Atlas of Genetics and Cytogenetics in Oncology and Haematology
PLK1 (polo-like kinase 1 (Drosophila))
| Identity |
| Other names | PLK |
| STPK13 (SERINE/THREONINE PROTEIN KINASE 13) | |
| Hugo | PLK1 |
| Location | 16p12.1 |
| Local_order | Genes flanking PLK1 in centromere to telomere direction on 16p12 are: |
| Note | Polo like kinases belong to serine/threonine kinases that are conserved from yeast to human cells. Polo like kinases exhibit important roles in key cellular events regulating cell cycle progression and cell division such as centrosome maturation, cdc2 activation, mitotic spindle formation, regulation of the anaphase promoting complex, chromosome segregation, cytokinesis, DNA damage response pathways and apoptosis. |
| DNA/RNA |
 | |
| The alignment of PLK1 mRNA (NM_005030) to its genomic sequence NC_000016). | |
| Description | PLK1 mRNA spans approximately 11.5 kb and has 10 exons. The sizes of the exons 1 to 10 are 461, 169, 145, 94, 220, 156, 78, 155, 183 and 508 bps. |
| Transcription | PLK1 mRNA (NM_005030) is 2204 bp. PLK1 expression is believed to reach its peak value in mitosis in the cell cycle. It is highly expressed in actively proliferating tissues such as those in the placenta, spleen, ovary, and testis. High expression of PLK1 is also detected in various neoplastic tissues. Northern blot analysis reveals low or undetectable levels of PLK1 transcript in most other adult tissues (e.g.: brain, thymus, liver, lung, pancreas, heart, kidney, stomach, intestine and skin). |
| Pseudogene | Mouse Plk gene maps to Chromosome 7 and the processed pseudogene to mouse Chromosome 5. No human pseudogene for PLK1 has been reported. |
| Protein |
| Description | Protein consists of 603 amino acids and is 66kDa. In addition to the N-terminus kinase domain, there are two conserved polo-box regions of 30 amino acids at the C-terminus. Kinase activity is regulated at least in part, by the polo-boxes that are functionally important for both auto-inhibition and sub-cellular localization. |
| Expression | PLK1 protein becomes a target of the anaphase-promoting complex/cyclosome and is degraded by the ubiquitin-proteasome pathway as cells exit mitosis. |
| Localisation | During interphase, PLK1 localizes to centrosomes. In early mitosis, it associates with mitotic spindle poles. A recombinant GFP-PLK1 protein localizes to centromere/kinetochore region, suggesting a possible role for chromosome separation. |
| Function | PLK1 is believed to be involved in the regulation of key steps during cell division, DNA damage repair pathways, apoptosis, and the progression of the cell cycle. PLK1 has roles in the activation of cdc2 through cdc25 and direct phosphorylation of cyclin B1, through which MPF (mitosis promoting factor) is activated so that mitosis can start. Microinjection of PLK1 antibodies causes failure of g-tubulin recruitment to the centrosomes. This failure results in immature centrosomes and monopolar spindle formation. Similar microinjection experiments in cell lines (transformed HeLa and non-immortalized Hs68 fibroblasts) result in a marked inhibition of cell cycle progression. PLK1 also has a possible role during cytokinesis based on the observation that PLK1 interacts and co-localizes with a kinesin related motor protein (CHO1/MKLP-1) at the interzone during anaphase and the mid-body during telophase and cytokinesis. Evidence suggests that BRCA2 is a substrate of PLK1 both in response to DNA damage and during normal cell cycle progression. This suggests a role for PLK1 in regulating DNA damage