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Protein & Peptide Letters


ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

Research Article

Elucidation of PLK1 Linked Biomarkers in Oesophageal Cancer Cell Lines: A Step Towards Novel Signaling Pathways by p53 and PLK1-Linked Functions Crosstalk

Author(s): Nousheen Bibi*, Ted Hupp, Mohammad Amjad Kamal and Sajid Rashid*

Volume 28, Issue 3, 2021

Published on: 01 September, 2020

Page: [340 - 358] Pages: 19

DOI: 10.2174/0929866527999200901201837

Price: $65


Background: Oesophgeal adenocarcinoma (OAC) is the most frequent cause of cancer death. POLO-like kinase 1 (PLK1) is overexpressed in broad spectrum of tumors and has prognostic value in many cancers including esophageal cancer, suggesting its potential as a therapeutic target. p53, the guardian of genome is the most important tumor suppressors that represses the promoter of PLK1, whereas tumor cells with inactive p53 are arrested in mitosis due to DNA damage. PLK1 expression has been linked to the elevated p53 expression and has been shown to act as a biomarker that predicts poor prognosis in OAC.

Objectives: The aim of the present study was identification of PLK1 associated phosphorylation targets in p53 mutant and p53 normal cells to explore the downstream signaling evets.

Methods: Here we develop a proof-of-concept phospho-proteomics approach to identify possible biomarkers that can be used to identify mutant p53 or wild-type p53 pathways. We treated PLK1 asynchronously followed by mass spectrometry data analysis. Protein networking and motif analysis tools were used to identify the significant clusters and potential biomarkers.

Results: We investigated approximately 1300 potential PLK1-dependent phosphopeptides by LCMS/ MS. In total, 2216 and 1155 high confidence phosphosites were identified in CP-A (p53+) and OE33 (p53-) cell lines owing to PLK1 inhibition. Further clustering and motif assessment uncovered many significant biomarkers with known and novel link to PLK1.

Conclusion: Taken together, our study suggests that PLK1 may serve as a potential therapeutic target in human OAC. The data highlight the efficacy and specificity of small molecule PLK1 kinase inhibitors to identify novel signaling pathways in vivo.

Keywords: Oesophageal adenocarcinoma, PLK1, p53 signaling, phosphopeptides, cancer death, biomarkers.

