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Polo-like kinase

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https://www.readbyqxmd.com/read/28436952/playing-polo-during-mitosis-plk1-takes-the-lead
#1
REVIEW
G Combes, I Alharbi, L G Braga, S Elowe
Polo-like kinase 1 (PLK1), the prototypical member of the polo-like family of serine/threonine kinases, is a pivotal regulator of mitosis and cytokinesis in eukaryotes. Many layers of regulation have evolved to target PLK1 to different subcellular structures and to its various mitotic substrates in line with its numerous functions during mitosis. Collective work is starting to illuminate an important set of substrates for PLK1: the mitotic kinases that together ensure the fidelity of the cell division process...
April 24, 2017: Oncogene
https://www.readbyqxmd.com/read/28432586/cdc20-with-malignant-progression-and-poor-prognosis-of-astrocytoma-revealed-by-analysis-on-gene-expression
#2
Yiming Ding, Shuqing Yu, Zhaoshi Bao, Yanwei Liu, Tingyu Liang
The malignant transformation of astrocytoma may result from the accumulation of multiple genetic alterations. Current research shows that diffuse astrocytoma (AIIs, WHO grade II) is inherently predisposed to recur locally, and to spontaneously progress to anaplastic astrocytoma (AAIIIs, WHO grade III) and eventually secondary glioblastoma (sGBMIVs, WHO grade IV). The aim of the study was to identify and validate the important gene(s) associated with malignant progression and poor prognosis of astrocytoma. Average expression levels of 82 samples (35 AIIs, 13 AAIIIs and 34 sGBMIVs) were compared to each other through no-paired student test...
April 21, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28430578/involvement-of-polo-like-kinase-1-plk1-in-quiescence-regulation-of-cancer-stem-like-cells-of-the-gastric-cancer-cell-lines
#3
Lin Zhu, Sheng Xing, Li Zhang, Jian-Min Yu, Cheng Lin, Wei-Jun Yang
Cancer stem cells (CSCs) have been hypothesized to initiate tumor growth and be resistant to chemoradiotherapy, and these processes appear to be closely related to CSC quiescence. Here, a CSC-like cell population with a high level of CD44 expression was obtained from the human gastric cancer cell lines MKN45 and MKN74. Using a PKH26-labeling retention assay, quiescent CSC-like cells with low levels of Ki67 and PCNA expression were found in spheres formed in serum-free medium, and exhibited resistance to drug and radiation treatments...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416758/synergistic-interactions-between-plk1-and-hdac-inhibitors-in-non-hodgkin-s-lymphoma-cells-occur-in-vitro-and-in-vivo-and-proceed-through-multiple-mechanisms
#4
Tri Nguyen, Rebecca Parker, Elisa Hawkins, Beata Holkova, Victor Yazbeck, Akhil Kolluri, Maciej Kmieciak, Mohamed Rahmani, Steven Grant
Interactions between the polo-like kinase 1 (PLK1) inhibitor volasertib and the histone deacetylase inhibitor (HDACI) belinostat were examined in diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) cells in vitro and in vivo. Exposure of DLBCL cells to very low concentrations of volasertib in combination with belinostat synergistically increased cell death (apoptosis). Similar interactions occurred in GC-, ABC-, double-hit DLBCL cells, MCL cells, bortezomib-resistant cells and primary lymphoma cells...
