition and protein abundance, and suggest the divergence of Plk function and regulation for specialized needs in this flagellated unicellular eukaryote.

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25

Bimbó, Andrea, Jianhua Liu, and Mohan K. Balasubramanian. "Roles of Pdk1p, a Fission Yeast Protein Related to Phosphoinositide-dependent Protein Kinase, in the Regulation of Mitosis and Cytokinesis." Molecular Biology of the Cell 16, no. 7 (July 2005): 3162–75. http://dx.doi.org/10.1091/mbc.e04-09-0769.

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Proteins related to the phosphoinositide-dependent protein kinase family have been identified in the majority of eukaryotes. Although much is known about upstream mechanisms that regulate the PDK1-family of kinases in metazoans, how these kinases regulate cell growth and division remains unclear. Here, we characterize a fission yeast protein related to members of this family, which we have termed Pdk1p. Pdk1p localizes to the spindle pole body and the actomyosin ring in early mitotic cells. Cells deleted for pdk1 display multiple defects in mitosis and cytokinesis, all of which are exacerbated when the function of fission yeast polo kinase, Plo1p, is partially compromised. We conclude that Pdk1p functions in concert with Plo1p to regulate multiple processes such as the establishment of a bipolar mitotic spindle, transition to anaphase, placement of the actomyosin ring and proper execution of cytokinesis. We also present evidence that the effects of Pdk1p on cytokinesis are likely mediated via the fission yeast anillin-related protein, Mid1p, and the septation initiation network.

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Hardy, C. F., and A. Pautz. "A novel role for Cdc5p in DNA replication." Molecular and Cellular Biology 16, no. 12 (December 1996): 6775–82. http://dx.doi.org/10.1128/mcb.16.12.6775.

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DNA replication initiates from specific chromosomal sites called origins, and in the budding yeast Saccharomyces cerevisiae these sites are occupied by the origin recognition complex (ORC). Dbf4p is proposed to play a role in targeting the G1/S kinase Cdc7p to initiation complexes late in G1. We report that Dbf4p may also recruit Cdc5p to origin complexes. Cdc5p is a member of the Polo family of kinases that is required for the completion of mitosis. Cdc5p and Cdc7p each interact with a distinct domain of Dbf4p. cdc5-1 mutants have a plasmid maintenance defect that can be suppressed by the addition of multiple origins. cdc5-1 orc2-1 double mutants are synthetically lethal. Levels of Cdc5p were found to be cell cycle regulated and peaked in G2/M. These results suggest a role for Cdc5p and possibly Polo-like kinases at origin complexes.

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27

Dai, Wei. "Polo-like kinases in cell cycle checkpoint control." Frontiers in Bioscience 8, no. 4 (2003): d1128–1133. http://dx.doi.org/10.2741/1129.

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28

Townsley, F. "A destructive role for the Polo-like kinases." Trends in Cell Biology 8, no. 6 (June 1, 1998): 222. http://dx.doi.org/10.1016/s0962-8924(98)01294-x.

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29

Brose, Lotti, Justin Crest, Li Tao, and William Sullivan. "Polo kinase mediates the phosphorylation and cellular localization of Nuf/FIP3, a Rab11 effector." Molecular Biology of the Cell 28, no. 11 (June 2017): 1435–43. http://dx.doi.org/10.1091/mbc.e16-04-0236.

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Animal cytokinesis involves both actin-myosin–based contraction and vesicle-mediated membrane addition. In many cell types, including early Drosophila embryos, Nuf/FIP3, a Rab11 effector, mediates recycling endosome (RE)–based vesicle delivery to the cytokinesis furrow. Nuf exhibits a cell cycle–regulated concentration at the centrosome that is accompanied by dramatic changes in its phosphorylation state. Here we demonstrate that maximal phosphorylation of Nuf occurs at prophase, when centrosome-associated Nuf disperses throughout the cytoplasm. Accordingly, ectopic Cdk1 activation results in immediate Nuf dispersal from the centrosome. Screening of candidate kinases reveals a specific, dosage-sensitive interaction between Nuf and Polo with respect to Nuf-mediated furrow formation. Inhibiting Polo activity results in Nuf underphosphorylation and prolonged centrosome association. In vitro, Polo directly binds and is required for Nuf phosphorylation at Ser-225 and Thr-227, matching previous in vivo–mapped phosphorylation sites. These results demonstrate a role for Polo kinase in directly mediating Nuf cell cycle–dependent localization.