Graphical Abstract
Strebhardt, K. Multifaceted polo-like kinases: drug targets and antitargets for cancer therapy. Nat. Rev. Drug Discov., 2010, 9(8), 643-660.
[] [PMID: 20671765]
Archambault, V.; Glover, D.M. Polo-like kinases: conservation and divergence in their functions and regulation. Nat. Rev. Mol. Cell Biol., 2009, 10(4), 265-275.
[] [PMID: 19305416]
Petronczki, M.; Lénárt, P.; Peters, J.M. Polo on the rise-from mitotic entry to cytokinesis with plk1. Dev. Cell, 2008, 14(5), 646-659.
[] [PMID: 18477449]
Golsteyn, R.M.; Schultz, S.J.; Bartek, J.; Ziemiecki, A.; Ried, T.; Nigg, E.A. Cell cycle analysis and chromosomal localization of human Plk1, a putative homologue of the mitotic kinases Drosophila polo and Saccharomyces cerevisiae Cdc5. J. Cell Sci., 1994, 107(Pt 6), 1509-1517.
[PMID: 7962193]
Lee, K.S.; Yuan, Y.L.; Kuriyama, R.; Erikson, R.L. Plk is an M-phase-specific protein kinase and interacts with a kinesin-like protein, CHO1/MKLP-1. Mol. Cell. Biol., 1995, 15(12), 7143-7151.
[] [PMID: 8524282]
Arnaud, L.; Pines, J.; Nigg, E.A. GFP tagging reveals human Polo-like kinase 1 at the kinetochore/centromere region of mitotic chromosomes. Chromosoma, 1998, 107(6-7), 424-429.
[] [PMID: 9914374]
Barr, F.A.; Silljé, H.H.; Nigg, E.A. Polo-like kinases and the orchestration of cell division. Nat. Rev. Mol. Cell Biol., 2004, 5(6), 429-440.
[] [PMID: 15173822]
Strebhardt, K.; Ullrich, A. Targeting polo-like kinase 1 for cancer therapy. Nat. Rev. Cancer, 2006, 6(4), 321-330.
[] [PMID: 16557283]
Schmucker, S. Sumara, I. Molecular dynamics of PLK1 during mitosis. Mol. Cell. Oncology 2014, 1(2), e954507.
Smith, M.R.; Wilson, M.L.; Hamanaka, R.; Chase, D.; Kung, H.; Longo, D.L.; Ferris, D.K. Malignant transformation of mammalian cells initiated by constitutive expression of the polo-like kinase. Biochem. Biophys. Res. Commun., 1997, 234(2), 397-405.
[] [PMID: 9177283]
Eckerdt, F.; Yuan, J.; Strebhardt, K. Polo-like kinases and oncogenesis. Oncogene, 2005, 24(2), 267-276.
[] [PMID: 15640842]
Takahashi, T.; Sano, B.; Nagata, T.; Kato, H.; Sugiyama, Y.; Kunieda, K.; Kimura, M.; Okano, Y.; Saji, S. Polo-like kinase 1 (PLK1) is overexpressed in primary colorectal cancers. Cancer Sci., 2003, 94(2), 148-152.
[] [PMID: 12708489]
Wolf, G.; Hildenbrand, R.; Schwar, C.; Grobholz, R.; Kaufmann, M.; Stutte, H.J.; Strebhardt, K.; Bleyl, U. Polo-like kinase: a novel marker of proliferation: correlation with estrogen-receptor expression in human breast cancer. Pathol. Res. Pract., 2000, 196(11), 753-759.
[] [PMID: 11186170]
Tokumitsu, Y.; Mori, M.; Tanaka, S.; Akazawa, K.; Nakano, S.; Niho, Y. Prognostic significance of polo-like kinase expression in esophageal carcinoma. Int. J. Oncol., 1999, 15(4), 687-692.
[] [PMID: 10493949]
Gray, P.J.Jr.; Bearss, D.J.; Han, H.; Nagle, R.; Tsao, M.S.; Dean, N.; Von Hoff, D.D. Identification of human polo-like kinase 1 as a potential therapeutic target in pancreatic cancer. Mol. Cancer Ther., 2004, 3(5), 641-646.
[PMID: 15141022]
Knecht, R.; Elez, R.; Oechler, M.; Solbach, C.; von Ilberg, C.; Strebhardt, K. Prognostic significance of polo-like kinase (PLK) expression in squamous cell carcinomas of the head and neck. Cancer Res., 1999, 59(12), 2794-2797.
[PMID: 10383133]
Takai, N.; Miyazaki, T.; Fujisawa, K.; Nasu, K.; Hamanaka, R.; Miyakawa, I. Expression of polo-like kinase in ovarian cancer is associated with histological grade and clinical stage. Cancer Lett., 2001, 164(1), 41-49.
[] [PMID: 11166914]
