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https://www.readbyqxmd.com/read/28434945/prognostic-biomarker-identification-through-integrating-the-gene-signatures-of-hepatocellular-carcinoma-properties
#1
Jialin Cai, Bin Li, Yan Zhu, Xuqian Fang, Mingyu Zhu, Mingjie Wang, Shupeng Liu, Xiaoqing Jiang, Jianming Zheng, XinXin Zhang, Peizhan Chen
Many molecular classification and prognostic gene signatures for hepatocellular carcinoma (HCC) patients have been established based on genome-wide gene expression profiling; however, their generalizability is unclear. Herein, we systematically assessed the prognostic effects of these gene signatures and identified valuable prognostic biomarkers by integrating these gene signatures. With two independent HCC datasets (GSE14520, N=242 and GSE54236, N=78), 30 published gene signatures were evaluated, and 11 were significantly associated with the overall survival (OS) of postoperative HCC patients in both datasets...
April 12, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28430399/targeting-conformational-activation-of-cdk2-kinase
#2
Morgan Pellerano, Sergey Tcherniuk, Corine Perals, Thi Nhu Ngoc Van, Elsa Garcin, Florence Mahuteau-Betzer, Marie-Paule Teulade-Fichou, May C Morris
Cyclin-dependent kinases constitute attractive pharmacological targets for cancer therapeutics, yet inhibitors in clinical trials target the ATP-binding pocket of the CDK and therefore suffer from limited selectivity and emergence of resistance. The more recent development of allosteric inhibitors targeting conformational plasticity of protein kinases offers promising perspectives for therapeutics. In particular tampering with T-loop dynamics of CDK2 kinase would provide a selective means of inhibiting this kinase, by preventing its conformational activation...
April 21, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/28428242/mapping-the-synthetic-dosage-lethality-network-of-cdk1-cdc28
#3
Christine Zimmermann, Ignacio Garcia, Manja Omerzu, Pierre Chymkowitch, Beibei Zhang, Jorrit M Enserink
Cdk1 (Cdc28 in yeast) is a cyclin dependent kinase (CDK) essential for cell cycle progression and cell division in normal cells. However, CDK activity also underpins proliferation of tumor cells, making it a relevant study subject. While numerous targets and processes regulated by Cdc28 have been identified, the exact functions of Cdc28 are only partially understood. To further explore the functions of Cdc28 we systematically overexpressed approximately 4800 genes in wild-type cells and in cells with artificially reduced Cdc28 activity...
April 19, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28426773/correction-cdk1-is-a-synthetic-lethal-target-for-kras-mutant-tumours
#4
Sara Costa-Cabral, Rachel Brough, Asha Konde, Marieke Aarts, James Campbell, Eliana Marinari, Jenna Riffell, Alberto Bardelli, Christopher Torrance, Christopher J Lord, Alan Ashworth
[This corrects the article DOI: 10.1371/journal.pone.0149099.].
2017: PloS One
https://www.readbyqxmd.com/read/28420180/synthesis-and-antiproliferative-activity-of-novel-all-trans-retinoic-acid-podophyllotoxin-conjugate-towards-human-gastric-cancer-cells
#5
Lei Zhang, Jing Wang, Lai Liu, Chengyue Zheng, Yang Wang
With the purpose of creating a multifunctional drug for gastric cancer treatment, a novel all-trans-retinoic acid (ATRA) conjugate with podophyllotoxin (PPT) was designed and synthesized, and its in vitro antiproliferative activity was evaluated against human gastric cancer cell lines using CCK-8 assay. The conjugate, P-A, exhibited significant anticancer activity against MKN-45 and BGC-823 cells with IC50 values of 0.419 ± 0.032 and 0.202 ± 0.055 μM, respectively. Moreover, P-A efficiently triggered cell cycle arrest and induced apoptosis in MKN-45 and BGC-823 cells due to modulation of cell cycle arrest- (CDK1, CDK2, CyclinA and CyclinB1) and apoptosis- (cleaved caspase-3, -8 and -9) related proteins, respectively...