repair. Other studies have shown that the loss of PLK1 expression can induce pro-apoptotic pathways and inhibit growth. Based on yeast and murine studies of meiosis, human PLK1 may also have a regulatory function in meiosis. S. cerevisiae polo kinase CDC5 is required to phosphorylate and remove meiotic cohesion during the first cell division. In CDC5 depleted cells, kinetochores are bioriented during meiosis I, and Mam1, a protein essential for coorientation, fails to associate with kinetochores. CDC5 is believed to have roles in sister-kinetochore coorientation and chromosome segregation during meiosis I.. |
| Homology | P.troglodytes: PLK1, polo-like kinase, XP_510879.1, 735 aa M.musculus: Plk1, polo-like kinase 1 (Drosophila), NP_035251.2, 603 aa R.norvegicus: Plk1, polo-like kinase 1 (Drosophila), NP_058796.1, 603 aa D.melanogaster: polo, polo, NP_524179.2, 576 aa C.elegans: plk-1 PoLo Kinase, NP_741243.1, 649 aa S.cerevisiae: CDC5, NP_013714.1, 705 aa |
| Implicated in |
| Note | Increased PLK1 levels are detected in a variety of cancers. |
| Disease | Increased PLK1 transcript has been detected in a variety of tumor types including esophageal, head and neck squamous cell, liver, lung and breast carcinomas. Immunohistochemical studies also demonstrate increased PLK1 protein levels in melanomas, breast, ovarian, prostate cancers, and head, neck squamous cell carcinomas. |
| Prognosis | Statistically significant correlations between increased PLK1 expression and decreased patient survival suggest that PLK1 is a negative prognostic indicator for some types of cancer. For example, |
| Oncogenesis | Oncogenic properties of PLK1 are believed to be due to its role in driving cell cycle progression. Supporting evidence comes from the overexpression studies of PLK1 in NIH3T3 cell line. These cells become capable of forming foci and growing in soft agar and more importantly, these cells can form tumors in nude mice due to PLK1 overexpression. PLK1 has also been linked to known pathways that are altered during the neoplastic transformation. Retinoblastoma tumor suppressor (RB) pathway activation results in the repression of PLK1 promoter in a SWI/SNF chromatin remodeling complex dependent manner. In case of RB inactivation, PLK1 expression seems to be deregulated. This new finding suggests that PLK1 may be a target of the retinoblastoma tumor suppressor (RB) pathway. Moreover, PLK1 seems to be involved in the tumor suppressor p53 related pathways. Evidence suggests that PLK1 can inhibit transactivation and pro-apoptotic functions of p53 function by physical interaction and phosphorylation. In addition to PLK1šs role in normal cell cycle regulation, its connection to such known tumor suppressors may be crucial for the tumorigenesis processes. |
| To be noted |
| A study also suggests that PLK1 protein cannot be detected in normal brain tissue but it can be detected in brain tissues from Alzheimeršs disease patients. |
| External links |
| Bibliography |
| Cell cycle- and terminal differentiation-associated regulation of the mouse mRNA encoding a conserved mitotic protein kinase. |
| Lake RJ, Jelinek WR |
| Molecular and cellular biology. 1993 ; 13 (12) : 7793-7801. |
| PMID 7902533 |
| Cell cycle analysis and chromosomal localization of human Plk1, a putative homologue of the mitotic kinases Drosophila polo and Saccharomyces cerevisiae Cdc5. |
| Golsteyn RM, Schultz SJ, Bartek J, Ziemiecki A, Ried T, Nigg EA |
| Journal of cell science. 1994 ; 107 ( Pt 6) : 1509-1517. |
| PMID 7962193 |