Sato, F.; Abraham, J.M.; Yin, J.; Kan, T.; Ito, T.; Mori, Y.; Hamilton, J.P.; Jin, Z.; Cheng, Y.; Paun, B.; Berki, A.T.; Wang, S.; Shimada, Y.; Meltzer, S.J. Polo-like kinase and survivin are esophageal tumor-specific promoters. Biochem. Biophys. Res. Commun., 2006, 342(2), 465-471.
[] [PMID: 16487489]
Dibb, M.; Han, N.; Choudhury, J.; Hayes, S.; Valentine, H.; West, C.; Ang, Y.S.; Sharrocks, A.D. The FOXM1-PLK1 axis is commonly upregulated in oesophageal adenocarcinoma. Br. J. Cancer, 2012, 107(10), 1766-1775.
[] [PMID: 23037713]
Hu, K.; Law, J.H.; Fotovati, A.; Dunn, S.E. Small interfering RNA library screen identified polo-like kinase-1 (PLK1) as a potential therapeutic target for breast cancer that uniquely eliminates tumor-initiating cells. Breast Cancer Res., 2012, 14(1), R22.
[] [PMID: 22309939]
Francescangeli, F.; Patrizii, M.; Signore, M.; Federici, G.; Di Franco, S.; Pagliuca, A.; Baiocchi, M.; Biffoni, M.; Ricci Vitiani, L.; Todaro, M.; De Maria, R.; Zeuner, A. Proliferation state and polo-like kinase1 dependence of tumorigenic colon cancer cells. Stem Cells, 2012, 30(9), 1819-1830.
[] [PMID: 22753241]
Harris, P.S.; Venkataraman, S.; Alimova, I.; Birks, D.K.; Donson, A.M.; Knipstein, J.; Dubuc, A.; Taylor, M.D.; Handler, M.H.; Foreman, N.K.; Vibhakar, R. Polo-like kinase 1 (PLK1) inhibition suppresses cell growth and enhances radiation sensitivity in medulloblastoma cells. BMC Cancer, 2012, 12, 80.
[] [PMID: 22390279]
Lee, C.; Fotovati, A.; Triscott, J. Chen, J, Venugopal, C, Singhal, A, Dunham, C, Kerr, J,M, Verreault, M, Yip, S, Wakimoto, H, Jones, C, Jayanthan, A, Narendran, A, Singh, S.K, Dunn, S.E. POLO-like kinase 1 inhibition kills glioblastomamultiforme brain tumor cells in part through loss of SOX2 and delays tumor progression in mice. Stem Cells, 2012, 30, 1064-1075.
[] [PMID: 22415968]
Grinshtein, N.; Datti, A.; Fujitani, M.; Uehling, D.; Prakesch, M.; Isaac, M.; Irwin, M.S.; Wrana, J.L.; Al-Awar, R.; Kaplan, D.R. Small molecule kinase inhibitor screen identifies polo-like kinase 1 as a target for neuroblastoma tumor-initiating cells. Cancer Res., 2011, 71(4), 1385-1395.
[] [PMID: 21303981]
Elia, A.E.; Cantley, L.C.; Yaffe, M.B. Proteomic screen finds pSer/pThr-binding domain localizing Plk1 to mitotic substrates. Science, 2003, 299(5610), 1228-1231.
[] [PMID: 12595692]
Yap, T.A.; Molife, L.R.; Blagden, S.P.; de Bono, S. Targeting cell cycle kinases and kinesins in anticancer drug development. Expert Opin. Drug Discov., 2007, 2(4), 539-560.
[] [PMID: 23484760]
Lens, S.M.; Voest, E.E.; Medema, R.H. Shared and separate functions of polo-like kinases and aurora kinases in cancer. Nat. Rev. Cancer, 2010, 10(12), 825-841.
[] [PMID: 21102634]
Taylor, S.; Peters, J.M. Polo and Aurora kinases: lessons derived from chemical biology. Curr. Opin. Cell Biol., 2008, 20(1), 77-84.
[] [PMID: 18249108]
Keppner, S.; Proschak, E.; Kaufmann, M.; Strebhardt, K.; Schneider, G.; Spänkuch, B. Biological impact of freezing Plk1 in its inactive conformation in cancer cells. Cell Cycle, 2010, 9(4), 761-773.
[] [PMID: 20139717]
Gutteridge, R.E.A. Plk1 Inhibitors in Cancer Therapy: From Laboratory to Clinics. Mol. Cancer Ther., 2016, 15(7), 1427-35.
Vose, J.M.; Friedberg, J.W.; Waller, E.K.; Cheson, B.D.; Juvvigunta, V.; Fritsch, H.; Petit, C.; Munzert, G.; Younes, A. The PLK1 inhibitor BI 2536 in patients with refractory or relapsed non-Hodgkin’s lymphoma: A Phase I, open-label, single dose-escalation study. Leuk. Lymphoma, 2013, 54(4), 708-713.
Jimeno, A.; Li, J.; Messersmith, W.A.; Laheru, D.; Rudek, M.A.; Maniar, M.; Hidalgo, M.; Baker, S.D.; Donehower, R.C. Phase I study of ON 01910.Na, a novel modulator of the Polo-like kinase 1 pathway, in adult patients with solid tumors. J. Clin. Oncol., 2008, 26(34), 5504-5510.