April 17, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28416456/licoricidin-inhibits-the-growth-of-sw480-human-colorectal-adenocarcinoma-cells-in-vitro-and-in-vivo-by-inducing-cycle-arrest-apoptosis-and-autophagy
#6
Shuai Ji, Shunan Tang, Kai Li, Ziwei Li, Wenfei Liang, Xue Qiao, Qi Wang, Siwang Yu, Min Ye
Licorice (Glycyrrhiza uralensis Fisch.) possesses significant anti-cancer activities, but the active ingredients and underlying mechanisms have not been revealed. By screening the cytotoxic activities of 122 licorice compounds against SW480 human colorectal adenocarcinoma cells, we found that licoricidin (LCD) inhibited SW480 cell viability with an IC50 value of 7.2μM. Further studies indicated that LCD significantly induced G1/S cell cycle arrest and apoptosis in SW480 cells, accompanied by inhibition of cyclins/CDK1 expression and activation of caspase-dependent pro-apoptotic signaling...
April 14, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28410121/nitric-oxide-signaling-during-meiotic-cell-cycle-regulation-in-mammalian-oocytes
#7
Meenakshi Tiwari, Shilpa Prasad, Ashutosh N Pandey, Karuppanan V Premkumar, Anima Tripathi, Anumegha Gupta, Doddalingaiah R Chetan, Pramod K Yadav, Tulsidas G Shrivastav, Shail K Chaube
  Nitric oxide (NO) acts as a major signal molecules and modulate physiology of mammalian oocytes. Ovarian follicles generate large amount of NO through nitric oxide synthase (NOS) pathway to maintain diplotene arrest in preovulatory oocytes. Removal of oocytes from follicular microenvironment or follicular rupture during ovulation disrupt the flow of NO from granulosa cells to the oocyte that results a transient decrease of oocyte cytoplasmic NO level. Decreased NO level reduces cyclic nucleotides level by inactivating guanylyl cyclases directly or indirectly...
June 1, 2017: Frontiers in Bioscience (Scholar Edition)
https://www.readbyqxmd.com/read/28408662/the-gdnf-responsive-phosphoprotein-landscape-identifies-raptor-phosphorylation-required-for-spermatogonial-progenitor-cell-proliferation
#8
Min Wang, Yueshuai Guo, Mei Wang, Tao Zhou, Yuanyuan Xue, Guihua Du, Xiang Wei, Jing Wang, Lin Qi, Hao Zhang, Lufan Li, Lan Ye, Xuejiang Guo, Xin Wu
Cytokine-dependent renewal of stem cells is a fundamental requisite for tissue homeostasis and regeneration. Spermatogonial progenitor cells (SPCs) including stem cells support life-long spermatogenesis and male fertility, but pivotal phosphorylation events that regulate fate decisions in SPCs remain unresolved. Here, we described a quantitative mass-spectrometry-based proteomic and phosphoproteomic analyses of SPCs following sustained stimulation with glial cell-derived neurotrophic factor (GDNF), an extrinsic factor supporting SPC proliferation...
April 13, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28401191/inhibition-of-ezh2-degradation-as-a-novel-approach-to-overcome-drug-resistance-in-acute-myeloid-leukemia
#9
Stefanie Göllner, Carsten Müller-Tidow
The polycomb protein enhancer of zeste homolog 2 (EZH2) may have a dual role in cancer pathogenesis acting as an oncogene or as a tumor suppressor depending on the cancer type. We recently demonstrated that proteasomal degradation of EZH2 resulting from cyclin-dependent kinase 1 (CDK1)-induced phosphorylation at Threonine (T) 487 represents a novel mechanism of drug resistance in acute myeloid leukemia (AML). Our findings suggest that restoration of EZH2 protein is a viable approach to overcome therapy resistance in AML...
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28396830/the-g2-checkpoint-a-node-based-molecular-switch
#10
Mark C de Gooijer, Arnout van den Top, Irena Bockaj, Jos H Beijnen, Thomas Würdinger, Olaf van Tellingen
Tight regulation of the eukaryotic cell cycle is paramount to ensure genomic integrity throughout life. Cell cycle checkpoints are present in each phase of the cell cycle and prevent cell cycle progression when genomic integrity is compromised. The G2 checkpoint is an intricate signaling network that regulates the progression of G2 to mitosis (M). We propose here a node-based model of G2 checkpoint regulation, in which the action of the central CDK1-cyclin B1 node is determined by the concerted but opposing activities of the Wee1 and cell division control protein 25C (CDC25C) nodes...