February 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416751/proteasome-inhibition-enhances-the-efficacy-of-volasertib-induced-mitotic-arrest-in-aml-in-vitro-and-prolongs-survival-in-vivo
#5
Dominik Schnerch, Julia Schüler, Marie Follo, Julia Felthaus, Dagmar Wider, Kathrin Klingner, Christine Greil, Justus Duyster, Monika Engelhardt, Ralph Wäsch
Elderly and frail patients, diagnosed with acute myeloid leukemia (AML) and ineligible to undergo intensive treatment, have a dismal prognosis. The small molecule inhibitor volasertib induces a mitotic block via inhibition of polo-like kinase 1 and has shown remarkable anti-leukemic activity when combined with low-dose cytarabine. We have demonstrated that AML cells are highly vulnerable to cell death in mitosis yet manage to escape a mitotic block through mitotic slippage by sustained proteasome-dependent slow degradation of cyclin B...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415805/regulatory-functional-territory-of-plk-1-and-their-substrates-beyond-mitosis
#6
REVIEW
Shiv Kumar, Garima Sharma, Chiranjib Chakraborty, Ashish Ranjan Sharma, Jaebong Kim
Polo-like kinase 1 (PLK-1) is a well-known (Ser/Thr) mitotic protein kinase and is considered as a proto-oncogene. As hyper-activation of PLK-1 is broadly associated with poor prognosis and cancer progression, it is one of the most extensively studied mitotic kinases. During mitosis, PLK-1 regulates various cell cycle events, such as spindle pole maturation, chromosome segregation and cytokinesis. However, studies have demonstrated that the role of PLK-1 is not only restricted to mitosis, but PLK-1 can also regulate other vital events beyond mitosis, including transcription, translation, ciliogenesis, checkpoint adaptation and recovery, apoptosis, chromosomes dynamics etc...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413501/usp39-regulates-the-growth-of-smmc-7721-cells-via-foxm1
#7
Xianwen Yuan, Xitai Sun, Xiaolei Shi, Chunping Jiang, Decai Yu, Weiwei Zhang, Yitao Ding
The present study investigated ubiquitin specific peptidase 39 (USP39) gene knockdown on SMMC-7721 cells in vitro and in vivo, and the role of USP39 in regulating the growth of hepatocellular carcinoma (HCC). Two small interfering RNAs (siRNA) were constructed, which targeted the USP39 gene and control sequences were synthesized and inserted into a pGCSIL-GFP lentiviral vector. The full length of USP39 cDNA was amplified by polymerase chain reaction (PCR) and cloned into pEGFP-N2, and the recombinant plasmids were transfected into cells...
April 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28407751/transcriptome-analysis-reveals-potential-mechanisms-underlying-differential-heart-development-in-fast-and-slow-growing-broilers-under-heat-stress
#8
Jibin Zhang, Carl J Schmidt, Susan J Lamont
BACKGROUND: Modern fast-growing broilers are susceptible to heart failure under heat stress because their relatively small hearts cannot meet increased need of blood pumping. To improve the cardiac tolerance to heat stress in modern broilers through breeding, we need to find the important genes and pathways that contribute to imbalanced cardiac development and frequent occurrence of heat-related heart dysfunction. Two broiler lines - Ross 708 and Illinois - were included in this study as a fast-growing model and a slow-growing model respectively...
April 13, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28405163/enhancing-sirna-based-cancer-therapy-using-a-new-ph-responsive-activatable-cell-penetrating-peptide-modified-liposomal-system
#9
Bai Xiang, Xue-Li Jia, Jin-Long Qi, Li-Ping Yang, Wei-Hong Sun, Xiao Yan, Shao-Kun Yang, De-Ying Cao, Qing Du, Xian-Rong Qi
As a potent therapeutic agent, small interfering RNA (siRNA) has been exploited to silence critical genes involved in tumor initiation and progression. However, development of a desirable delivery system is required to overcome the unfavorable properties of siRNA such as its high degradability, molecular size, and negative charge to help increase its accumulation in tumor tissues and promote efficient cellular uptake and endosomal/lysosomal escape of the nucleic acids. In this study, we developed a new activatable cell-penetrating peptide (ACPP) that is responsive to an acidic tumor microenvironment, which was then used to modify the surfaces of siRNA-loaded liposomes...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28402276/cell-cycle-protein-bora-serves-as-a-novel-poor-prognostic-factor-in-multiple-adenocarcinomas
#10
Qiong-Xia Zhang, Rui Gao, Jin Xiang, Zhong-Yu Yuan, Yuan-Min Qian, Min Yan, Zi-Feng Wang, Quentin Liu, Hai-Dong Zhao, Chang-Hong Liu
Cell cycle protein Bora has been identified to integrate the functions of three major mitotic kinases: Cyclin-dependent kinase-1, Polo-like kinase-1, and Aurora A kinase. Overexpression of Bora disrupts spindle assembly and causes genomic instability. However, the clinical relevance of Bora in cancer remains unclear. In this study, we examined the expression of Bora and its association with clinical characteristics in breast (n = 538), lung (n = 144) and gastric (n = 77) adenocarcinomas. We found that Bora was overexpressed in primary breast cancer tissues compared to paired non-cancerous tissues...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28401599/foxm1-transcription-factor-a-new-component-of-chronic-myeloid-leukemia-stem-cell-proliferation-advantage
#11
Manuela Mancini, Fausto Castagnetti, Simona Soverini, Elisa Leo, Caterina De Benedittis, Gabriele Gugliotta, Gianantonio Rosti, Luana Bavaro, Sara De Santis, Cecilia Monaldi, Margherita Martelli, Maria Alessandra Santucci, Michele Cavo, Giovanni Martinelli
FOXM1 transcription factor is a central component of tumor initiation, growth and progression due to its multiple effects on cell cycle, DNA repair, angiogenesis and invasion, chromatin, protein anabolism and cell adhesion. Moreover, FOXM1 interacts with β-catenin promoting its nuclear import and transcriptional activation. Here we show that FOXM1 is involved in the advantage of chronic myeloid leukemia hematopoiesis over the normal counterpart. FOXM1 hyper-activation associated with BCR-ABL1 results from phosphorylation by the fusion protein kinase-dependent activation of Polo-like kinase 1...