[] [PMID: 18955447]
Mross, K.; Dittrich, C.; Aulitzky, W.E.; Strumberg, D.; Schutte, J.; Schmid, R.M.; Hollerbach, S.; Merger, M.; Munzert, G.; Fleischer, F.; Scheulen, M.E. A randomised phase II trial of the Polo-like kinase inhibitor BI 2536 in chemo-naïve patients with unresectable exocrine adenocarcinoma of the pancreas - a study within the Central European Society Anticancer Drug Research (CESAR) collaborative network. Br. J. Cancer, 2012, 107(2), 280-286.
[] [PMID: 22699824]
Mross, K.; Frost, A.; Steinbild, S.; Hedbom, S.; Rentschler, J.; Kaiser, R.; Rouyrre, N.; Trommeshauser, D.; Hoesl, C.E.; Munzert, G. Phase I dose escalation and pharmacokinetic study of BI 2536, a novel Polo-like kinase 1 inhibitor, in patients with advanced solid tumors. J. Clin. Oncol., 2008, 26(34), 5511-5517.
[] [PMID: 18955456]
Schöffski, P.; Awada, A.; Dumez, H.; Gil, T.; Bartholomeus, S.; Wolter, P.; Taton, M.; Fritsch, H.; Glomb, P.; Munzert, G. A phase I, dose-escalation study of the novel Polo-like kinase inhibitor volasertib (BI 6727) in patients with advanced solid tumours. Eur. J. Cancer, 2012, 48(2), 179-186.
[] [PMID: 22119200]
Olmos, D.; Barker, D.; Sharma, R.; Brunetto, A.T.; Yap, T.A.; Taegtmeyer, A.B.; Barriuso, J.; Medani, H.; Degenhardt, Y.Y.; Allred, A.J.; Smith, D.A.; Murray, S.C.; Lampkin, T.A.; Dar, M.M.; Wilson, R.; de Bono, J.S.; Blagden, S.P. Phase I study of GSK461364, a specific and competitive Polo-like kinase 1 inhibitor, in patients with advanced solid malignancies. Clin. Cancer Res., 2011, 17(10), 3420-3430.
[] [PMID: 21459796]
Garland, L.L.; Taylor, C.; Pilkington, D.L.; Cohen, J.L.; Von Hoff, D.D. A phase I pharmacokinetic study of HMN-214, a novel oral stilbene derivative with polo-like kinase-1-interacting properties, in patients with advanced solid tumors. Clin. Cancer Res., 2006, 12(17), 5182-5189.
[] [PMID: 16951237]
Levine, A.J. The evolution of the p53 family of genes. Cell Cycle, 2012, 11(2), 214-215.
[] [PMID: 22214668]
Maddocks, O.D.; Berkers, C.R.; Mason, S.M.; Zheng, L.; Blyth, K.; Gottlieb, E.; Vousden, K.H. Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells. Nature, 2013, 493(7433), 542-546.
[] [PMID: 23242140]
Vousden, K.H.; Prives, C. Blinded by the Light: the growing complexity of p53. Cell, 2009, 137(3), 413-431.
[] [PMID: 19410540]
Hong, H.; Takahashi, K.; Ichisaka, T.; Aoi, T.; Kanagawa, O.; Nakagawa, M.; Okita, K.; Yamanaka, S. Suppression of induced pluripotent stem cell generation by the p53-p21 pathway. Nature, 2009, 460(7259), 1132-1135.
[] [PMID: 19668191]
Kawamura, T.; Suzuki, J.; Wang, Y.V.; Menendez, S.; Morera, L.B.; Raya, A.; Wahl, G.M.; Izpisúa Belmonte, J.C. Linking the p53 tumour suppressor pathway to somatic cell reprogramming. Nature, 2009, 460(7259), 1140-1144.
[] [PMID: 19668186]
Li, H.; Collado, M.; Villasante, A.; Strati, K.; Ortega, S.; Cañamero, M.; Blasco, M.A.; Serrano, M. The Ink4/Arf locus is a barrier for iPS cell reprogramming. Nature, 2009, 460(7259), 1136-1139.
[] [PMID: 19668188]
Marión, R.M.; Strati, K.; Li, H.; Murga, M.; Blanco, R.; Ortega, S.; Fernandez-Capetillo, O.; Serrano, M.; Blasco, M.A.A.A. p53-mediated DNA damage response limits reprogramming to ensure iPS cell genomic integrity. Nature, 2009, 460(7259), 1149-1153.
[] [PMID: 19668189]
Utikal, J. Immortalization eliminates a roadblock during cellular reprogramming into iPS cells. Nature, 2009, 460(7259), 1145-1148.
