Serine/threonine-protein kinase PLK1

Details

Name
Serine/threonine-protein kinase PLK1
Kind
protein
Synonyms
  • 2.7.11.21
  • PLK
  • PLK-1
  • Polo-like kinase 1
  • Serine/threonine-protein kinase 13
  • STPK13
Gene Name
PLK1
UniProtKB Entry
P53350Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0019464|Serine/threonine-protein kinase PLK1
MSAAVTAGKLARAPADPGKAGVPGVAAPGAPAAAPPAKEIPEVLVDPRSRRRYVRGRFLG
KGGFAKCFEISDADTKEVFAGKIVPKSLLLKPHQREKMSMEISIHRSLAHQHVVGFHGFF
EDNDFVFVVLELCRRRSLLELHKRRKALTEPEARYYLRQIVLGCQYLHRNRVIHRDLKLG
NLFLNEDLEVKIGDFGLATKVEYDGERKKTLCGTPNYIAPEVLSKKGHSFEVDVWSIGCI
MYTLLVGKPPFETSCLKETYLRIKKNEYSIPKHINPVAASLIQKMLQTDPTARPTINELL
NDEFFTSGYIPARLPITCLTIPPRFSIAPSSLDPSNRKPLTVLNKGLENPLPERPREKEE
PVVRETGEVVDCHLSDMLQQLHSVNASKPSERGLVRQEEAEDPACIPIFWVSKWVDYSDK
YGLGYQLCDNSVGVLFNDSTRLILYNDGDSLQYIERDGTESYLTVSSHPNSLMKKITLLK
YFRNYMSEHLLKAGANITPREGDELARLPYLRTWFRTRSAIILHLSNGSVQINFFQDHTK
LILCPLMAAVTYIDEKRDFRTYRLSLLEEYGCCKELASRLRYARTMVDKLLSSRSASNRL
KAS
Number of residues
603
Molecular Weight
68254.03
Theoretical pI
9.19
GO Classification
Functions
anaphase-promoting complex binding / ATP binding / microtubule binding / protein kinase activity / protein kinase binding / protein serine/threonine kinase activity
Processes
establishment of protein localization / female meiosis chromosome segregation / G2/M transition of mitotic cell cycle / homologous chromosome segregation / metaphase/anaphase transition of mitotic cell cycle / microtubule bundle formation / mitotic cell cycle / mitotic cytokinesis / mitotic sister chromatid segregation / negative regulation of apoptotic process / negative regulation of cyclin-dependent protein serine/threonine kinase activity / peptidyl-serine phosphorylation / positive regulation of peptidyl-threonine phosphorylation / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / positive regulation of proteolysis / positive regulation of ubiquitin-protein transferase activity / protein destabilization / protein localization to chromatin / protein phosphorylation / protein ubiquitination / regulation of cell cycle / regulation of mitotic cell cycle / regulation of mitotic metaphase/anaphase transition / regulation of mitotic spindle assembly / regulation of protein binding / synaptonemal complex disassembly
Components
centrosome / chromatin / cytoplasm / cytosol / kinetochore / microtubule cytoskeleton / midbody / nucleoplasm / nucleus / spindle / spindle midzone / spindle pole / synaptonemal complex
General Function
Serine/threonine-protein kinase that performs several important functions throughout M phase of the cell cycle, including the regulation of centrosome maturation and spindle assembly, the removal of cohesins from chromosome arms, the inactivation of anaphase-promoting complex/cyclosome (APC/C) inhibitors, and the regulation of mitotic exit and cytokinesis (PubMed:11202906, PubMed:12207013, PubMed:12447691, PubMed:12524548, PubMed:12738781, PubMed:12852856, PubMed:12939256, PubMed:14532005, PubMed:14734534, PubMed:15070733, PubMed:15148369, PubMed:15469984, PubMed:16198290, PubMed:16247472, PubMed:16980960, PubMed:17081991, PubMed:17351640, PubMed:17376779, PubMed:17617734, PubMed:18174154, PubMed:18331714, PubMed:18418051, PubMed:18477460, PubMed:18521620, PubMed:18615013, PubMed:19160488, PubMed:19351716, PubMed:19468300, PubMed:19468302, PubMed:19473992, PubMed:19509060, PubMed:19597481, PubMed:23455478, PubMed:23509069, PubMed:28512243, PubMed:8991084). Polo-like kinase proteins act by binding and phosphorylating proteins that are already phosphorylated on a specific motif recognized by the POLO box domains (PubMed:11202906, PubMed:12207013, PubMed:12447691, PubMed:12524548, PubMed:12738781, PubMed:12852856, PubMed:12939256, PubMed:14532005, PubMed:14734534, PubMed:15070733, PubMed:15148369, PubMed:15469984, PubMed:16198290, PubMed:16247472, PubMed:16980960, PubMed:17081991, PubMed:17351640, PubMed:17376779, PubMed:17617734, PubMed:18174154, PubMed:18331714, PubMed:18418051, PubMed:18477460, PubMed:18521620, PubMed:18615013, PubMed:19160488, PubMed:19351716, PubMed:19468300, PubMed:19468302, PubMed:19473992, PubMed:19509060, PubMed:19597481, PubMed:23455478, PubMed:23509069, PubMed:28512243, PubMed:8991084). Phosphorylates BORA, BUB1B/BUBR1, CCNB1, CDC25C, CEP55, ECT2, ERCC6L, FBXO5/EMI1, FOXM1, KIF20A/MKLP2, CENPU, NEDD1, NINL, NPM1, NUDC, PKMYT1/MYT1, KIZ, MRE11, PPP1R12A/MYPT1, POLQ, PRC1, RACGAP1/CYK4, RAD51, RHNO1, SGO1, STAG2/SA2, TEX14, TOPORS, p73/TP73, TPT1, WEE1 and HNRNPU (PubMed:11202906, PubMed:12207013, PubMed:12447691, PubMed:12524548, PubMed:12738781, PubMed:12852856, PubMed:12939256, PubMed:14532005, PubMed:14734534, PubMed:15070733, PubMed:15148369, PubMed:15469984, PubMed:16198290, PubMed:16247472, PubMed:16980960, PubMed:17081991, PubMed:17218258, PubMed:17351640, PubMed:17376779, PubMed:17617734, PubMed:18174154, PubMed:18331714, PubMed:18418051, PubMed:18477460, PubMed:18521620, PubMed:18615013, PubMed:19160488, PubMed:19351716, PubMed:19468300, PubMed:19468302, PubMed:19473992, PubMed:19509060, PubMed:19597481, PubMed:22325354, PubMed:23455478, PubMed:23509069, PubMed:25986610, PubMed:26811421, PubMed:28512243, PubMed:37440612, PubMed:37674080, PubMed:8991084). Plays a key role in centrosome functions and the assembly of bipolar spindles by phosphorylating KIZ, NEDD1 and NINL (PubMed:16980960, PubMed:19509060). NEDD1 phosphorylation promotes subsequent targeting of the gamma-tubulin ring complex (gTuRC) to the centrosome, an important step for spindle formation (PubMed:19509060). Phosphorylation of NINL component of the centrosome leads to NINL dissociation from other centrosomal proteins (PubMed:12852856). Involved in mitosis exit and cytokinesis by phosphorylating CEP55, ECT2, KIF20A/MKLP2, CENPU, PRC1 and RACGAP1 (PubMed:12939256, PubMed:16247472, PubMed:17351640, PubMed:19468300, PubMed:19468302). Recruited at the central spindle by phosphorylating and docking PRC1 and KIF20A/MKLP2; creates its own docking sites on PRC1 and KIF20A/MKLP2 by mediating phosphorylation of sites subsequently recognized by the POLO box domains (PubMed:12939256, PubMed:17351640). Phosphorylates RACGAP1, thereby creating a docking site for the Rho GTP exchange factor ECT2 that is essential for the cleavage furrow formation (PubMed:19468300, PubMed:19468302). Promotes the central spindle recruitment of ECT2 (PubMed:16247472). Plays a central role in G2/M transition of mitotic cell cycle by phosphorylating CCNB1, CDC25C, FOXM1, CENPU, PKMYT1/MYT1, PPP1R12A/MYPT1 and WEE1 (PubMed:11202906, PubMed:12447691, PubMed:12524548, PubMed:19160488). Part of a regulatory circuit that promotes the activation of CDK1 by phosphorylating the positive regulator CDC25C and inhibiting the negative regulators WEE1 and PKMYT1/MYT1 (PubMed:11202906). Also acts by mediating phosphorylation of cyclin-B1 (CCNB1) on centrosomes in prophase (PubMed:12447691, PubMed:12524548). Phosphorylates FOXM1, a key mitotic transcription regulator, leading to enhance FOXM1 transcriptional activity (PubMed:19160488). Involved in kinetochore functions and sister chromatid cohesion by phosphorylating BUB1B/BUBR1, FBXO5/EMI1 and STAG2/SA2 (PubMed:15148369, PubMed:15469984, PubMed:17376779, PubMed:18331714). PLK1 is high on non-attached kinetochores suggesting a role of PLK1 in kinetochore attachment or in spindle assembly checkpoint (SAC) regulation (PubMed:17617734). Required for kinetochore localization of BUB1B (PubMed:17376779). Regulates the dissociation of cohesin from chromosomes by phosphorylating cohesin subunits such as STAG2/SA2 (By similarity). Phosphorylates SGO1: required for spindle pole