April 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28396045/drosophila-p115-is-required-for-cdk1-activation-and-g2-m-cell-cycle-transition
#11
Consuelo Ibar, Álvaro Glavic
Golgi complex inheritance and its relationship with the cell cycle are central in cell biology. Golgi matrix proteins, known as golgins, are one of the components that underlie the shape and functionality of this organelle. In mammalian cells, golgins are phosphorylated during mitosis to allow fragmentation of the Golgi ribbon and they also participate in spindle dynamics; both processes are required for cell cycle progression. Little is known about the function of golgins during mitosis in metazoans in vivo...
April 7, 2017: Mechanisms of Development
https://www.readbyqxmd.com/read/28392503/mechanisms-of-the-anti-tumor-activity-of-methyl-2-5-fluoro-2-hydroxyphenyl-1-h-benzo-d-imidazole-5-carboxylate-against-breast-cancer-in-vitro-and-in-vivo
#12
Mohadeseh Hasanpourghadi, Ashok Kumar Pandurangan, Chandrabose Karthikeyan, Piyush Trivedi, Mohd Rais Mustafa
Microtubule Targeting Agents (MTAs) induce cell death through mitotic arrest, preferentially affecting rapidly dividing cancer cells over slowly proliferating normal cells. Previously, we showed that Methyl 2-(-5-fluoro-2-hydroxyphenyl)-1H-benzo[d]imidazole-5-carboxylate (MBIC) acts as a potential MTA. In this study, we demonstrated that MBIC exhibits greater toxicity towards non-aggressive breast cancer cell-line, MCF-7 (IC50 = 0.73 ± 0.0 μM) compared to normal fibroblast cell-line, L-cells (IC50 = 59.6 ± 2...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28387346/plk1-regulates-the-repressor-function-of-foxm1b-by-inhibiting-its-interaction-with-the-retinoblastoma-protein
#13
Nishit K Mukhopadhyay, Vaibhav Chand, Akshay Pandey, Dragana Kopanja, Janai R Carr, Yi-Ju Chen, Xiubei Liao, Pradip Raychaudhuri
FoxM1b is a cell cycle-regulated transcription factor, whose over-expression is a marker for poor outcome in cancers. Its transcriptional activation function requires phosphorylation by Cdk1 or Cdk2 that primes FoxM1b for phosphorylation by Plk1, which triggers association with the co-activator CBP. FoxM1b also possesses transcriptional repression function. It represses the mammary differentiation gene GATA3 involving DNMT3b and Rb. We investigated what determines the two distinct functions of FoxM1b: activation and repression...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28386317/alisertib-induces-g2-m-arrest-apoptosis-and-autophagy-via-pi3k-akt-mtor-and-p38-mapk-mediated-pathways-in-human-glioblastoma-cells
#14
Zheng Liu, Feng Wang, Zhi-Wei Zhou, He-Chun Xia, Xin-Yu Wang, Yin-Xue Yang, Zhi-Xu He, Tao Sun, Shu-Feng Zhou
Glioblastoma (GBM) is the most common brain tumor with poor response to current therapeutics. Alisertib (ALS), a second-generation selective Aurora kinase A (AURKA) inhibitor, has shown potent anticancer effects on solid tumors in animal studies. This study aimed to investigate the killing effect of ALS on GBM cell line DAOY and the possible underlying mechanisms using both bioinformatic and cell-based approaches. Our molecular docking showed that ALS preferentially bound AURKA over AURKB via hydrogen bond formation, charge interaction, and π-π stacking...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28385078/paris-polyphylla-suppresses-proliferation-and-vasculogenic-mimicry-of-human-osteosarcoma-cells-and-inhibits-tumor-growth-in-vivo
#15
Nan Yao, Ke Ren, Yimin Wang, Qiaomei Jin, Xiao Lu, Yan Lu, Cuihua Jiang, Dongjian Zhang, Jun Lu, Chen Wang, Jiege Huo, Yong Chen, Jian Zhang
Paris polyphylla, a traditional antipyretic-detoxicate chinese medicinal herb, has been applied extensively in cancer treatments for nearly 2000 years. The purpose of the present study is to evaluate the potential anti-osteosarcoma effects of Paris polyphylla ethanol extract (PPEE) and to investigate its underlying mechanisms. The antiproliferation activity of PPEE was tested on 143B, MG-63, U-2 OS and hFOB1.19 cells using MTT assay. The pro-apoptotic and cell cycle arrest effects of PPEE were confirmed by Hoechst 33342 staining and flow cytometry...