| Cloning and characterization of human and murine homologues of the Drosophila polo serine-threonine kinase. |
| Hamanaka R, Maloid S, Smith MR, O'Connell CD, Longo DL, Ferris DK |
| Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research. 1994 ; 5 (3) : 249-257. |
| PMID 8018557 |
| Plk is an M-phase-specific protein kinase and interacts with a kinesin-like protein, CHO1/MKLP-1. |
| Lee KS, Yuan YL, Kuriyama R, Erikson RL |
| Molecular and cellular biology. 1995 ; 15 (12) : 7143-7151. |
| PMID 8524282 |
| Antibody microinjection reveals an essential role for human polo-like kinase 1 (Plk1) in the functional maturation of mitotic centrosomes. |
| Lane HA, Nigg EA |
| The Journal of cell biology. 1996 ; 135 (6 Pt 2) : 1701-1713. |
| PMID 8991084 |
| The mouse Plk gene: structural characterization, chromosomal localization and identification of a processed Plk pseudogene. |
| Clay FJ, Ernst MR, Trueman JW, Flegg R, Dunn AR |
| Gene. 1997 ; 198 (1-2) : 329-339. |
| PMID 9370299 |
| Malignant transformation of mammalian cells initiated by constitutive expression of the polo-like kinase. |
| Smith MR, Wilson ML, Hamanaka R, Chase D, Kung H, Longo DL, Ferris DK |
| Biochemical and biophysical research communications. 1997 ; 234 (2) : 397-405. |
| PMID 9177283 |
| GFP tagging reveals human Polo-like kinase 1 at the kinetochore/centromere region of mitotic chromosomes. |
| Arnaud L, Pines J, Nigg EA |
| Chromosoma. 1998 ; 107 (6-7) : 424-429. |
| PMID 9914374 |
| Polo-like kinases: a team that plays throughout mitosis. |
| Glover DM, Hagan IM, Tavares AA |
| Genes & development. 1998 ; 12 (24) : 3777-3787. |
| PMID 9869630 |
| Neuronal polo-like kinase in Alzheimer disease indicates cell cycle changes. |
| Harris PL, Zhu X, Pamies C, Rottkamp CA, Ghanbari HA, McShea A, Feng Y, Ferris DK, Smith MA |
| Neurobiology of aging. 2000 ; 21 (6) : 837-841. |
| PMID 11124427 |
| Polo-like kinase: a novel marker of proliferation: correlation with estrogen-receptor expression in human breast cancer. |
| Wolf G, Hildenbrand R, Schwar C, Grobholz R, Kaufmann M, Stutte HJ, Strebhardt K, Bleyl U |
| Pathology, research and practice. 2000 ; 196 (11) : 753-759. |
| PMID 11186170 |
| Expression of polo-like kinase (PLK1) in thin melanomas: a novel marker of metastatic disease. |
| Kneisel L, Strebhardt K, Bernd A, Wolter M, Binder A, Kaufmann R |
| Journal of cutaneous pathology. 2002 ; 29 (6) : 354-358. |
| PMID 12135466 |
| Role of Polo-like kinase CDC5 in programming meiosis I chromosome segregation. |
| Lee BH, Amon A |
| Science (New York, N.Y.). 2003 ; 300 (5618) : 482-486. |
| PMID 12663816 |
| M phase-specific phosphorylation of BRCA2 by Polo-like kinase 1 correlates with the dissociation of the BRCA2-P/CAF complex. |
| Lin HR, Ting NS, Qin J, Lee WH |
| The Journal of biological chemistry. 2003 ; 278 (38) : 35979-35987. |
| PMID 12815053 |
| Polo-like kinase (Plk)1 depletion induces apoptosis in cancer cells. |
| Liu X, Erikson RL |
| Proceedings of the National Academy of Sciences of the United States of America. 2003 ; 100 (10) : 5789-5794. |
| PMID 12732729 |
| Polo-like kinase 1 (PLK1) is overexpressed in primary colorectal cancers. |
| Takahashi T, Sano B, Nagata T, Kato H, Sugiyama Y, Kunieda K, Kimura M, Okano Y, Saji S |
| Cancer science. 2003 ; 94 (2) : 148-152. |
| PMID 12708489 |
| Polo-like kinase 1 and Chk2 interact and co-localize to centrosomes and the midbody. |
| Tsvetkov L, Xu X, Li J, Stern DF |
| The Journal of biological chemistry. 2003 ; 278 (10) : 8468-8475. |
| PMID 12493754 |
| Polo-like kinase 1 (Plk1) inhibits p53 function by physical interaction and phosphorylation. |