Frezza, C.; Martins, C.P. From tumor prevention to therapy: empowering p53 to fight back. Drug Resist. Updat., 2012, 15(5-6), 258-267.
[] [PMID: 23164556]
Jiang, P.; Du, W.; Wang, X.; Mancuso, A.; Gao, X.; Wu, M.; Yang, X. p53 regulates biosynthesis through direct inactivation of glucose-6-phosphate dehydrogenase. Nat. Cell Biol., 2011, 13(3), 310-316.
[] [PMID: 21336310]
Baker, S.J.; Fearon, E.R.; Nigro, J.M.; Hamilton, S.R.; Preisinger, A.C.; Jessup, J.M.; vanTuinen, P.; Ledbetter, D.H.; Barker, D.F.; Nakamura, Y.; White, R.; Vogelstein, B. Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. Science, 1989, 244(4901), 217-221.
[] [PMID: 2649981]
Junttila, M.R.; Evan, G.I. p53--a Jack of all trades but master of none. Nat. Rev. Cancer, 2009, 9(11), 821-829.
[] [PMID: 19776747]
Bode, A.M.; Dong, Z. Post-translational modification of p53 in tumorigenesis. Nat. Rev. Cancer, 2004, 4(10), 793-805.
[] [PMID: 15510160]
Riley, T.; Sontag, E.; Chen, P.; Levine, A. Transcriptional control of human p53-regulated genes. Nat. Rev. Mol. Cell Biol., 2008, 9(5), 402-412.
[] [PMID: 18431400]
McKenzie, L.; King, S.; Marcar, L.; Nicol, S.; Dias, S.S.; Schumm, K.; Robertson, P.; Bourdon, J.C.; Perkins, N.; Fuller-Pace, F.; Meek, D.W. p53-dependent repression of polo-like kinase-1 (PLK1). Cell Cycle, 2010, 9(20), 4200-4212.
[] [PMID: 20962589]
Zhu, H.; Chang, B.D.; Uchiumi, T.; Roninson, I.B. Identification of promoter elements responsible for transcriptional inhibition of polo-like kinase 1 and topoisomerase IIalpha genes by p21(WAF1/CIP1/SDI1). Cell Cycle, 2002, 1(1), 59-66.
[] [PMID: 12429910]
Sur, S.; Pagliarini, R.; Bunz, F.; Rago, C.; Diaz, L.A., Jr; Kinzler, K.W.; Vogelstein, B.; Papadopoulos, N. A panel of isogenic human cancer cells suggests a therapeutic approach for cancers with inactivated p53. Proc. Natl. Acad. Sci. USA, 2009, 106(10), 3964-3969.
[] [PMID: 19225112]
Tanaka, H.; Shibagaki, I.; Shimada, Y.; Wagata, T.; Imamura, M.; Ishizaki, K. Characterization of p53 gene mutations in esophageal squamous cell carcinoma cell lines: increased frequency and different spectrum of mutations from primary tumors. Int. J. Cancer, 1996, 65(3), 372-376.
[<372:AID-IJC16>3.0.CO;2-C] [PMID: 8575860]
Boonstra, J.J.; van Marion, R.; Beer, D.G.; Lin, L.; Chaves, P.; Ribeiro, C.; Pereira, A.D.; Roque, L.; Darnton, S.J.; Altorki, N.K.; Schrump, D.S.; Klimstra, D.S.; Tang, L.H.; Eshleman, J.R.; Alvarez, H.; Shimada, Y.; van Dekken, H.; Tilanus, H.W.; Dinjens, W.N. Verification and unmasking of widely used human esophageal adenocarcinoma cell lines. J. Natl. Cancer Inst., 2010, 102(4), 271-274.
[] [PMID: 20075370]
Nakajima, H.; Toyoshima-Morimoto, F.; Taniguchi, E.; Nishida, E. Identification of a consensus motif for Plk (Polo-like kinase) phosphorylation reveals Myt1 as a Plk1 substrate. J. Biol. Chem., 2003, 278(28), 25277-25280.
[] [PMID: 12738781]
Bibi, N.; Parveen, Z.; Rashid, S. Identification of potential Plk1 targets in a cell-cycle specific proteome through structural dynamics of kinase and Polo box-mediated interactions. PLoS One, 2013, 8(8), e70843.
[] [PMID: 23967120]
Sharan, R.; Ulitsky, I.; Shamir, R. Network-based prediction of protein function. Mol. Syst. Biol., 2007, 3, 88.
[] [PMID: 17353930]
Milenković, T.; Przulj, N. Uncovering biological network function via graphlet degree signatures. Cancer Inform., 2008, 6, 257-273.
[] [PMID: 19259413]
Ma, H.T.; Tsang, Y.H.; Marxer, M.; Poon, R.Y.C. Cyclin A2-cyclin-dependent kinase 2 cooperates with the PLK1-SCFbeta-TrCP1-EMI1-anaphase-promoting complex/ cyclosome axis to promote genome reduplication in the absence of mitosis. Mol. Cell. Biol., 2009, 29(24), 6500-6514.