localization of isoform 3 of SGO1 and plays a role in regulating its centriole cohesion function (PubMed:18331714). Mediates phosphorylation of FBXO5/EMI1, a negative regulator of the APC/C complex during prophase, leading to FBXO5/EMI1 ubiquitination and degradation by the proteasome (PubMed:15148369, PubMed:15469984). Acts as a negative regulator of p53 family members: phosphorylates TOPORS, leading to inhibit the sumoylation of p53/TP53 and simultaneously enhance the ubiquitination and subsequent degradation of p53/TP53 (PubMed:19473992). Phosphorylates the transactivation domain of the transcription factor p73/TP73, leading to inhibit p73/TP73-mediated transcriptional activation and pro-apoptotic functions. Phosphorylates BORA, and thereby promotes the degradation of BORA (PubMed:18521620). Contributes to the regulation of AURKA function (PubMed:18615013, PubMed:18662541). Also required for recovery after DNA damage checkpoint and entry into mitosis (PubMed:18615013, PubMed:18662541). Phosphorylates MISP, leading to stabilization of cortical and astral microtubule attachments required for proper spindle positioning (PubMed:23509069). Together with MEIKIN, acts as a regulator of kinetochore function during meiosis I: required both for mono-orientation of kinetochores on sister chromosomes and protection of centromeric cohesin from separase-mediated cleavage (By similarity). Phosphorylates CEP68 and is required for its degradation (PubMed:25503564). Regulates nuclear envelope breakdown during prophase by phosphorylating DCTN1 resulting in its localization in the nuclear envelope (PubMed:20679239). Phosphorylates the heat shock transcription factor HSF1, promoting HSF1 nuclear translocation upon heat shock (PubMed:15661742). Phosphorylates HSF1 also in the early mitotic period; this phosphorylation regulates HSF1 localization to the spindle pole, the recruitment of the SCF(BTRC) ubiquitin ligase complex induicing HSF1 degradation, and hence mitotic progression (PubMed:18794143). Regulates mitotic progression by phosphorylating RIOK2 (PubMed:21880710). Through the phosphorylation of DZIP1 regulates the localization during mitosis of the BBSome, a ciliary protein complex involved in cilium biogenesis (PubMed:27979967). Regulates DNA repair during mitosis by mediating phosphorylation of POLQ and RHNO1, thereby promoting POLQ recruitment to DNA damage sites (PubMed:37440612, PubMed:37674080). Phosphorylates ATXN10 which may play a role in the regulation of cytokinesis and may stimulate the proteasome-mediated degradation of ATXN10 (PubMed:21857149)
Specific Function
anaphase-promoting complex binding
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0019465|Serine/threonine-protein kinase PLK1 (PLK1)
ATGAGTGCTGCAGTGACTGCAGGGAAGCTGGCACGGGCACCGGCCGACCCTGGGAAAGCC
GGGGTCCCCGGAGTTGCAGCTCCCGGAGCTCCGGCGGCGGCTCCACCGGCGAAAGAGATC
CCGGAGGTCCTAGTGGACCCACGCAGCCGGCGGCGCTATGTGCGGGGCCGCTTTTTGGGC
AAGGGCGGCTTTGCCAAGTGCTTCGAGATCTCGGACGCGGACACCAAGGAGGTGTTCGCG
GGCAAGATTGTGCCTAAGTCTCTGCTGCTCAAGCCGCACCAGAGGGAGAAGATGTCCATG
GAAATATCCATTCACCGCAGCCTCGCCCACCAGCACGTCGTAGGATTCCACGGCTTTTTC
GAGGACAACGACTTCGTGTTCGTGGTGTTGGAGCTCTGCCGCCGGAGGTCTCTCCTGGAG
CTGCACAAGAGGAGGAAAGCCCTGACTGAGCCTGAGGCCCGATACTACCTACGGCAAATT
GTGCTTGGCTGCCAGTACCTGCACCGAAACCGAGTTATTCATCGAGACCTCAAGCTGGGC
AACCTTTTCCTGAATGAAGATCTGGAGGTGAAAATAGGGGATTTTGGACTGGCAACCAAA
GTCGAATATGACGGGGAGAGGAAGAAGACCCTGTGTGGGACTCCTAATTACATAGCTCCC
GAGGTGCTGAGCAAGAAAGGGCACAGTTTCGAGGTGGATGTGTGGTCCATTGGGTGTATC
ATGTATACCTTGTTAGTGGGCAAACCACCTTTTGAGACTTCTTGCCTAAAAGAGACCTAC
CTCCGGATCAAGAAGAATGAATACAGTATTCCCAAGCACATCAACCCCGTGGCCGCCTCC
CTCATCCAGAAGATGCTTCAGACAGATCCCACTGCCCGCCCAACCATTAACGAGCTGCTT
AATGACGAGTTCTTTACTTCTGGCTATATCCCTGCCCGTCTCCCCATCACCTGCCTGACC
ATTCCACCAAGGTTTTCGATTGCTCCCAGCAGCCTGGACCCCAGCAACCGGAAGCCCCTC
ACAGTCCTCAATAAAGGCTTGGAGAACCCCCTGCCTGAGCGTCCCCGGGAAAAAGAAGAA
