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https://www.readbyqxmd.com/read/28629311/cell-cycle-arrest-and-apoptosis-induction-activity-of-nitidine-chloride-on-acute-myeloid-leukemia-cells
#1
Peng Li, Shuxin Yan, Xin Dong, Zhao Li, Yu Qiu, Chunyan Ji, Jingru Zhang, Min Ji, Wei Li, Hongchun Wang, Zhi Liu, Xing Li Wang, Jingjing Ye, Daoxin Ma
: Background: Acute myeloid leukemia (AML) is the most common hematological malignancy in adults, characterized by distorted proliferation and development of myeloid cells and their precursors in the bone marrow. Nitidine chloride, a naturally occurring alkaloid, has been identified to possess antitumor activity. However, the effects of nitidine chloride on acute myeloid leukemia cells and its underlying mechanisms have not been elucidated. Here we investigated the cellular and molecular mechanism of the anti-leukemic effects of nitidine chloride...
June 19, 2017: Medicinal Chemistry
https://www.readbyqxmd.com/read/28607595/e2f8-is-a-potential-therapeutic-target-for-hepatocellular-carcinoma
#2
REVIEW
Yi Lv, Jia Xiao, Jing Liu, Feiyue Xing
E2F transcriptional factors are widely expressed in a number of tissues and organs, possessing many regulatory functions related to cellular proliferation, differentiation, DNA repair, cell-cycle and cell apoptosis. E2F8 is a recently identified member of the E2F family with a duplicated DNA-binding domain feature discriminated from E2F1-6, controlling gene expression in a dimerization partner-independent manner. It is indispensable for angiogenesis, lymphangiogenesis and embryonic development. Although E2F8 and E2F7 perform complementary and overlapping functions in many cell metabolisms, E2F8, but not E2F7, overexpresses remarkably in hepatocellular carcinoma (HCC) to facilitate the HCC occurrence and development via activating a E2F1/ Cyclin D1 signaling pathway to regulate the G1- to S-phase transition of cell cycle progression or transcriptionally suppressing CDK1 to induce hepatocyte polyploidization...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28600888/homeostatic-control-of-start-through-negative-feedback-between-cln3-cdk1-and-rim15-greatwall-kinase-in-budding-yeast
#3
Nicolas Talarek, Elisabeth Gueydon, Etienne Schwob
How cells coordinate growth and division is key for size homeostasis. Phosphorylation by G1-CDK of Whi5/Rb inhibitors of SBF/E2F transcription factors triggers irreversible S-phase entry in yeast and metazoans, but why this occurs at a given cell size is not fully understood. We show that the yeast Rim15-Igo1,2 pathway, orthologous to Gwl-Arpp19/ENSA, is up-regulated in early G1 and helps promoting START by preventing PP2ACdc55 to dephosphorylate Whi5. RIM15 overexpression lowers cell size while IGO1,2 deletion delays START in cells with low CDK activity...
June 10, 2017: ELife
https://www.readbyqxmd.com/read/28598010/dleu1-contributes-to-ovarian-carcinoma-tumourigenesis-and-development-by-interacting-with-mir-490-3p-and-altering-cdk1-expression
#4
Li-Li Wang, Kai-Xuan Sun, Dan-Dan Wu, Yin-Ling Xiu, Xi Chen, Shuo Chen, Zhi-Hong Zong, Xiu-Bo Sang, Yao Liu, Yang Zhao
Recently, a large number of studies have focused on the important role of long non-coding RNAs (lncRNAs) in metabolism and development and have found that abnormal lncRNA expression is associated with the pathogenesis and development of many diseases. The lncRNA DLEU1 is involved in many solid tumours and haematological malignancies. However, its role in epithelial ovarian carcinoma (EOC) and the associated molecular mechanisms has not been reported. In this study, quantitative reverse transcription-PCR (qRT-PCR) demonstrated higher lncRNADLEU1 expression in EOC tissues than in normal tissues...
June 9, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28596604/mir-143-and-mir-145-disrupt-the-cervical-epithelial-barrier-through-dysregulation-of-cell-adhesion-apoptosis-and-proliferation
#5
Lauren Anton, Ann DeVine, Luz-Jeannette Sierra, Amy G Brown, Michal A Elovitz
Molecular mechanisms regulating preterm birth (PTB)-associated cervical remodeling remain unclear. Prior work demonstrated an altered miRNA profile, with significant increases in miR-143 and miR-145, in cervical cells of women destined to have a PTB. The study objective was to determine the effect of miR-143 and miR-145 on the cervical epithelial barrier and to elucidate the mechanisms by which these miRNAs modify cervical epithelial cell function. Ectocervical and endocervical cells transfected with miR-negative control, miR-143 or miR-145 were used in cell permeability and flow cytometry assays for apoptosis and proliferation...