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30

Lens, Susanne M. A., Emile E. Voest, and René H. Medema. "Shared and separate functions of polo-like kinases and aurora kinases in cancer." Nature Reviews Cancer 10, no. 12 (November 24, 2010): 825–41. http://dx.doi.org/10.1038/nrc2964.

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31

Javed, Aadil, Gianluca Malagraba, Mahdieh Yarmohammadi, Catalina M. Perelló-Reus, Carles Barceló, and Teresa Rubio-Tomás. "Therapeutic Potential of Mitotic Kinases’ Inhibitors in Cancers of the Gastrointestinal System." Future Pharmacology 2, no. 3 (June 30, 2022): 214–37. http://dx.doi.org/10.3390/futurepharmacol2030015.

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Mitosis entails mechanistic changes required for maintaining the genomic integrity in all dividing cells. The process is intricate and temporally and spatially regulated by the ordered series of activation and de-activation of protein kinases. The mitotic kinases ensure the stepwise progression of entry into mitosis after the G2 phase of the cell cycle, followed by prophase, pro-metaphase, metaphase, anaphase, telophase, and subsequently cytokinesis and birth of two daughter cells with equal segregation and distribution of the genome. The major mitotic kinases include cyclin-dependent kinase 1 (CDK1), Aurora A and B Kinases, and Polo-Like-Kinase 1 (PLK1), among others. Overexpression of some of these kinases has been reported in many cancers as the mitotic fidelity and genome integrity are interlinked and dependent on these regulators, the native irregularities in these factors can be targeted as therapeutic strategies for various cancers. Here, we report and summarize the recent updates on the literature describing the various mitotic inhibitors targeting kinases, which can be used as potential therapeutic interventions for gastrointestinal cancers including gastric cancer, liver cancer, pancreatic cancer and colorectal cancer.

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32

Cheng, Liang, Linda Hunke, and Christopher F. J. Hardy. "Cell Cycle Regulation of the Saccharomyces cerevisiae Polo-Like Kinase Cdc5p." Molecular and Cellular Biology 18, no. 12 (December 1, 1998): 7360–70. http://dx.doi.org/10.1128/mcb.18.12.7360.

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ABSTRACT Progression through and completion of mitosis require the actions of the evolutionarily conserved Polo kinase. We have determined that the levels of Cdc5p, a Saccharomyces cerevisiae member of the Polo family of mitotic kinases, are cell cycle regulated. Cdc5p accumulates in the nuclei of G2/M-phase cells, and its levels decline dramatically as cells progress through anaphase and begin telophase. We report that Cdc5p levels are sensitive to mutations in key components of the anaphase-promoting complex (APC). We have determined that Cdc5p-associated kinase activity is restricted to G2/M and that this activity is posttranslationally regulated. These results further link the actions of the APC to the completion of mitosis and suggest possible roles for Cdc5p during progression through and completion of mitosis.

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33

Zheng, Yingfeng, and Leigh C. Murphy. "Regulation of Steroid Hormone Receptors and Coregulators during the Cell Cycle Highlights Potential Novel Function in Addition to Roles as Transcription Factors." Nuclear Receptor Signaling 14, no. 1 (January 2016): nrs.14001. http://dx.doi.org/10.1621/nrs.14001.

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Cell cycle progression is tightly controlled by several kinase families including Cyclin-Dependent Kinases, Polo-Like Kinases, and Aurora Kinases. A large amount of data show that steroid hormone receptors and various components of the cell cycle, including cell cycle regulated kinases, interact, and this often results in altered transcriptional activity of the receptor. Furthermore, steroid hormones, through their receptors, can also regulate the transcriptional expression of genes that are required for cell cycle regulation. However, emerging data suggest that steroid hormone receptors may have roles in cell cycle progression independent of their transcriptional activity. The following is a review of how steroid receptors and their coregulators can regulate or be regulated by the cell cycle machinery, with a particular focus on roles independent of transcription in G2/M.