CCAGTGGTTCGAGAGACAGGTGAGGTGGTCGACTGCCACCTCAGTGACATGCTGCAGCAG
CTGCACAGTGTCAATGCCTCCAAGCCCTCGGAGCGTGGGCTGGTCAGGCAAGAGGAGGCT
GAGGATCCTGCCTGCATCCCCATCTTCTGGGTCAGCAAGTGGGTGGACTATTCGGACAAG
TACGGCCTTGGGTATCAGCTCTGTGATAACAGCGTGGGGGTGCTCTTCAATGACTCAACA
CGCCTCATCCTCTACAATGATGGTGACAGCCTGCAGTACATAGAGCGTGACGGCACTGAG
TCCTACCTCACCGTGAGTTCCCATCCCAACTCCTTGATGAAGAAGATCACCCTCCTTAAA
TATTTCCGCAATTACATGAGCGAGCACTTGCTGAAGGCAGGTGCCAACATCACGCCGCGC
GAAGGTGATGAGCTCGCCCGGCTGCCCTACCTACGGACCTGGTTCCGCACCCGCAGCGCC
ATCATCCTGCACCTCAGCAACGGCAGCGTGCAGATCAACTTCTTCCAGGATCACACCAAG
CTCATCTTGTGCCCACTGATGGCAGCCGTGACCTACATCGACGAGAAGCGGGACTTCCGC
ACATACCGCCTGAGTCTCCTGGAGGAGTACGGCTGCTGCAAGGAGCTGGCCAGCCGGCTC
CGCTACGCCCGCACTATGGTGGACAAGCTGCTGAGCTCACGCTCGGCCAGCAACCGTCTC
AAGGCCTCCTAA
Chromosome Location
16
Locus
16p12.2
External Identifiers
ResourceLink
UniProtKB IDP53350
UniProtKB Entry NamePLK1_HUMAN
GenBank Protein ID393017
GenBank Gene IDU01038
GeneCard IDPLK1
HGNC IDHGNC:9077
PDB ID(s)1Q4K, 1Q4O, 1UMW, 2OGQ, 2OJX, 2OU7, 2OWB, 2RKU, 2V5Q, 2YAC, 3BZI, 3C5L, 3FC2, 3FVH, 3HIH, 3HIK, 3KB7, 3P2W, 3P2Z, 3P34, 3P35, 3P36, 3P37, 3Q1I, 3RQ7, 3THB, 4A4L, 4A4O, 4DFW, 4E67, 4E9C, 4E9D, 4H5X, 4H71, 4HAB, 4HCO, 4HY2, 4J52, 4J53, 4LKL, 4LKM, 4O56, 4O6W, 4O9W, 4RCP, 4WHH, 4WHK, 4WHL, 4X9R, 4X9V, 4X9W, 5J19, 5NEI, 5NFU, 5NJE, 5NMM, 5NN1, 5NN2, 5TA6, 5TA8, 6AX4, 6GY2, 7MSO, 7MX1, 8BJT, 8CRC, 8JOQ, 8JOY, 8X72, 8XB9
KEGG IDhsa:5347
IUPHAR/Guide To Pharmacology ID2168
NCBI Gene ID5347
General References
  1. Hamanaka R, Maloid S, Smith MR, O'Connell CD, Longo DL, Ferris DK: Cloning and characterization of human and murine homologues of the Drosophila polo serine-threonine kinase. Cell Growth Differ. 1994 Mar;5(3):249-57. [Article]
  2. Lake RJ, Jelinek WR: Cell cycle- and terminal differentiation-associated regulation of the mouse mRNA encoding a conserved mitotic protein kinase. Mol Cell Biol. 1993 Dec;13(12):7793-801. [Article]
  3. Golsteyn RM, Schultz SJ, Bartek J, Ziemiecki A, Ried T, Nigg EA: 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 Jun;107 ( Pt 6):1509-17. [Article]
  4. Holtrich U, Wolf G, Brauninger A, Karn T, Bohme B, Rubsamen-Waigmann H, Strebhardt K: Induction and down-regulation of PLK, a human serine/threonine kinase expressed in proliferating cells and tumors. Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1736-40. [Article]
  5. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  6. Brauninger A, Strebhardt K, Rubsamen-Waigmann H: Identification and functional characterization of the human and murine polo-like kinase (Plk) promoter. Oncogene. 1995 Nov 2;11(9):1793-800. [Article]
  7. Uchiumi T, Longo DL, Ferris DK: Cell cycle regulation of the human polo-like kinase (PLK) promoter. J Biol Chem. 1997 Apr 4;272(14):9166-74. [Article]
  8. Lane HA, Nigg EA: Antibody microinjection reveals an essential role for human polo-like kinase 1 (Plk1) in the functional maturation of mitotic centrosomes. J Cell Biol. 1996 Dec;135(6 Pt 2):1701-13. [Article]
  9. Roshak AK, Capper EA, Imburgia C, Fornwald J, Scott G, Marshall LA: The human polo-like kinase, PLK, regulates cdc2/cyclin B through phosphorylation and activation of the cdc25C phosphatase. Cell Signal. 2000 Jun;12(6):405-11. [Article]
  10. Jang YJ, Ma S, Terada Y, Erikson RL: Phosphorylation of threonine 210 and the role of serine 137 in the regulation of mammalian polo-like kinase. J Biol Chem. 2002 Nov 15;277(46):44115-20. Epub 2002 Aug 30. [Article]
  11. Yuan J, Eckerdt F, Bereiter-Hahn J, Kurunci-Csacsko E, Kaufmann M, Strebhardt K: Cooperative phosphorylation including the activity of polo-like kinase 1 regulates the subcellular localization of cyclin B1. Oncogene. 2002 Nov 28;21(54):8282-92. [Article]