June 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28592245/in-silico-identification-of-potential-key-regulatory-factors-in-smoking-induced-lung-cancer
#6
Salem A El-Aarag, Amal Mahmoud, Medhat H Hashem, Hatem Abd Elkader, Alaa E Hemeida, Mahmoud ElHefnawi
BACKGROUND: Lung cancer is a leading cause of cancer-related death worldwide and is the most commonly diagnosed cancer. Like other cancers, it is a complex and highly heterogeneous disease involving multiple signaling pathways. Identifying potential therapeutic targets is critical for the development of effective treatment strategies. METHODS: We used a systems biology approach to identify potential key regulatory factors in smoking-induced lung cancer. We first identified genes that were differentially expressed between smokers with normal lungs and those with cancerous lungs, then integrated these differentially expressed genes (DEGs) with data from a protein-protein interaction database to build a network model with functional modules for pathway analysis...
June 7, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/28591578/plk1-activation-in-late-g2-sets-up-commitment-to-mitosis
#7
Lilia Gheghiani, Damarys Loew, Bérangère Lombard, Jörg Mansfeld, Olivier Gavet
Commitment to mitosis must be tightly coordinated with DNA replication to preserve genome integrity. While we have previously established that the timely activation of CyclinB1-Cdk1 in late G2 triggers mitotic entry, the upstream regulatory mechanisms remain unclear. Here, we report that Polo-like kinase 1 (Plk1) is required for entry into mitosis during an unperturbed cell cycle and is rapidly activated shortly before CyclinB1-Cdk1. We determine that Plk1 associates with the Cdc25C1 phosphatase and induces its phosphorylation before mitotic entry...
June 6, 2017: Cell Reports
https://www.readbyqxmd.com/read/28588300/pre-rc-protein-mcm7-depletion-promotes-mitotic-exit-by-inhibiting-cdk1-activity
#8
Dianpeng Zheng, Sichao Ye, Xiuyun Wang, Yongjun Zhang, Daoyu Yan, Xiangsheng Cai, Weihong Gao, Hongbo Shan, Yang Gao, Juanjuan Chen, Zhiming Hu, Hongwei Li, Jinlong Li
MCM7, a subunit of mini-chromosome maintenance proteins (MCM) complex, plays an important role in initiating DNA replication during the G1 phase and extending DNA strands during the S phase. Here, we demonstrated that MCM7 is not only sustained but maintains association with chromatin during M phase. Remarkably, MCM7 siRNA can accelerate mitotic exit. MCM7 depletion leads to CDK1 inactivation and promotes subsequent cohesin/RAD21 cleavage, which eventually leads to sister chromatin segregation. Moreover, MCM7 is co-localized with tubulin in the mitotic cells and MCM7 depletion results in aberrant mitosis...
June 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28586114/a-phosphokinome-based-screen-uncovers-new-drug-synergies-for-cancer-driven-by-liver-specific-gain-of-non-oncogenic-rtks
#9
Yannan Fan, Maria Arechederra, Sylvie Richelme, Fabrice Daian, Chiara Novello, Julien Calderaro, Luca Di Tommaso, Guillaume Morcrette, Sandra Rebouissou, Matteo Donadon, Emanuela Morenghi, Jessica Zucman-Rossi, Massimo Roncalli, Rosanna Dono, Flavio Maina
Genetic mutations leading to oncogenic variants of receptor tyrosine kinases (RTKs) are frequent events during tumorigenesis; however, the cellular vulnerability to non-oncogenic RTK fluctuations has not been characterized. Here, we demonstrated genetically that liver subtle increases in wild-type Met RTK levels are sufficient for spontaneous tumors in mice (Alb-R26(Met) ), conceptually illustrating how the shift from physiological to pathological conditions results from slight perturbations in signaling dosage...
June 6, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28576864/lin-41-and-oma-ribonucleoprotein-complexes-mediate-a-translational-repression-to-activation-switch-controlling-oocyte-meiotic-maturation-and-the-oocyte-to-embryo-transition-in-caenorhabditis-elegans
#10
Tatsuya Tsukamoto, Micah D Gearhart, Caroline A Spike, Gabriela Huelgas-Morales, Makaela Mews, Peter R Boag, Traude H Beilharz, David Greenstein
An extended meiotic prophase is a hallmark of oogenesis. Hormonal signaling activates the CDK1/cyclin B kinase to promote oocyte meiotic maturation, which involves nuclear and cytoplasmic events. Nuclear maturation encompasses nuclear envelope breakdown, meiotic spindle assembly, and chromosome segregation. Cytoplasmic maturation involves major changes in oocyte protein translation and cytoplasmic organelles and is poorly understood. In the nematode Caenorhabditis elegans, sperm release the major sperm protein (MSP) hormone to promote oocyte growth and meiotic maturation...