April 12, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28401181/kat2-mediated-plk4-acetylation-contributes-to-genomic-stability-by-preserving-centrosome-number
#12
Marjorie Fournier, László Tora
We have recently identified the first human lysine (K) acetyltransferase 2A and 2B (called KAT2A/2B; known also as GCN5/PCAF, respectively)-dependent acetylome and revealed a mechanism by which KAT2A/2B-mediated acetylation of serine/threonine polo-like kinase 4 (PLK4) maintains correct centrosome number in human cells, therefore contributing to the maintenance of genome stability.(1).
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28400058/the-snk-and-spar-signaling-pathway-changes-in-hippocampal-neurons-treated-with-amyloid-beta-peptide-in-vitro
#13
Hua Sui, Libin Zhan, Xinping Niu, Lina Liang, Xin Li
Amyloid-β peptide (Aβ) is believed to be a primary cause of Alzheimer's disease. Many studies have demonstrated that Aβ causes morphological and functional alterations of dendritic spines, leading to synaptic dysfunction, but the effect of Aβ on damage to synaptic functions is not fully understood. Spine-associated Rap guanosine triphosphatase-activating protein (SPAR) is an important regulator of activity-dependent remodeling of synapses and is critically involved in both mature dendritic spine formation and the maintenance of spine maturity...
March 22, 2017: Neuropeptides
https://www.readbyqxmd.com/read/28398638/a-functional-screening-of-the-kinome-identifies-the-polo-like-kinase-4-as-a-potential-therapeutic-target-for-malignant-rhabdoid-tumors-and-possibly-other-embryonal-tumors-of-the-brain
#14
Simone Treiger Sredni, Mario Suzuki, Jian-Ping Yang, Jacek Topczewski, Anders W Bailey, Tufan Gokirmak, Jeffrey N Gross, Alexandre de Andrade, Akihide Kondo, David R Piper, Tadanori Tomita
PURPOSE: Malignant rhabdoid tumors (MRTs) are deadly embryonal tumors of the infancy. With poor survival and modest response to available therapies, more effective and less toxic treatments are needed. We hypothesized that a systematic screening of the kinome will reveal kinases that drive rhabdoid tumors and can be targeted by specific inhibitors. METHODS: We individually mutated 160 kinases in a well-characterized rhabdoid tumor cell line (MON) using lentiviral clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)...
April 11, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28380042/genetic-and-pharmacological-inhibition-of-ttk-impairs-pancreatic-cancer-cell-line-growth-by-inducing-lethal-chromosomal-instability
#15
Jeran K Stratford, Feng Yan, Rebecca A Hill, Michael B Major, Lee M Graves, Channing J Der, Jen Jen Yeh
Pancreatic ductal adenocarcinoma, which accounts for the majority of pancreatic cancers, is a lethal disease with few therapeutic options. Genomic profiling of pancreatic ductal adenocarcinoma has identified a complex and heterogeneous landscape. Understanding the molecular characteristics of pancreatic ductal adenocarcinoma will facilitate the identification of potential therapeutic strategies. We analyzed the gene expression profiles of primary tumors from patients compared to normal pancreas and identified high co-overexpression of core components of the spindle assembly checkpoint, including the protein kinase TTK (also known as MPS-1)...