  12. Wind M, Kelm O, Nigg EA, Lehmann WD: Identification of phosphorylation sites in the polo-like kinases Plx1 and Plk1 by a novel strategy based on element and electrospray high resolution mass spectrometry. Proteomics. 2002 Nov;2(11):1516-23. [Article]
  13. Casenghi M, Meraldi P, Weinhart U, Duncan PI, Korner R, Nigg EA: Polo-like kinase 1 regulates Nlp, a centrosome protein involved in microtubule nucleation. Dev Cell. 2003 Jul;5(1):113-25. [Article]
  14. Walter SA, Cutler RE Jr, Martinez R, Gishizky M, Hill RJ: Stk10, a new member of the polo-like kinase kinase family highly expressed in hematopoietic tissue. J Biol Chem. 2003 May 16;278(20):18221-8. Epub 2003 Mar 13. [Article]
  15. 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 Jul 11;278(28):25277-80. Epub 2003 May 8. [Article]
  16. Neef R, Preisinger C, Sutcliffe J, Kopajtich R, Nigg EA, Mayer TU, Barr FA: Phosphorylation of mitotic kinesin-like protein 2 by polo-like kinase 1 is required for cytokinesis. J Cell Biol. 2003 Sep 1;162(5):863-75. Epub 2003 Aug 25. [Article]
  17. Jackman M, Lindon C, Nigg EA, Pines J: Active cyclin B1-Cdk1 first appears on centrosomes in prophase. Nat Cell Biol. 2003 Feb;5(2):143-8. [Article]
  18. Lindon C, Pines J: Ordered proteolysis in anaphase inactivates Plk1 to contribute to proper mitotic exit in human cells. J Cell Biol. 2004 Jan 19;164(2):233-41. [Article]
  19. Hansen DV, Loktev AV, Ban KH, Jackson PK: Plk1 regulates activation of the anaphase promoting complex by phosphorylating and triggering SCFbetaTrCP-dependent destruction of the APC Inhibitor Emi1. Mol Biol Cell. 2004 Dec;15(12):5623-34. Epub 2004 Oct 6. [Article]
  20. Watanabe N, Arai H, Nishihara Y, Taniguchi M, Watanabe N, Hunter T, Osada H: M-phase kinases induce phospho-dependent ubiquitination of somatic Wee1 by SCFbeta-TrCP. Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4419-24. Epub 2004 Mar 22. [Article]
  21. Moshe Y, Boulaire J, Pagano M, Hershko A: Role of Polo-like kinase in the degradation of early mitotic inhibitor 1, a regulator of the anaphase promoting complex/cyclosome. Proc Natl Acad Sci U S A. 2004 May 25;101(21):7937-42. Epub 2004 May 17. [Article]
  22. Fabbro M, Zhou BB, Takahashi M, Sarcevic B, Lal P, Graham ME, Gabrielli BG, Robinson PJ, Nigg EA, Ono Y, Khanna KK: Cdk1/Erk2- and Plk1-dependent phosphorylation of a centrosome protein, Cep55, is required for its recruitment to midbody and cytokinesis. Dev Cell. 2005 Oct;9(4):477-88. [Article]
  23. Guarguaglini G, Duncan PI, Stierhof YD, Holmstrom T, Duensing S, Nigg EA: The forkhead-associated domain protein Cep170 interacts with Polo-like kinase 1 and serves as a marker for mature centrioles. Mol Biol Cell. 2005 Mar;16(3):1095-107. Epub 2004 Dec 22. [Article]
  24. Eldridge AG, Loktev AV, Hansen DV, Verschuren EW, Reimann JD, Jackson PK: The evi5 oncogene regulates cyclin accumulation by stabilizing the anaphase-promoting complex inhibitor emi1. Cell. 2006 Jan 27;124(2):367-80. [Article]
  25. Qi W, Tang Z, Yu H: Phosphorylation- and polo-box-dependent binding of Plk1 to Bub1 is required for the kinetochore localization of Plk1. Mol Biol Cell. 2006 Aug;17(8):3705-16. Epub 2006 Jun 7. [Article]
  26. Oshimori N, Ohsugi M, Yamamoto T: The Plk1 target Kizuna stabilizes mitotic centrosomes to ensure spindle bipolarity. Nat Cell Biol. 2006 Oct;8(10):1095-101. Epub 2006 Sep 17. [Article]
  27. Niiya F, Tatsumoto T, Lee KS, Miki T: Phosphorylation of the cytokinesis regulator ECT2 at G2/M phase stimulates association of the mitotic kinase Plk1 and accumulation of GTP-bound RhoA. Oncogene. 2006 Feb 9;25(6):827-37. [Article]
  28. Kang YH, Park JE, Yu LR, Soung NK, Yun SM, Bang JK, Seong YS, Yu H, Garfield S, Veenstra TD, Lee KS: Self-regulated Plk1 recruitment to kinetochores by the Plk1-PBIP1 interaction is critical for proper chromosome segregation. Mol Cell. 2006 Nov 3;24(3):409-22. [Article]
