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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
#1
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
#2
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
https://www.readbyqxmd.com/read/28504190/expression-and-alternative-splicing-of-the-cyclin-dependent-kinase-inhibitor-3-gene-in-human-cancer
#3
W Douglas Cress, Peng Yu, Jie Wu
The cyclin-dependent kinase inhibitor-3 (CDKN3) gene encodes a dual-specificity protein tyrosine phosphatase that dephosphorylates CDK1/CDK2 and other proteins. CDKN3 is often overexpressed in human cancer, and this overexpression correlates with reduced survival in several types of cancer. CDKN3 transcript variants and mutations have also been reported. The mechanism of CDKN3 overexpression and the role of CDKN3 transcript variants in human cancer are not entirely clear. Here, we review the literature and provide additional data to assess the correlation of CDKN3 expression with patient survival...
May 11, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28502659/apc-c-cdh1-enables-removal-of-shugoshin-2-from-the-arms-of-bivalent-chromosomes-by-moderating-cyclin-dependent-kinase-activity
#4
Ahmed Rattani, Randy Ballesteros Mejia, Katherine Roberts, Maurici B Roig, Jonathan Godwin, Michael Hopkins, Manuel Eguren, Luis Sanchez-Pulido, Elwy Okaz, Sugako Ogushi, Magda Wolna, Jean Metson, Alberto M Pendás, Marcos Malumbres, Béla Novák, Mary Herbert, Kim Nasmyth
In mammalian females, germ cells remain arrested as primordial follicles. Resumption of meiosis is heralded by germinal vesicle breakdown, condensation of chromosomes, and their eventual alignment on metaphase plates. At the first meiotic division, anaphase-promoting complex/cyclosome associated with Cdc20 (APC/C(Cdc20)) activates separase and thereby destroys cohesion along chromosome arms. Because cohesion around centromeres is protected by shugoshin-2, sister chromatids remain attached through centromeric/pericentromeric cohesin...
May 22, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28487562/protein-phosphatase-2a-pp2a-regulates-eg5-to-control-mitotic-progression
#5
Yang Liu, Zhong Zhang, Hui Liang, Xuyang Zhao, Ling Liang, Guangxi Wang, Jingyi Yang, Yan Jin, Michael A McNutt, Yuxin Yin
EG5 (KIF11) is a member of the kinesin-like protein family involved in centrosome separation and bipolar spindle formation. When a cell enters mitosis, CDK1 phosphorylates EG5 at Thr926 and promotes EG5 localization on the mitotic spindle which drives bipolar spindle formation. EG5 provides power for spindle movement and thus controls the dynamics of spindle assembly. However, little is known about EG5 regulation or how EG5 detaches from the spindle upon mitotic exit. In this study we identify EG5 as a novel substrate of PP2A phosphatase, and we show that the PP2A/B55α complex plays an important role in mitotic exit by a mechanism involving EG5...
May 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28486948/associating-transcriptional-modules-with-colon-cancer-survival-through-weighted-gene-co-expression-network-analysis
#6
Rong Liu, Wei Zhang, Zhao-Qian Liu, Hong-Hao Zhou
BACKGROUND: Colon cancer (CC) is a heterogeneous disease influenced by complex gene networks. As such, the relationship between networks and CC should be elucidated to obtain further insights into tumour biology. RESULTS: Weighted gene co-expression network analysis, a powerful technique used to extract co-expressed gene networks from mRNA expressions, was conducted to identify 11 co-regulated modules in a discovery dataset with 461 patients. A transcriptional module enriched in cell cycle processes was correlated with the recurrence-free survival of the CC patients in the discovery (HR = 0...