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34

Golsteyn, R. M., S. J. Schultz, J. Bartek, A. Ziemiecki, T. Ried, and E. A. Nigg. "Cell cycle analysis and chromosomal localization of human Plk1, a putative homologue of the mitotic kinases Drosophila polo and Saccharomyces cerevisiae Cdc5." Journal of Cell Science 107, no. 6 (June 1, 1994): 1509–17. http://dx.doi.org/10.1242/jcs.107.6.1509.

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polo and CDC5 are two genes required for passage through mitosis in Drosophila melanogaster and Saccharomyces cerevisiae, respectively. Both genes encode structurally related protein kinases that have been implicated in regulating the function of the mitotic spindle. Here, we report the characterization of a human protein kinase that displays extensive sequence similarity to Drosophila polo and S. cerevisiae Cdc5; we refer to this kinase as Plk1 (for polo-like kinase 1). The largest open reading frame of the Plk1 cDNA encodes a protein of 68,254 daltons, and a protein of this size is detected by immunoblotting of HeLa cell extracts with monoclonal antibodies raised against the C-terminal part of Plk1 expressed in Escherichia coli. Northern blot analysis of RNA isolated from human cells and mouse tissues shows that a single Plk1 mRNA of 2.3 kb is highly expressed in tissues with a high mitotic index, consistent with a possible function of Plk1 in cell proliferation. The Plk1 gene maps to position p12 on chromosome 16, a locus for which no associations with neoplastic malignancies are known. The Plk1 protein levels and its distribution change during the cell cycle, in a manner consistent with a role of Plk1 in mitosis. Thus, like Drosophila polo and S. cerevisiae Cdc5, human Plk1 is likely to function in cell cycle progression.

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35

Pereira Moreira, Bernardo, Michael H. W. Weber, Simone Haeberlein, Annika S. Mokosch, Bernhard Spengler, Christoph G. Grevelding, and Franco H. Falcone. "Drug Repurposing and De Novo Drug Discovery of Protein Kinase Inhibitors as New Drugs against Schistosomiasis." Molecules 27, no. 4 (February 19, 2022): 1414. http://dx.doi.org/10.3390/molecules27041414.

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Schistosomiasis is a neglected tropical disease affecting more than 200 million people worldwide. Chemotherapy relies on one single drug, praziquantel, which is safe but ineffective at killing larval stages of this parasite. Furthermore, concerns have been expressed about the rise in resistance against this drug. In the absence of an antischistosomal vaccine, it is, therefore, necessary to develop new drugs against the different species of schistosomes. Protein kinases are important molecules involved in key cellular processes such as signaling, growth, and differentiation. The kinome of schistosomes has been studied and the suitability of schistosomal protein kinases as targets demonstrated by RNA interference studies. Although protein kinase inhibitors are mostly used in cancer therapy, e.g., for the treatment of chronic myeloid leukemia or melanoma, they are now being increasingly explored for the treatment of non-oncological conditions, including schistosomiasis. Here, we discuss the various approaches including screening of natural and synthetic compounds, de novo drug development, and drug repurposing in the context of the search for protein kinase inhibitors against schistosomiasis. We discuss the status quo of the development of kinase inhibitors against schistosomal serine/threonine kinases such as polo-like kinases (PLKs) and mitogen-activated protein kinases (MAP kinases), as well as protein tyrosine kinases (PTKs).

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Dodson, Charlotte A., Tamanna Haq, Sharon Yeoh, Andrew M. Fry, and Richard Bayliss. "The structural mechanisms that underpin mitotic kinase activation." Biochemical Society Transactions 41, no. 4 (July 18, 2013): 1037–41. http://dx.doi.org/10.1042/bst20130066.