June 1, 2017: Genetics
https://www.readbyqxmd.com/read/28575661/recq5-helicase-cooperates-with-mus81-endonuclease-in-processing-stalled-replication-forks-at-common-fragile-sites-during-mitosis
#11
Stefano Di Marco, Zdenka Hasanova, Radhakrishnan Kanagaraj, Nagaraja Chappidi, Veronika Altmannova, Shruti Menon, Hana Sedlackova, Jana Langhoff, Kalpana Surendranath, Daniela Hühn, Rahul Bhowmick, Victoria Marini, Stefano Ferrari, Ian D Hickson, Lumir Krejci, Pavel Janscak
The MUS81-EME1 endonuclease cleaves late replication intermediates at common fragile sites (CFSs) during early mitosis to trigger DNA-repair synthesis that ensures faithful chromosome segregation. Here, we show that these DNA transactions are promoted by RECQ5 DNA helicase in a manner dependent on its Ser727 phosphorylation by CDK1. Upon replication stress, RECQ5 associates with CFSs in early mitosis through its physical interaction with MUS81 and promotes MUS81-dependent mitotic DNA synthesis. RECQ5 depletion or mutational inactivation of its ATP-binding site, RAD51-interacting domain, or phosphorylation site causes excessive binding of RAD51 to CFS loci and impairs CFS expression...
June 1, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28566733/a-benzothiazole-derivative-5g-induces-dna-damage-and-potent-g2-m-arrest-in-cancer-cells
#12
Mahesh Hegde, Supriya V Vartak, Chandagirikoppal V Kavitha, Hanumappa Ananda, Doddakunche S Prasanna, Vidya Gopalakrishnan, Bibha Choudhary, Kanchugarakoppal S Rangappa, Sathees C Raghavan
Chemically synthesized small molecules play important role in anticancer therapy. Several chemical compounds have been reported to damage the DNA, either directly or indirectly slowing down the cancer cell progression by causing a cell cycle arrest. Direct or indirect reactive oxygen species formation causes DNA damage leading to cell cycle arrest and subsequent cell death. Therefore, identification of chemically synthesized compounds with anticancer potential is important. Here we investigate the effect of benzothiazole derivative (5g) for its ability to inhibit cell proliferation in different cancer models...
May 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28562334/gene-co-expression-network-reveals-shared-modules-predictive-of-stage-and-grade-in-serous-ovarian-cancers
#13
Qian Sun, Haiyue Zhao, Cong Zhang, Ting Hu, Jianli Wu, Xingguang Lin, Danfeng Luo, Changyu Wang, Li Meng, Ling Xi, Kezhen Li, Junbo Hu, Ding Ma, Tao Zhu
Serous ovarian cancer (SOC) is the most lethal gynecological cancer. Clinical studies have revealed an association between tumor stage and grade and clinical prognosis. Identification of meaningful clusters of co-expressed genes or representative biomarkers related to stage or grade may help to reveal mechanisms of tumorigenesis and cancer development, and aid in predicting SOC patient prognosis. We therefore performed a weighted gene co-expression network analysis (WGCNA) and calculated module-trait correlations based on three public microarray datasets (GSE26193, GSE9891, and TCGA), which included 788 samples and 10402 genes...
May 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28562324/prolonged-mitotic-arrest-induced-by-wee1-inhibition-sensitizes-breast-cancer-cells-to-paclitaxel
#14
Cody W Lewis, Zhigang Jin, Dawn Macdonald, Wenya Wei, Xu Jing Qian, Won Shik Choi, Ruicen He, Xuejun Sun, Gordon Chan
Wee1 kinase is a crucial negative regulator of Cdk1/cyclin B1 activity and is required for normal entry into and exit from mitosis. Wee1 activity can be chemically inhibited by the small molecule MK-1775, which is currently being tested in phase I/II clinical trials in combination with other anti-cancer drugs. MK-1775 promotes cancer cells to bypass the cell-cycle checkpoints and prematurely enter mitosis. In our study, we show premature mitotic cells that arise from MK-1775 treatment exhibited centromere fragmentation, a morphological feature of mitotic catastrophe that is characterized by centromeres and kinetochore proteins that co-cluster away from the condensed chromosomes...