| Ando K, Ozaki T, Yamamoto H, Furuya K, Hosoda M, Hayashi S, Fukuzawa M, Nakagawara A |
| The Journal of biological chemistry. 2004 ; 279 (24) : 25549-25561. |
| PMID 15024021 |
| Hierarchical requirement of SWI/SNF in retinoblastoma tumor suppressor-mediated repression of Plk1. |
| Gunawardena RW, Siddiqui H, Solomon DA, Mayhew CN, Held J, Angus SP, Knudsen ES |
| The Journal of biological chemistry. 2004 ; 279 (28) : 29278-29285. |
| PMID 15105433 |
| Plk1 regulates activation of the anaphase promoting complex by phosphorylating and triggering SCFbetaTrCP-dependent destruction of the APC Inhibitor Emi1. |
| Hansen DV, Loktev AV, Ban KH, Jackson PK |
| Molecular biology of the cell. 2004 ; 15 (12) : 5623-5634. |
| PMID 15469984 |
| Phosphorylation of BRCA2 by the Polo-like kinase Plk1 is regulated by DNA damage and mitotic progression. |
| Lee M, Daniels MJ, Venkitaraman AR |
| Oncogene. 2004 ; 23 (4) : 865-872. |
| PMID 14647413 |
| Ordered proteolysis in anaphase inactivates Plk1 to contribute to proper mitotic exit in human cells. |
| Lindon C, Pines J |
| The Journal of cell biology. 2004 ; 164 (2) : 233-241. |
| PMID 14734534 |
| Molecular interactions of Polo-like-kinase 1 with the mitotic kinesin-like protein CHO1/MKLP-1. |
| Liu X, Zhou T, Kuriyama R, Erikson RL |
| Journal of cell science. 2004 ; 117 (Pt 15) : 3233-3246. |
| PMID 15199097 |
| Polo-like kinase isoform expression is a prognostic factor in ovarian carcinoma. |
| Weichert W, Denkert C, Schmidt M, Gekeler V, Wolf G, Kbel M, Dietel M, Hauptmann S |
| British journal of cancer. 2004 ; 90 (4) : 815-821. |
| PMID 14970859 |
| Polo-like kinase 1 is overexpressed in prostate cancer and linked to higher tumor grades. |
| Weichert W, Schmidt M, Gekeler V, Denkert C, Stephan C, Jung K, Loening S, Dietel M, Kristiansen G |
| The Prostate. 2004 ; 60 (3) : 240-245. |
| PMID 15176053 |
| Expression profiling and differential screening between hepatoblastomas and the corresponding normal livers: identification of high expression of the PLK1 oncogene as a poor-prognostic indicator of hepatoblastomas. |
| Yamada S, Ohira M, Horie H, Ando K, Takayasu H, Suzuki Y, Sugano S, Hirata T, Goto T, Matsunaga T, Hiyama E, Hayashi Y, Ando H, Suita S, Kaneko M, Sasaki F, Hashizume K, Ohnuma N, Nakagawara A |
| Oncogene. 2004 ; 23 (35) : 5901-5911. |
| PMID 15221005 |
| Polo-like kinases and oncogenesis. |
| Eckerdt F, Yuan J, Strebhardt K |
| Oncogene. 2005 ; 24 (2) : 267-276. |
| PMID 15640842 |
| Expression of Polo-Like Kinase (PLK1) in non-Hodgkin's lymphomas. |
| Mito K, Kashima K, Kikuchi H, Daa T, Nakayama I, Yokoyama S |
| Leukemia & lymphoma. 2005 ; 46 (2) : 225-231. |
| PMID 15621805 |
| Polo-like kinases (Plks) and cancer. |
| Takai N, Hamanaka R, Yoshimatsu J, Miyakawa I |
| Oncogene. 2005 ; 24 (2) : 287-291. |
| PMID 15640844 |
| Differential regulation of polo-like kinase 1, 2, 3, and 4 gene expression in mammalian cells and tissues. |
| Winkles JA, Alberts GF |
| Oncogene. 2005 ; 24 (2) : 260-266. |
| PMID 15640841 |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| Contributor(s) |
| Written | 04-2005 | Ayse Elif Erson, Elizabeth M. Petty |
| Citation |
| This paper should be referenced as such : |
| Erson AE, Petty EM . PLK1 (polo-like kinase 1 (Drosophila)). Atlas Genet Cytogenet Oncol Haematol. April 2005 . URL : http://AtlasGeneticsOncology.org/Genes/PLK1ID41747ch16p12.html |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Mon Jul 14 17:48:33 2008 |
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