April 6, 2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/28381422/polo-kinase-mediates-the-phosphorylation-and-cellular-localization-of-nuf-fip3-a-rab11-effector
#16
Lotti Brose, Justin Crest, Li Tao, William Sullivan
Animal cytokinesis involves both actin-myosin based contraction and vesicle-mediated membrane addition. In many cell types, including early Drosophila embryos, Nuf/FIP3, a Rab11 effector, mediates recycling endosome (RE)-based vesicle delivery to the cytokinesis furrow. Nuf exhibits a cell cycle-regulated concentration at the centrosome that is accompanied by dramatic changes in its phosphorylation state. Here we demonstrate maximal phosphorylation of Nuf occurs at prophase, when centrosome-associated Nuf disperses throughout the cytoplasm...
April 5, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28377371/molecular-basis-for-cdk1-regulated-timing-of-mis18-complex-assembly-and-cenp-a-deposition
#17
Frances Spiller, Bethan Medina-Pritchard, Maria Alba Abad, Martin A Wear, Oscar Molina, William C Earnshaw, A Arockia Jeyaprakash
The centromere, a chromosomal locus that acts as a microtubule attachment site, is epigenetically specified by the enrichment of CENP-A nucleosomes. Centromere maintenance during the cell cycle requires HJURP-mediated CENP-A deposition, a process regulated by the Mis18 complex (Mis18α/Mis18β/Mis18BP1). Spatial and temporal regulation of Mis18 complex assembly is crucial for its centromere association and function. Here, we provide the molecular basis for the assembly and regulation of the Mis18 complex. We show that the N-terminal region of Mis18BP1 spanning amino acid residues 20-130 directly interacts with Mis18α/β to form the Mis18 complex...
April 4, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28368408/jnks-function-as-cdk4-activating-kinases-by-phosphorylating-cdk4-and-p21
#18
B Colleoni, S Paternot, J M Pita, X Bisteau, K Coulonval, R J Davis, E Raspé, P P Roger
Cyclin D-CDK4/6 are the first cyclin-dependent kinase (CDK) complexes to be activated by mitogenic/oncogenic pathways. They have a central role in the cell multiplication decision and in its deregulation in cancer cells. We identified T172 phosphorylation of CDK4 rather than cyclin D accumulation as the distinctly regulated step determining CDK4 activation. This finding challenges the view that the only identified metazoan CDK-activating kinase, cyclin H-CDK7-Mat1 (CAK), which is constitutively active, is responsible for the activating phosphorylation of all cell cycle CDKs...
April 3, 2017: Oncogene
https://www.readbyqxmd.com/read/28360195/g1-s-phase-progression-is-regulated-by-plk1-degradation-through-the-cdk1-%C3%AE-trcp-axis
#19
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/28359799/paxillin-and-embryonic-polyadenylation-binding-protein-epabp-engage-to-regulate-androgen-dependent-xenopus-laevis-oocyte-maturation-a-model-of-kinase-dependent-regulation-of-protein-expression
#20
Susanne U Miedlich, Manisha Taya, Melissa Rasar Young, Stephen R Hammes
Steroid-triggered Xenopus laevis oocyte maturation is an elegant physiologic model of nongenomic steroid signaling, as it proceeds completely independent of transcription. We previously demonstrated that androgens are the main physiologic stimulator of oocyte maturation in Xenopus oocytes, and that the adaptor protein paxillin plays a crucial role in mediating this process through a positive feedback loop in which paxillin first enhances Mos protein translation, ensued by Erk2 activation and Erk-dependent phosphorylation of paxillin on serine residues...
March 28, 2017: Molecular and Cellular Endocrinology
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