[] [PMID: 19822658]
Wu, S.Y.; McNae, I.; Kontopidis, G.; McClue, S.J.; McInnes, C.; Stewart, K.J.; Wang, S.; Zheleva, D.I.; Marriage, H.; Lane, D.P.; Taylor, P.; Fischer, P.M.; Walkinshaw, M.D. Discovery of a novel family of CDK inhibitors with the program LIDAEUS: structural basis for ligand-induced disordering of the activation loop. Structure, 2003, 11(4), 399-410.
[] [PMID: 12679018]
Morris, G.M.; Huey, R.; Lindstrom, W.; Sanner, M.F.; Belew, R.K.; Goodsell, D.S.; Olson, A.J. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J. Comput. Chem., 2009, 30(16), 2785-2791.
[] [PMID: 19399780]
Torchala, M.; Moal, I.H.; Chaleil, R.A.; Fernandez-Recio, J.; Bates, P.A. SwarmDock: a server for flexible protein-protein docking. Bioinformatics, 2013, 29(6), 807-809.
[] [PMID: 23343604]
Wallace, A.C.; Laskowski, R.A.; Thornton, J.M. LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions. Protein Eng., 1995, 8(2), 127-134.
[] [PMID: 7630882]
Beausoleil, S.A.; Villén, J.; Gerber, S.A.; Rush, J.; Gygi, S.P. A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nat. Biotechnol., 2006, 24(10), 1285-1292.
[] [PMID: 16964243]
Neumayer, G.; Belzil, C.; Gruss, O.J.; Nguyen, M.D. TPX2: of spindle assembly, DNA damage response, and cancer. Cell. Mol. Life Sci., 2014, 71(16), 3027-3047.
[] [PMID: 24556998]
Dovey, M.; Patton, E.E.; Bowman, T.; North, T.; Goessling, W.; Zhou, Y.; Zon, L.I. Topoisomerase II alpha is required for embryonic development and liver regeneration in zebrafish. Mol. Cell. Biol., 2009, 29(13), 3746-3753.
[] [PMID: 19380487]
De Luca, M.; Lavia, P.; Guarguaglini, G. A functional interplay between Aurora-A, Plk1 and TPX2 at spindle poles: Plk1 controls centrosomal localization of Aurora-A and TPX2 spindle association. Cell Cycle, 2006, 5(3), 296-303.
[] [PMID: 16418575]
Song, B.; Liu, X.S.; Liu, X. Polo-like kinase 1 (Plk1): an Unexpected Player in DNA Replication. Cell Div., 2012, 7, 3.
[] [PMID: 22309699]
Raab, M.; Krämer, A.; Hehlgans, S.; Sanhaji, M.; Kurunci-Csacsko, E.; Dötsch, C.; Bug, G.; Ottmann, O.; Becker, S.; Pachl, F.; Kuster, B.; Strebhardt, K. Mitotic arrest and slippage induced by pharmacological inhibition of Polo-like kinase 1. Mol. Oncol., 2015, 9(1), 140-154.
[] [PMID: 25169932]
Willems, E.; Dedobbeleer, M.; Digregorio, M.; Lombard, A.; Lumapat, P.N.; Rogister, B. The functional diversity of Aurora kinases: a comprehensive review. Cell Div., 2018, 13, 7.
[] [PMID: 30250494]
Castro, A.; Arlot-Bonnemains, Y.; Vigneron, S.; Labbé, J.C.; Prigent, C.; Lorca, T. APC/Fizzy-Related targets Aurora-A kinase for proteolysis. EMBO Rep., 2002, 3(5), 457-462.
[] [PMID: 11964384]
Zimniak, T.; Fitz, V.; Zhou, H.; Lampert, F.; Opravil, S.; Mechtler, K.; Stolt-Bergner, P.; Westermann, S. Spatiotemporal regulation of Ipl1/Aurora activity by direct Cdk1 phosphorylation. Curr. Biol., 2012, 22(9), 787-793.
[] [PMID: 22521784]
Bibi, N.; Rashid, S.; Nicholson, J.; Malloy, M.; O’Neill, R.; Blake, D.; Hupp, T. An Integrative “Omics” Approach, for identification of bona fides PLK1 associated biomarker in esophageal adenocarcinoma. Curr. Cancer Drug Targets, 2019, 19(9), 742-755.
[] [PMID: 30747067]
Lowery, D.M.; Clauser, K.R.; Hjerrild, M.; Lim, D.; Alexander, J.; Kishi, K.; Ong, S.E.; Gammeltoft, S.; Carr, S.A.; Yaffe, M.B. Proteomic screen defines the Polo-box domain interactome and identifies Rock2 as a Plk1 substrate. EMBO J, 2007, 26(9), 2262-2273.
[] [PMID: 17446864]

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