May 9, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28486050/the-cdk4-6-inhibitor-palbociclib-synergizes-with-irinotecan-to-promote-colorectal-cancer-cell-death-under-hypoxia
#7
Jun Zhang, Lanlan Zhou, Shuai Zhao, David T Dicker, Wafik S El-Deiry
Hypoxia is an inherent impediment to cancer therapy. Palbociclib, a highly selective inhibitor for CDK4/6, has been tested in numerous clinical trials and has been approved by the FDA. We previously reported that CDK inhibitors can destabilize HIF1α regardless of the presence of hypoxia and can sensitize tumor cells to TRAIL through dual blockade of CDK1 and GSK3-β. In order to translate this knowledge into a cancer therapeutic strategy, we investigated the therapeutic effects and molecular mechanisms of CDK inhibition against colon cancer cells under normoxia and hypoxia...
May 9, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28479321/ska3-phosphorylated-by-cdk1-binds-ndc80-and-recruits-ska-to-kinetochores-to-promote-mitotic-progression
#8
Qian Zhang, Sushama Sivakumar, Yujue Chen, Haishan Gao, Lu Yang, Zhu Yuan, Hongtao Yu, Hong Liu
The spindle and kinetochore-associated (Ska) protein complex is required for accurate chromosome segregation during mitosis [1-6] and consists of two copies each of Ska1, Ska2, and Ska3 proteins [4, 7]. The Ska complex contains multiple microtubule-binding elements and promotes kinetochore-microtubule attachment [8-11]. The Ska1 C-terminal domain (CTD) recruits protein phosphatase 1 (PP1) to kinetochores to promote timely anaphase onset [12]. The Ska complex regulates, and is regulated by, Aurora B [13]. Aurora B phosphorylates both Ska1 and Ska3 to inhibit the kinetochore localization of the Ska complex [14]...
May 22, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28469796/low-dose-radiation-modulates-human-mesenchymal-stem-cell-proliferation-through-regulating-cdk-and-rb
#9
Lei Yang, Ziling Liu, Chen Chen, Xiaofeng Cong, Zhi Li, Shasha Zhao, Meng Ren
Low-dose radiation (LDR) has been known to stimulate cell proliferation. The effect of LDR on human bone marrow mesenchymal stem cells (BMSCs), however, remains to be determined. The current study, therefore, aimed to investigate the effect of LDR on human BMSC proliferation and its mechanisms. To accomplish this, human BMSCs were isolated from ribs and cultured with or without exposition to LDR (75 mGy) for 24 h. Cell proliferation was assessed by MTT assay, the cytokines secreted by the BMSCs were quantified by ELISA, and the proteins associated with cell proliferation and cell cycle were evaluated by immunoblot analysis...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28465438/human-phosphatase-cdc14a-regulates-actin-organization-through-dephosphorylation-of-epithelial-protein-lost-in-neoplasm
#10
Nan-Peng Chen, Borhan Uddin, Robert Hardt, Wen Ding, Marko Panic, Ilaria Lucibello, Patricia Kammerer, Thomas Ruppert, Elmar Schiebel
CDC14 is an essential dual-specificity phosphatase that counteracts CDK1 activity during anaphase to promote mitotic exit in Saccharomyces cerevisiae Surprisingly, human CDC14A is not essential for cell cycle progression. Instead, it regulates cell migration and cell adhesion. Little is known about the substrates of hCDC14A and the counteracting kinases. Here, we combine phospho-proteome profiling and proximity-dependent biotin identification to identify hCDC14A substrates. Among these targets were actin regulators, including the tumor suppressor eplin...
May 2, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28463034/altered-mirna-expression-in-aniline-mediated-cell-cycle-progression-in-rat-spleen
#11
Gangduo Wang, Jianling Wang, M Firoze Khan
Aniline exposure is associated with toxicity to the spleen, however, early molecular events in aniline-induced cell cycle progression in the spleen remain unknown. miRNAs have been implicated in tumor development by modulating key cell cycle regulators and controlling cell proliferation. This study was, therefore, undertaken on the expression of miRNAs, regulation of cyclins and cyclin-dependent kinases (CDKs) in an experimental condition that precedes a tumorigenic response. Male SD rats were treated with aniline (1 mmol/kg/day by gavage) for 7 days, and expression of miRNAs, cyclins and CDKs in rat spleens were analyzed...
