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Polo-like kinase

About: Polo-like kinase is a research topic. Over the lifetime, 1697 publications have been published within this topic receiving 149752 citations.


Papers
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Journal ArticleDOI
Erich A. Nigg1
TL;DR: A better understanding of the cell cycle machinery and its deregulation during oncogenesis may provide novel opportunities for the diagnostic and therapeutic management of cancer and other proliferation‐related diseases.
Abstract: Passage through the cell cycle requires the successive activation of different cyclin-dependent protein kinases (CDKs). These enzymes are controlled by transient associations with cyclin regulatory subunits, binding of inhibitory polypeptides and reversible phosphorylation reactions. To promote progression towards DNA replication, CDK/cyclin complexes phosphorylate proteins required for the activation of genes involved in DNA synthesis, as well as components of the DNA replication machinery. Subsequently, a different set of CDK/cyclin complexes triggers the phosphorylation of numerous proteins to promote the profound structural reorganizations that accompany the entry of cells into mitosis. At present, much research is focused on elucidating the links between CDK/cyclin complexes and signal transduction pathways controlling cell growth, differentiation and death. In future, a better understanding of the cell cycle machinery and its deregulation during oncogenesis may provide novel opportunities for the diagnostic and therapeutic management of cancer and other proliferation-related diseases.

956 citations

Journal ArticleDOI
TL;DR: Ten human protein kinases based on their structural relation to p34cdc2 are identified, opening the possibility of combinatorial regulation of the cell cycle together with the emerging large family of cyclins.
Abstract: The p34cdc2 protein kinase is known to regulate important transitions in the eukaryotic cell cycle. We have identified 10 human protein kinases based on their structural relation to p34cdc2. Seven of these kinases are novel and the products of five share greater than 50% amino acid sequence identity with p34cdc2. The seven novel genes are broadly expressed in human cell lines and tissues with each displaying some cell type or tissue specificity. The cdk3 gene, like cdc2 and cdk2, can complement cdc28 mutants of Saccharomyces cerevisiae, suggesting that all three of these protein kinases can play roles in the regulation of the mammalian cell cycle. The identification of a large family of cdc2-related kinases opens the possibility of combinatorial regulation of the cell cycle together with the emerging large family of cyclins.

930 citations

Journal ArticleDOI
TL;DR: The structural features of the kinase domain and the unique polo-box domain ofPLK1 that are most suited for drug development are addressed and the current understanding of the therapeutic potential of PLK1 is discussed.
Abstract: Human polo-like kinase 1 (PLK1) is essential during mitosis and in the maintenance of genomic stability. PLK1 is overexpressed in human tumours and has prognostic potential in cancer, indicating its involvement in carcinogenesis and its potential as a therapeutic target. The use of different PLK1 inhibitors has increased our knowledge of mitotic regulation and allowed us to assess their ability to suppress tumour growth in vivo. We address the structural features of the kinase domain and the unique polo-box domain of PLK1 that are most suited for drug development and discuss our current understanding of the therapeutic potential of PLK1.

799 citations

Journal ArticleDOI
TL;DR: A potent small-molecule inhibitor of mammalian Plk1, BI 2536, is reported, which inhibits PlK1 enzyme activity at low nanomolar concentrations and causes a mitotic arrest and induces apoptosis in human cancer cell lines of diverse tissue origin and oncogenome signature.

786 citations

Journal ArticleDOI
TL;DR: This work shows that the Cdc14 phosphatase triggers mitotic exit by three parallel mechanisms, each of which inhibits Cdk activity, and induces degradation of mitotic cyclins.

780 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
2023111
202277
202119
202015
201923
201823