May 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28559969/escape-of-u251-glioma-cells-from-temozolomide-induced-senescence-was-modulated-by-cdk1-survivin-signaling
#15
Zhenhua Song, Yunyun Pan, Gengqiang Ling, Shiyong Wang, Min Huang, Xiaodan Jiang, Yiquan Ke
Temozolomide (TMZ) has been widely used in conjunction with radiotherapy for treating various types of cancers. However, tumor cells arrested in senescence due to TMZ administration can sometimes escape and become drug resistant. In the current study, the possible role of survivin in the senescence escape of TMZ-treated glioma cells was comprehensively studied. The levels of survivin and CDK1 expression in a human glioma cell line (U251) were monitored, and cell apoptosis, cell cycle distribution, anchorage-independent growth, and senescence were studied in U251 cells in different degrees of senescence...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28555567/control-of-png-kinase-a-key-regulator-of-mrna-translation-is-coupled-to-meiosis-completion-at-egg-activation
#16
Masatoshi Hara, Boryana Petrova, Terry L Orr-Weaver
The oocyte-to-embryo transition involves extensive changes in mRNA translation, regulated in Drosophila by the PNG kinase complex whose activity we show here to be under precise developmental control. Despite presence of the catalytic PNG subunit and the PLU and GNU activating subunits in the mature oocyte, GNU is phosphorylated at Cyclin B/CDK1sites and unable to bind PNG and PLU. In vitro phosphorylation of GNU by CyclinB/CDK1 blocks activation of PNG. Meiotic completion promotes GNU dephosphorylation and PNG kinase activation to regulate translation...
May 30, 2017: ELife
https://www.readbyqxmd.com/read/28549341/cdk1-interacts-with-iaspp-to-regulate-colorectal-cancer-cell-proliferation-through-p53-pathway
#17
Wei Gan, Hua Zhao, Tiegang Li, Kuijie Liu, Jiangsheng Huang
CDK1 (cyclin-dependent kinase 1) is a critical regulator of the G2-M checkpoint. CDK1 is considered a possible target for cancer treatment. In addition to CDK1, iASPP plays essential role in maintaining cancer cell proliferation. In the present study, we monitored the expression of CDK1 and iASPP at mRNA and protein levels in CRC tissues and cell lines; we also predicted that iASPP protein might interact with CDK1 protein. By performing GST pull-down assay and Co-IP assay, we confirmed the interaction of CDK1 and iASPP protein...
May 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28546431/disruption-of-mitochondrial-electron-transport-chain-function-potentiates-the-pro-apoptotic-effects-of-mapk-inhibition
#18
Andrew P Trotta, Jesse D Gelles, Madhavika N Serasinghe, Patrick Loi, Jack L Arbiser, Jerry E Chipuk
The mitochondrial network is a major site of ATP production through the coupled integration of the electron transport chain (ETC) with oxidative phosphorylation. In melanoma, arising from the Val600Glu mutation in the kinase v-RAF murine sarcoma viral oncogene homolog B (BRAFV600E), oncogenic signaling enhances glucose-dependent metabolism, while reducing mitochondrial ATP production. Likewise, when BRAFV600E is pharmacologically inhibited by targeted therapies (e.g. PLX-4032/Vemurafenib), glucose metabolism is reduced and cells increase mitochondrial ATP production to sustain survival...
May 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28534969/the-cdc2-cdk1-inhibitor-purvalanol-a-enhances-the-cytotoxic-effects-of-taxol-through-op18-stathmin-in-non-small-cell-lung-cancer-cells-in%C3%A2-vitro
#19
Xian Chen, Ying Liao, Dan Long, Ting Yu, Fang Shen, Xuechi Lin
Purvalanol A is a highly selective inhibitor of Cdc2 [also known as cyclin-dependent kinase 1 (CDK1)]. Taxol is an anti-tumor chemotherapeutic drug which is widely used clinically. In this study, the CDK1 inhibitor, purvalanol A was applied to explore the relevance of Cdc2 signaling and taxol sensitivity through analyses, such as cellular proliferation and apoptosis assays, ELISA, western blot analysis and immunoprecipitation. We demonstrated that purvalanol A effectively enhanced the taxol-induced apoptosis of NCI-H1299 cells, as well as its inhibitory effects on cellular proliferation and colony formation...
May 15, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28521470/new-role-of-human-ribosomal-protein-s3-regulation-of-cell-cycle-via-phosphorylation-by-cyclin-dependent-kinase-2
#20
Se Hee Han, Ji Hyung Chung, Joon Kim, Key-Sun Kim, Ye Sun Han
Human ribosomal protein S3 (hRpS3) is a component of the 40S ribosomal subunit that associated in protein synthesis. hRpS3 has additional ribosomal functions such as DNA repair, transcription, metastasis, and apoptosis via interaction with numerous signaling molecules and has different modifications. Cyclin-dependent kinases (CDKs) are heterodimeric serine/threonine protein kinases that regulate cell cycle progression. Among its members, the Cdk1-cyclin B complex is known to control cell progression in the G2/M phase, while Cdk2-cyclin E/A complexes function in G1/S and S/G2 transition...
May 2017: Oncology Letters
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