  29. Kanaji S, Saito H, Tsujitani S, Matsumoto S, Tatebe S, Kondo A, Ozaki M, Ito H, Ikeguchi M: Expression of polo-like kinase 1 (PLK1) protein predicts the survival of patients with gastric carcinoma. Oncology. 2006;70(2):126-33. Epub 2006 Apr 26. [Article]
  30. Salvatore G, Nappi TC, Salerno P, Jiang Y, Garbi C, Ugolini C, Miccoli P, Basolo F, Castellone MD, Cirafici AM, Melillo RM, Fusco A, Bittner ML, Santoro M: A cell proliferation and chromosomal instability signature in anaplastic thyroid carcinoma. Cancer Res. 2007 Nov 1;67(21):10148-58. [Article]
  31. Baumann C, Korner R, Hofmann K, Nigg EA: PICH, a centromere-associated SNF2 family ATPase, is regulated by Plk1 and required for the spindle checkpoint. Cell. 2007 Jan 12;128(1):101-14. [Article]
  32. Pouwels J, Kukkonen AM, Lan W, Daum JR, Gorbsky GJ, Stukenberg T, Kallio MJ: Shugoshin 1 plays a central role in kinetochore assembly and is required for kinetochore targeting of Plk1. Cell Cycle. 2007 Jul 1;6(13):1579-85. Epub 2007 May 16. [Article]
  33. Zhang Y, Tian Y, Chen Q, Chen D, Zhai Z, Shu HB: TTDN1 is a Plk1-interacting protein involved in maintenance of cell cycle integrity. Cell Mol Life Sci. 2007 Mar;64(5):632-40. [Article]
  34. Matsumura S, Toyoshima F, Nishida E: Polo-like kinase 1 facilitates chromosome alignment during prometaphase through BubR1. J Biol Chem. 2007 May 18;282(20):15217-27. Epub 2007 Mar 21. [Article]
  35. Liu L, Zhang M, Zou P: Expression of PLK1 and survivin in diffuse large B-cell lymphoma. Leuk Lymphoma. 2007 Nov;48(11):2179-83. [Article]
  36. Neef R, Gruneberg U, Kopajtich R, Li X, Nigg EA, Sillje H, Barr FA: Choice of Plk1 docking partners during mitosis and cytokinesis is controlled by the activation state of Cdk1. Nat Cell Biol. 2007 Apr;9(4):436-44. Epub 2007 Mar 11. [Article]
  37. Stegmeier F, Sowa ME, Nalepa G, Gygi SP, Harper JW, Elledge SJ: The tumor suppressor CYLD regulates entry into mitosis. Proc Natl Acad Sci U S A. 2007 May 22;104(21):8869-74. Epub 2007 May 10. [Article]
  38. Bassermann F, Frescas D, Guardavaccaro D, Busino L, Peschiaroli A, Pagano M: The Cdc14B-Cdh1-Plk1 axis controls the G2 DNA-damage-response checkpoint. Cell. 2008 Jul 25;134(2):256-67. doi: 10.1016/j.cell.2008.05.043. [Article]
  39. Pohl C, Jentsch S: Final stages of cytokinesis and midbody ring formation are controlled by BRUCE. Cell. 2008 Mar 7;132(5):832-45. doi: 10.1016/j.cell.2008.01.012. [Article]
  40. Soond SM, Barry SP, Melino G, Knight RA, Latchman DS, Stephanou A: p73-mediated transcriptional activity is negatively regulated by polo-like kinase 1. Cell Cycle. 2008 May 1;7(9):1214-23. Epub 2008 Feb 15. [Article]
  41. Chan EH, Santamaria A, Sillje HH, Nigg EA: Plk1 regulates mitotic Aurora A function through betaTrCP-dependent degradation of hBora. Chromosoma. 2008 Oct;117(5):457-69. doi: 10.1007/s00412-008-0165-5. Epub 2008 Jun 3. [Article]
  42. Wang X, Yang Y, Duan Q, Jiang N, Huang Y, Darzynkiewicz Z, Dai W: sSgo1, a major splice variant of Sgo1, functions in centriole cohesion where it is regulated by Plk1. Dev Cell. 2008 Mar;14(3):331-41. doi: 10.1016/j.devcel.2007.12.007. [Article]
  43. Yamashiro S, Yamakita Y, Totsukawa G, Goto H, Kaibuchi K, Ito M, Hartshorne DJ, Matsumura F: Myosin phosphatase-targeting subunit 1 regulates mitosis by antagonizing polo-like kinase 1. Dev Cell. 2008 May;14(5):787-97. doi: 10.1016/j.devcel.2008.02.013. [Article]
  44. Koida N, Ozaki T, Yamamoto H, Ono S, Koda T, Ando K, Okoshi R, Kamijo T, Omura K, Nakagawara A: Inhibitory role of Plk1 in the regulation of p73-dependent apoptosis through physical interaction and phosphorylation. J Biol Chem. 2008 Mar 28;283(13):8555-63. doi: 10.1074/jbc.M710608200. Epub 2008 Jan 3. [Article]