2017: PloS One
https://www.readbyqxmd.com/read/28360195/g1-s-phase-progression-is-regulated-by-plk1-degradation-through-the-cdk1-%C3%AE-trcp-axis
#16
Servando Giráldez, María Galindo-Moreno, M Cristina Limón-Mortés, A Cristina Rivas, Joaquín Herrero-Ruiz, Mar Mora-Santos, Carmen Sáez, Miguel Á Japón, Maria Tortolero, Francisco Romero
Polo-like kinase 1 (PLK1) is a serine/threonine kinase involved in several stages of the cell cycle, including the entry and exit from mitosis, and cytokinesis. Furthermore, it has an essential role in the regulation of DNA replication. Together with cyclin A, PLK1 also promotes CDH1 phosphorylation to trigger its ubiquitination and degradation, allowing cell cycle progression. The PLK1 levels in different type of tumors are very high compared to normal tissues, which is consistent with its role in promoting proliferation...
March 30, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28351953/sphingosine-1-phosphate-signaling-through-its-receptor-s1p5-promotes-chromosome-segregation-and-mitotic-progression
#17
Guillaume Andrieu, Adeline Ledoux, Sophie Branka, Magalie Bocquet, Julia Gilhodes, Thierry Walzer, Kousuke Kasahara, Masaki Inagaki, Roger A Sabbadini, Olivier Cuvillier, Anastassia Hatzoglou
Sphingosine kinase 1 (SphK1) promotes cell proliferation and survival, and its abundance is often increased in tumors. SphK1 produces the signaling lipid sphingosine 1-phosphate (S1P), which activates signaling cascades downstream five G protein-coupled receptors (S1P1-5) to modulate vascular and immune system function and promote proliferation. We identified a new function of the SphK1-S1P pathway specifically in the control of mitosis. SphK1 depletion in HeLa cells caused prometaphase arrest, whereas its overexpression or activation accelerated mitosis...
March 28, 2017: Science Signaling
https://www.readbyqxmd.com/read/28346135/polo-like-kinase-dependent-phosphorylation-of-the-synaptonemal-complex-protein-syp-4-regulates-double-strand-break-formation-through-a-negative-feedback-loop
#18
Saravanapriah Nadarajan, Talley J Lambert, Elisabeth Altendorfer, Jinmin Gao, Michael D Blower, Jennifer C Waters, Monica P Colaiácovo
The synaptonemal complex (SC) is an ultrastructurally conserved proteinaceous structure that holds homologous chromosomes together and is required for the stabilization of pairing interactions and the completion of crossover (CO) formation between homologs during meiosis I. Here, we identify a novel role for a central region component of the SC, SYP-4, in negatively regulating formation of recombination-initiating double-strand breaks (DSBs) via a feedback loop triggered by crossover designation in C. elegans...
March 27, 2017: ELife
https://www.readbyqxmd.com/read/28344766/phosphorylation-of-lsd1-by-plk1-promotes-its-chromatin-release-during-mitosis
#19
Bin Peng, Ruifeng Shi, Weiwei Jiang, Yue-He Ding, Meng-Qiu Dong, Wei-Guo Zhu, Xingzhi Xu
BACKGROUND: Lysine-specific histone demethylase 1 (LSD1) modulates chromatin status through demethylation of H3K4 and H3K9. It has been demonstrated that LSD1 is hyperphosphorylated and dissociates from chromatin during mitosis. However, the molecular mechanism of LSD1 detachment is unknown. RESULTS: In this report, we found that polo-like kinase 1 (PLK1) directly interacted with LSD1 and phosphorylated LSD1 at Ser-126 . Nocodazole-induced metaphase arrest promoted release of LSD1 from chromatin, and the phosphorylation-defective mutant LSD1 (S126A) failed to dissociate from chromatin upon nocodazole treatment...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/28341486/polo-like-kinase-1-expression-is-suppressed-by-ccaat-enhancer-binding-protein-%C3%AE-to-mediate-colon-carcinoma-cell-differentiation-and-apoptosis
#20
Nirmalya Dasgupta, Bhupesh Kumar Thakur, Atri Ta, Sayan Das, George Banik, Santasabuj Das
BACKGROUND: Human polo-like kinase 1 (PLK1), a highly conserved serine/threonine kinase is a key player in several essential cell-cycle events. PLK1 is considered an oncogene and its overexpression often correlates with poor prognosis of cancers, including colorectal cancer (CRC). However, regulation of PLK1 expression in colorectal cells was never studied earlier and it is currently unknown if PLK1 regulates differentiation and apoptosis of CRC. METHODS: PLK1 expression was analyzed by real-time PCR and western blotting...
March 21, 2017: Biochimica et Biophysica Acta
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