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In eukaryotic cells, the peak of protein phosphorylation occurs during mitosis, switching the activities of a significant proportion of proteins and orchestrating a wholesale reorganization of cell shape and internal architecture. Most mitotic protein phosphorylation events are catalysed by a small subset of serine/threonine protein kinases. These include members of the Cdk (cyclin-dependent kinase), Plk (Polo-like kinase), Aurora, Nek (NimA-related kinase) and Bub families, as well as Haspin, Greatwall and Mps1/TTK. There has been steady progress in resolving the structural mechanisms that regulate the catalytic activities of these mitotic kinases. From structural and biochemical perspectives, kinase activation appears not as a binary process (from inactive to active), but as a series of states that exhibit varying degrees of activity. In its lowest activity state, a mitotic kinase may exhibit diverse autoinhibited or inactive conformations. Kinase activation proceeds via phosphorylation and/or association with a binding partner. These remodel the structure into an active conformation that is common to almost all protein kinases. However, all mitotic kinases of known structure have divergent features, many of which are key to understanding their specific regulatory mechanisms. Finally, mitotic kinases are an important class of drug target, and their structural characterization has facilitated the rational design of chemical inhibitors.

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Li, Jingjing, Myung Jin Hong, Jeremy P. H. Chow, Wing Yu Man, Joyce P. Y. Mak, Hoi Tang Ma, and Randy Y. C. Poon. "Co-inhibition of polo-like kinase 1 and Aurora kinases promotes mitotic catastrophe." Oncotarget 6, no. 11 (March 20, 2015): 9327–40. http://dx.doi.org/10.18632/oncotarget.3313.

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Xia, Jiliang, Reinaldo Franqui Machin, Zhimin Gu, and Fenghuang Zhan. "Role of NEK2A in Human Cancer and Its Therapeutic Potentials." BioMed Research International 2015 (2015): 1–12. http://dx.doi.org/10.1155/2015/862461.

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Chromosome instability (CIN) has been identified as a common feature of most human cancers. A number of centrosomal kinases are thought to cause CIN in cancer cells. Part of those centrosomal kinases exhibit elevated expression in a wide variety of tumours and cancer cell lines. Additionally, critical roles in many aspects of cancer cell growth, proliferation, metastasis, and drug resistance have been assigned to some of these centrosomal kinases, such as polo-like kinase 1 (PLk1) and Aurora-A kinase. Recent studies from our group and others revealed that a centrosomal kinase, Never in Mitosis (NIMA) Related Kinase 2A (NEK2A), is frequently upregulated in multiple types of human cancers. Uncontrolled activity of NEK2A activates several oncogenic pathways and ABC transporters, thereby leading to CIN, cancer cell proliferation, metastasis, and enhanced drug resistance. In this paper, we highlight recent findings on the aberrant expression and functional significance of NEK2A in human cancers and emphasize their significance for therapeutic potentials.

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Riparbelli, M. G., G. Callaini, and D. M. Glover. "Failure of pronuclear migration and repeated divisions of polar body nuclei associated with MTOC defects in polo eggs of Drosophila." Journal of Cell Science 113, no. 18 (September 15, 2000): 3341–50. http://dx.doi.org/10.1242/jcs.113.18.3341.

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The meiotic spindle of Drosophila oocytes is acentriolar but develops an unusual central microtubule organising centre (MTOC) at the end of meiosis I. In polo oocytes, this common central pole for the two tandem spindles of meiosis II was poorly organised and in contrast to wild-type failed to maintain its associated Pav-KLP motor protein. Furthermore, the polar body nuclei failed to arrest at metaphase, and the four products of female meiosis all underwent repeated haploid division cycles on anastral spindles. This was linked to a failure to form the astral array of microtubules with which the polar body chromosomes are normally associated. The MTOC associated with the male pronucleus was also defective in polo eggs, and the sperm aster did not grow. Migration of the female pronucleus did not take place and so a gonomeric spindle could not form. We discuss these findings in relation to the known roles of polo like kinases in regulating the behaviour of MTOCs.

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Ma, Hoi Tang, and Randy Y. C. Poon. "How protein kinases co-ordinate mitosis in animal cells." Biochemical Journal 435, no. 1 (March 15, 2011): 17–31. http://dx.doi.org/10.1042/bj20100284.