  45. Zhu H, Coppinger JA, Jang CY, Yates JR 3rd, Fang G: FAM29A promotes microtubule amplification via recruitment of the NEDD1-gamma-tubulin complex to the mitotic spindle. J Cell Biol. 2008 Dec 1;183(5):835-48. doi: 10.1083/jcb.200807046. Epub 2008 Nov 24. [Article]
  46. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [Article]
  47. Fu Z, Malureanu L, Huang J, Wang W, Li H, van Deursen JM, Tindall DJ, Chen J: Plk1-dependent phosphorylation of FoxM1 regulates a transcriptional programme required for mitotic progression. Nat Cell Biol. 2008 Sep;10(9):1076-82. doi: 10.1038/ncb1767. [Article]
  48. Macurek L, Lindqvist A, Lim D, Lampson MA, Klompmaker R, Freire R, Clouin C, Taylor SS, Yaffe MB, Medema RH: Polo-like kinase-1 is activated by aurora A to promote checkpoint recovery. Nature. 2008 Sep 4;455(7209):119-23. doi: 10.1038/nature07185. Epub 2008 Jul 9. [Article]
  49. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [Article]
  50. Svendsen JM, Smogorzewska A, Sowa ME, O'Connell BC, Gygi SP, Elledge SJ, Harper JW: Mammalian BTBD12/SLX4 assembles a Holliday junction resolvase and is required for DNA repair. Cell. 2009 Jul 10;138(1):63-77. doi: 10.1016/j.cell.2009.06.030. [Article]
  51. Yang X, Li H, Zhou Z, Wang WH, Deng A, Andrisani O, Liu X: Plk1-mediated phosphorylation of Topors regulates p53 stability. J Biol Chem. 2009 Jul 10;284(28):18588-92. doi: 10.1074/jbc.C109.001560. Epub 2009 May 27. [Article]
  52. Zhang X, Chen Q, Feng J, Hou J, Yang F, Liu J, Jiang Q, Zhang C: Sequential phosphorylation of Nedd1 by Cdk1 and Plk1 is required for targeting of the gammaTuRC to the centrosome. J Cell Sci. 2009 Jul 1;122(Pt 13):2240-51. doi: 10.1242/jcs.042747. Epub 2009 Jun 9. [Article]
  53. Jang CY, Coppinger JA, Seki A, Yates JR 3rd, Fang G: Plk1 and Aurora A regulate the depolymerase activity and the cellular localization of Kif2a. J Cell Sci. 2009 May 1;122(Pt 9):1334-41. doi: 10.1242/jcs.044321. Epub 2009 Apr 7. [Article]
  54. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. [Article]
  55. Wolfe BA, Takaki T, Petronczki M, Glotzer M: Polo-like kinase 1 directs assembly of the HsCyk-4 RhoGAP/Ect2 RhoGEF complex to initiate cleavage furrow formation. PLoS Biol. 2009 May 5;7(5):e1000110. doi: 10.1371/journal.pbio.1000110. Epub 2009 May 26. [Article]
  56. Burkard ME, Maciejowski J, Rodriguez-Bravo V, Repka M, Lowery DM, Clauser KR, Zhang C, Shokat KM, Carr SA, Yaffe MB, Jallepalli PV: Plk1 self-organization and priming phosphorylation of HsCYK-4 at the spindle midzone regulate the onset of division in human cells. PLoS Biol. 2009 May 5;7(5):e1000111. doi: 10.1371/journal.pbio.1000111. Epub 2009 May 26. [Article]
  57. Strebhardt K: Multifaceted polo-like kinases: drug targets and antitargets for cancer therapy. Nat Rev Drug Discov. 2010 Aug;9(8):643-60. doi: 10.1038/nrd3184. [Article]
  58. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. [Article]
  59. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  60. Dunsch AK, Linnane E, Barr FA, Gruneberg U: The astrin-kinastrin/SKAP complex localizes to microtubule plus ends and facilitates chromosome alignment. J Cell Biol. 2011 Mar 21;192(6):959-68. doi: 10.1083/jcb.201008023. Epub 2011 Mar 14. [Article]
  61. Ikeda M, Chiba S, Ohashi K, Mizuno K: Furry protein promotes aurora A-mediated Polo-like kinase 1 activation. J Biol Chem. 2012 Aug 10;287(33):27670-81. doi: 10.1074/jbc.M112.378968. Epub 2012 Jun 29. [Article]
  62. Van Damme P, Lasa M, Polevoda B, Gazquez C, Elosegui-Artola A, Kim DS, De Juan-Pardo E, Demeyer K, Hole K, Larrea E, Timmerman E, Prieto J, Arnesen T, Sherman F, Gevaert K, Aldabe R: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12449-54. doi: 10.1073/pnas.1210303109. Epub 2012 Jul 18. [Article]
  63. Yeh TY, Kowalska AK, Scipioni BR, Cheong FK, Zheng M, Derewenda U, Derewenda ZS, Schroer TA: Dynactin helps target Polo-like kinase 1 to kinetochores via its left-handed beta-helical p27 subunit. EMBO J. 2013 Apr 3;32(7):1023-35. doi: 10.1038/emboj.2013.30. Epub 2013 Mar 1. [Article]