May 2, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28461508/conditional-knockin-of-dnmt3a-r878h-initiates-acute-myeloid-leukemia-with-mtor-pathway-involvement
#12
Yu-Jun Dai, Yue-Ying Wang, Jin-Yan Huang, Li Xia, Xiao-Dong Shi, Jie Xu, Jing Lu, Xian-Bin Su, Ying Yang, Wei-Na Zhang, Pan-Pan Wang, Song-Fang Wu, Ting Huang, Jian-Qing Mi, Ze-Guang Han, Zhu Chen, Sai-Juan Chen
DNMT3A is frequently mutated in acute myeloid leukemia (AML). To explore the features of human AML with the hotspot DNMT3A R882H mutation, we generated Dnmt3a R878H conditional knockin mice, which developed AML with enlarged Lin(-)Sca1(+)cKit(+) cell compartments. The transcriptome and DNA methylation profiling of bulk leukemic cells and the single-cell RNA sequencing of leukemic stem/progenitor cells revealed significant changes in gene expression and epigenetic regulatory patterns that cause differentiation arrest and growth advantage...
May 1, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28455557/three-cdk1-sites-in-the-kinesin-5-cin8-catalytic-domain-coordinate-motor-localization-and-activity-during-anaphase
#13
Alina Goldstein, Nurit Siegler, Darya Goldman, Haim Judah, Ervin Valk, Mardo Kõivomägi, Mart Loog, Larisa Gheber
The bipolar kinesin-5 motors perform essential functions in mitotic spindle dynamics. We previously demonstrated that phosphorylation of at least one of the Cdk1 sites in the catalytic domain of the Saccharomyces cerevisiae kinesin-5 Cin8 (S277, T285, S493) regulates its localization to the anaphase spindle. The contribution of these three sites to phospho-regulation of Cin8, as well as the timing of such contributions, remains unknown. Here, we examined the function and spindle localization of phospho-deficient (serine/threonine to alanine) and phospho-mimic (serine/threonine to aspartic acid) Cin8 mutants...
April 28, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28446681/minute-virus-of-mice-mvm-inhibits-transcription-of-the-cyclin-b1-gene-during-infection
#14
Matthew S Fuller, Kinjal Majumder, David J Pintel
Replication of minute virus of mice (MVM) induces a sustained cellular DNA damage response (DDR) which the virus then exploits to prepare the nuclear environment for effective parvovirus takeover. An essential aspect of the MVM-induced DDR is the establishment of a potent pre-mitotic block, which we previously found to be independent of activated p21 and ATR/Chk1 signaling. This arrest, unlike others previously reported, depends upon the significant, specific depletion of cyclin B1 and its encoding RNA, which precludes cyclin B1/CDK1 complex function thus preventing mitotic entry...
April 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28446604/cell-cycle-dependent-regulation-of-greatwall-kinase-by-protein-phosphatase-1-and-regulatory-subunit-3b
#15
Dapeng Ren, Laura A Fisher, Jing Zhao, Ling Wang, Byron C Williams, Michael L Goldberg, Aimin Peng
Greatwall (Gwl) kinase plays an essential role in regulation of mitotic entry and progression. Mitotic activation of Gwl requires both cyclin-dependent kinase 1 (CDK1)-dependent phosphorylation and its autophosphorylation at an evolutionarily-conserved serine residue near the carboxyl-terminus (Ser-883 in Xenopus). In this study we show that Gwl associates with protein phosphatase 1 (PP1), particularly PP1γ, which mediates the dephosphorylation of Gwl Ser-883. Consistent with the mitotic activation of Gwl, its association with PP1 is disrupted in mitotic cells and egg extracts...
April 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28434945/prognostic-biomarker-identification-through-integrating-the-gene-signatures-of-hepatocellular-carcinoma-properties
#16
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
#17
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
#18
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
#19
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
#20
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
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