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Mitosis is associated with profound changes in cell physiology and a spectacular surge in protein phosphorylation. To accomplish these, a remarkably large portion of the kinome is involved in the process. In the present review, we will focus on classic mitotic kinases, such as cyclin-dependent kinases, Polo-like kinases and Aurora kinases, as well as more recently characterized players such as NIMA (never in mitosis in Aspergillus nidulans)-related kinases, Greatwall and Haspin. Together, these kinases co-ordinate the proper timing and fidelity of processes including centrosomal functions, spindle assembly and microtubule–kinetochore attachment, as well as sister chromatid separation and cytokinesis. A recurrent theme of the mitotic kinase network is the prevalence of elaborated feedback loops that ensure bistable conditions. Sequential phosphorylation and priming phosphorylation on substrates are also frequently employed. Another important concept is the role of scaffolds, such as centrosomes for protein kinases during mitosis. Elucidating the entire repertoire of mitotic kinases, their functions, regulation and interactions is critical for our understanding of normal cell growth and in diseases such as cancers.

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Zitouni, Sihem, Catarina Nabais, Swadhin Chandra Jana, Adán Guerrero, and Mónica Bettencourt-Dias. "Polo-like kinases: structural variations lead to multiple functions." Nature Reviews Molecular Cell Biology 15, no. 7 (June 23, 2014): 433–52. http://dx.doi.org/10.1038/nrm3819.

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Glover, D. M., I. M. Hagan, and A. A. M. Tavares. "Polo-like kinases: a team that plays throughout mitosis." Genes & Development 12, no. 24 (December 15, 1998): 3777–87. http://dx.doi.org/10.1101/gad.12.24.3777.

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Matsumoto, T., P. y. Wang, W. Ma, H. J. Sung, S. Matoba, and P. M. Hwang. "Polo-like kinases mediate cell survival in mitochondrial dysfunction." Proceedings of the National Academy of Sciences 106, no. 34 (August 11, 2009): 14542–46. http://dx.doi.org/10.1073/pnas.0904229106.

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Taylor, Stephen, and Jan-Michael Peters. "Polo and Aurora kinases—lessons derived from chemical biology." Current Opinion in Cell Biology 20, no. 1 (February 2008): 77–84. http://dx.doi.org/10.1016/j.ceb.2007.11.008.

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Xie, Suqing, Bin Xie, Marietta Y. Lee, and Wei Dai. "Regulation of cell cycle checkpoints by polo-like kinases." Oncogene 24, no. 2 (January 2005): 277–86. http://dx.doi.org/10.1038/sj.onc.1208218.

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Lee, Kyung S., Jung-Eun Park, Satoshi Asano, and Chong J. Park. "Yeast polo-like kinases: functionally conserved multitask mitotic regulators." Oncogene 24, no. 2 (January 2005): 217–29. http://dx.doi.org/10.1038/sj.onc.1208271.

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Barr, Francis A., Herman H. W. Silljé, and Erich A. Nigg. "Polo-like kinases and the orchestration of cell division." Nature Reviews Molecular Cell Biology 5, no. 6 (June 2004): 429–41. http://dx.doi.org/10.1038/nrm1401.

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Bucko, Paula J., Irvin Garcia, Ridhima Manocha, Akansha Bhat, Linda Wordeman, and John D. Scott. "Gravin-associated kinase signaling networks coordinate γ-tubulin organization at mitotic spindle poles." Journal of Biological Chemistry 295, no. 40 (July 30, 2020): 13784–97. http://dx.doi.org/10.1074/jbc.ra120.014791.