  64. Zhu M, Settele F, Kotak S, Sanchez-Pulido L, Ehret L, Ponting CP, Gonczy P, Hoffmann I: MISP is a novel Plk1 substrate required for proper spindle orientation and mitotic progression. J Cell Biol. 2013 Mar 18;200(6):773-87. doi: 10.1083/jcb.201207050. [Article]
  65. Beck J, Maerki S, Posch M, Metzger T, Persaud A, Scheel H, Hofmann K, Rotin D, Pedrioli P, Swedlow JR, Peter M, Sumara I: Ubiquitylation-dependent localization of PLK1 in mitosis. Nat Cell Biol. 2013 Apr;15(4):430-9. doi: 10.1038/ncb2695. Epub 2013 Mar 3. [Article]
  66. Pagan JK, Marzio A, Jones MJ, Saraf A, Jallepalli PV, Florens L, Washburn MP, Pagano M: Degradation of Cep68 and PCNT cleavage mediate Cep215 removal from the PCM to allow centriole separation, disengagement and licensing. Nat Cell Biol. 2015 Jan;17(1):31-43. doi: 10.1038/ncb3076. Epub 2014 Dec 15. [Article]
  67. Elia AE, Rellos P, Haire LF, Chao JW, Ivins FJ, Hoepker K, Mohammad D, Cantley LC, Smerdon SJ, Yaffe MB: The molecular basis for phosphodependent substrate targeting and regulation of Plks by the Polo-box domain. Cell. 2003 Oct 3;115(1):83-95. [Article]
  68. Cheng KY, Lowe ED, Sinclair J, Nigg EA, Johnson LN: The crystal structure of the human polo-like kinase-1 polo box domain and its phospho-peptide complex. EMBO J. 2003 Nov 3;22(21):5757-68. [Article]
  69. Kothe M, Kohls D, Low S, Coli R, Cheng AC, Jacques SL, Johnson TL, Lewis C, Loh C, Nonomiya J, Sheils AL, Verdries KA, Wynn TA, Kuhn C, Ding YH: Structure of the catalytic domain of human polo-like kinase 1. Biochemistry. 2007 May 22;46(20):5960-71. Epub 2007 Apr 27. [Article]
  70. Kothe M, Kohls D, Low S, Coli R, Rennie GR, Feru F, Kuhn C, Ding YH: Selectivity-determining residues in Plk1. Chem Biol Drug Des. 2007 Dec;70(6):540-6. Epub 2007 Nov 13. [Article]
  71. Garcia-Alvarez B, de Carcer G, Ibanez S, Bragado-Nilsson E, Montoya G: Molecular and structural basis of polo-like kinase 1 substrate recognition: Implications in centrosomal localization. Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3107-12. Epub 2007 Feb 16. [Article]
  72. Bandeiras TM, Hillig RC, Matias PM, Eberspaecher U, Fanghanel J, Thomaz M, Miranda S, Crusius K, Putter V, Amstutz P, Gulotti-Georgieva M, Binz HK, Holz C, Schmitz AA, Lang C, Donner P, Egner U, Carrondo MA, Muller-Tiemann B: Structure of wild-type Plk-1 kinase domain in complex with a selective DARPin. Acta Crystallogr D Biol Crystallogr. 2008 Apr;64(Pt 4):339-53. doi: 10.1107/S0907444907068217. Epub 2008 Mar 19. [Article]
  73. Yun SM, Moulaei T, Lim D, Bang JK, Park JE, Shenoy SR, Liu F, Kang YH, Liao C, Soung NK, Lee S, Yoon DY, Lim Y, Lee DH, Otaka A, Appella E, McMahon JB, Nicklaus MC, Burke TR Jr, Yaffe MB, Wlodawer A, Lee KS: Structural and functional analyses of minimal phosphopeptides targeting the polo-box domain of polo-like kinase 1. Nat Struct Mol Biol. 2009 Aug;16(8):876-82. doi: 10.1038/nsmb.1628. Epub 2009 Jul 13. [Article]
  74. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. [Article]

Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
3-[3-chloro-5-(5-{[(1S)-1-phenylethyl]amino}isoxazolo[5,4-c]pyridin-3-yl)phenyl]propan-1-olexperimentalunknowntargetDetails
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4-(4-METHYLPIPERAZIN-1-YL)-N-[5-(2-THIENYLACETYL)-1,5-DIHYDROPYRROLO[3,4-C]PYRAZOL-3-YL]BENZAMIDEexperimentalunknowntargetDetails
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Fostamatinibapproved, investigationalunknowntargetinhibitorDetails
VolasertibinvestigationalunknowntargetinhibitorDetails
MK-1496investigationalyestargetinhibitorDetails
OnvansertibinvestigationalyestargetinhibitorDetails
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