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Antitubulin Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
The Polo-Like Kinases (PLKs) are a family of conserved serine/threonine kinases that are important regulators of the cell cycle through G2 and some phases of mitosis, including mitotic entry and exit, and cytokinesis. The “Polo” domain is named after the original protein encoded by the Polo gene of Drosophila melanogaster. These proteins are involved in the formation of, and modifications to, the mitotic spindle, and in the activation of CDK/Cyclin complexes during the M phase of the cell cycle. The PLKs are characterized by an amino terminal catalytic domain, and a carboxy terminal noncatalytic domain consisting of three blocks of conserved sequences known as Polo boxes which form one single functional domain. Mammalian PLKs include PLK1 (also known as STPK13), PLK2 (also known as SNK), PLK3 (also known as CNK, FNK, and PRK), PLK4 (also known as SAK or STK18), and PLK5. In particular, PLK1 acts in concert with Cyclin-dependent kinase 1 (Cyclin B1) and the Aurora kinases to orchestrate a wide range of critical cell-cycle events.
Improved Management of Autism Spectrum Disorder (ASD) by Micronutrients
Published in Kedar N. Prasad, Micronutrients in Health and Disease, 2019
In the lymphoblast cell lines from monozygotic twins with ASD, the expression of two microRNAs has-miR-29b and has-miR-219-5p that target inhibitor of DNA binding protein 3 (ID3) and polio-like kinase2 (PLK2), respectively, were altered.46
Inhibitors of the PLK1 polo-box domain: drug design strategies and therapeutic opportunities in cancer
Published in Expert Opinion on Drug Discovery, 2023
Jessy M. Stafford, Michael D. Wyatt, Campbell McInnes
In addition to the N-terminal ATP binding catalytic domain, PLKs contain a unique C terminal structure involved in Ser-pSer/pThr binding, called the Polo box domain (PBD), comprising one or two polo boxes (~100 amino acids each) connected by a flexible linker [14] (see Figure 1). PLKs1-3 exhibit a high level of sequence homology and perhaps recognize similar sequence motifs on their targets [15]. Their PBDs contain two polo boxes which form a compact domain to aid in substrate recognition and subcellular localization mediated by protein-protein interactions. The PBD also contributes to the regulation of PLK kinase activity at specific subcellular locations at specific time points [16]. PLK2 regulates centriole duplication, while PLK3 is involved in DNA replication and is a stress response mediator [17,18]. PLK4 is structurally divergent, characterized by a single polo box that is capable of intermolecular homodimerization, and a conserved central region called a ‘cryptic polo box’ which is necessary for its functions in centriole duplication [19,20]. PLK4 may have a markedly different recognition motif and binding mode [21,22]. PLK5 is a pseudo kinase which lacks an intact kinase domain, but still contains a PBD domain with two polo boxes. PLK5 is expressed in differentiated cells and seem to have nervous system specific roles [23].
Approaching complexity: systems biology and ms-based techniques to address immune signaling
Published in Expert Review of Proteomics, 2020
Joseph Gillen, Caleb Bridgwater, Aleksandra Nita-Lazar
Two elegant reports used multi-omics to analyze the toll-like receptor (TLR) pathways. In the report by Chevrier et al., transcriptomics, proteomics, and phosphoproteomics were combined to analyze the responses of bone marrow-derived dendritic cells (BMDCs) to stimulations with several TLR agonists. In their transcriptomics data, 280 genes were found to change expression following stimulation. The 280 potential targets were then reduced to a subset of 23 with strong differential expression and their previously unknown relationship with TLR pathway. A further analysis of these candidate proteins identified one, Polo-like kinase 2 (Plk2), as a novel non-regulator of the TLR pathway. Interestingly, while the knockdown or knockout of Plk2 had no effect on the TLR pathway alone, when both Plk2 and Plk4, a related kinase that had similar differential expression, were inhibited, the antiviral responses of the BMDCs was significantly decreased. Furthermore, treatment with a pan-specific Plk inhibitor lead to modified production of antiviral RNAs, secretion of antiviral proteins, and phosphorylation of 413 distinct proteins following stimulation with LPS [60].
Gene expression profiling of rat livers after continuous whole-body exposure to low-dose rate of gamma rays
Published in International Journal of Radiation Biology, 2018
The polo-like kinase family consists of five members (Plk1 to Plk5) that are characterized by their conserved C-terminal polo box and N-terminal kinase domains. Polo-like kinases are crucial regulators of various aspects of cell division, including mitosis, cytokinesis, and the centrosome (Archambault and Glover 2009). Plk2 is considered to be responsive to IR, since its IR-induced expression has been observed in high-throughput transcriptome profiling experiments (Burns and El-Deiry 2003; Sokolov et al. 2011, 2015). In this study, the expression level of Plk2 was increased a 2.09-fold following IR exposure. Although the exact role of Plk2 is not well defined, its over-expression is thought to increase cell survival under stress conditions (Matsumoto et al. 2009).