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Mitogenic signals that regulate cell division often proceed through multienzyme assemblies within defined intracellular compartments. The anchoring protein Gravin restricts the action of mitotic kinases and cell-cycle effectors to defined mitotic structures. In this report we discover that genetic deletion of Gravin disrupts proper accumulation and asymmetric distribution of γ-tubulin during mitosis. We utilize a new precision pharmacology tool, Local Kinase Inhibition, to inhibit the Gravin binding partner polo-like kinase 1 at spindle poles. Using a combination of gene-editing approaches, quantitative imaging, and biochemical assays, we provide evidence that disruption of local polo-like kinase 1 signaling underlies the γ-tubulin distribution defects observed with Gravin loss. Our study uncovers a new role for Gravin in coordinating γ-tubulin recruitment during mitosis and illuminates the mechanism by which signaling enzymes regulate this process at a distinct subcellular location.

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Park, Chong J., Jung-Eun Park, Tatiana S. Karpova, Nak-Kyun Soung, Li-Rong Yu, Sukgil Song, Kyung H. Lee, et al. "Requirement for the Budding Yeast Polo Kinase Cdc5 in Proper Microtubule Growth and Dynamics." Eukaryotic Cell 7, no. 3 (January 4, 2008): 444–53. http://dx.doi.org/10.1128/ec.00283-07.

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ABSTRACT In many organisms, polo kinases appear to play multiple roles during M-phase progression. To provide new insights into the function of the budding yeast polo kinase Cdc5, we generated novel temperature-sensitive cdc5 mutants by mutagenizing the C-terminal noncatalytic polo box domain, a region that is critical for proper subcellular localization. One of these mutants, cdc5-11, exhibited a temperature-sensitive growth defect with an abnormal spindle morphology. Strikingly, provision of a moderate level of benomyl, a microtubule-depolymerizing drug, permitted cdc5-11 cells to grow significantly better than the isogenic CDC5 wild type in a FEAR (cdc Fourteen Early Anaphase Release)-independent manner. In addition, cdc5-11 required MAD2 for both cell growth and the benomyl-remedial phenotype. These results suggest that cdc5-11 is defective in proper spindle function. Consistent with this view, cdc5-11 exhibited abnormal spindle morphology, shorter spindle length, and delayed microtubule regrowth at the nonpermissive temperature. Overexpression of CDC5 moderately rescued the spc98-2 growth defect. Interestingly, both Cdc28 and Cdc5 were required for the proper modification of the spindle pole body components Nud1, Slk19, and Stu2 in vivo. They also phosphorylated these three proteins in vitro. Taken together, these observations suggest that concerted action of Cdc28 and Cdc5 on Nud1, Slk19, and Stu2 is important for proper spindle functions.

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Pickar, Adrian, James Zengel, Pei Xu, Zhuo Li, and Biao He. "Mumps Virus Nucleoprotein Enhances Phosphorylation of the Phosphoprotein by Polo-Like Kinase 1." Journal of Virology 90, no. 3 (November 25, 2015): 1588–98. http://dx.doi.org/10.1128/jvi.02160-15.

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ABSTRACTThe viral RNA-dependent RNA polymerases (vRdRps) of nonsegmented, negative-sense viruses (NNSVs) consist of the enzymatic large protein (L) and the phosphoprotein (P). P is heavily phosphorylated, and its phosphorylation plays a critical role in viral RNA synthesis. Since NNSVs do not encode kinases, P is phosphorylated by host kinases. In this study, we investigate the roles that viral proteins play in the phosphorylation of mumps virus (MuV) P. We found that nucleoprotein (NP) enhances the phosphorylation of P. We have identified the serine/threonine kinase Polo-like kinase 1 (PLK1) as a host kinase that phosphorylates P and have found that phosphorylation of P by PLK1 is enhanced by NP. The PLK1 binding site in MuV P was mapped to residues 146 to 148 within the S(pS/T)P motif, and the phosphorylation site was identified as residues S292 and S294.IMPORTANCEIt has previously been shown that P acts as a chaperone for NP, which encapsidates viral genomic RNA to form the NP-RNA complex, the functional template for viral RNA synthesis. Thus, it is assumed that phosphorylation of P may regulate NP's ability to form the NP-RNA complex, thereby regulating viral RNA synthesis. Our work demonstrates that MuV NP affects phosphorylation of P, suggesting that NP can regulate viral RNA synthesis by regulating phosphorylation of P.

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Journal articles on the topic 'Polo kinases'

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