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https://www.readbyqxmd.com/read/29452922/structural-biology-of-the-separase-securin-complex-with-crucial-roles-in-chromosome-segregation
#1
REVIEW
Shukun Luo, Liang Tong
The cysteine protease separase opens the cohesin ring by cleaving its kleisin subunit and is a pivotal cell cycle factor for the transition from metaphase to anaphase. It is inhibited by forming a complex with the chaperone securin, and in vertebrates, also by the Cdk1-cyclin B1 complex. Separase is activated upon the destruction of securin or cyclin B1 by the proteasome, after ubiquitination by the anaphase-promoting complex/cyclosome (APC/C). Here we review recent structures of the active protease segment of Chaetomium thermophilum separase in complex with a substrate-mimic inhibitor and full-length Saccharomyces cerevisiae and Caenorhabditis elegans separase in complex with securin...
February 13, 2018: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/29449348/mitotic-waves-in-the-early-embryogenesis-of-drosophila-bistability-traded-for-speed
#2
Massimo Vergassola, Victoria E Deneke, Stefano Di Talia
Early embryogenesis of most metazoans is characterized by rapid and synchronous cleavage divisions. Chemical waves of Cdk1 activity were previously shown to spread across Drosophila embryos, and the underlying molecular processes were dissected. Here, we present the theory of the physical mechanisms that control Cdk1 waves in Drosophila The in vivo dynamics of Cdk1 are captured by a transiently bistable reaction-diffusion model, where time-dependent reaction terms account for the growing level of cyclins and Cdk1 activation across the cell cycle...
February 15, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29444369/rotaviral-non-structural-protein-4-triggers-dynamin-related-protein-1-dependent-mitochondrial-fragmentation-during-infection
#3
Arpita Mukherjee, Upayan Patra, Rahul Bhowmick, Mamta Chawla-Sarkar
Dynamic equilibrium between mitochondrial fission and mitochondrial fusion serves as an important quality control system within cells ensuring cellular vitality and homeostasis. Viruses often target mitochondrial dynamics as a part of their obligatory cellular reprogramming. The present study was undertaken to assess the status and regulation of mitochondrial dynamics during rotavirus (RV) infection. Distinct fragmentation of mitochondrial syncytia was observed during late hours of RV (SA11, Wa, A5-13) infection...
February 14, 2018: Cellular Microbiology
https://www.readbyqxmd.com/read/29438989/mitotic-phosphorylation-of-senp3-regulates-de-sumoylation-of-chromosome-associated-proteins-and-chromosome-stability
#4
Bo Wei, Chao Huang, Bin Liu, Yang Wang, Nansong Xia, Qiuju Fan, Guo-Qiang Chen, Jinke Cheng
Progression of mitotic cell cycle as well as chromosome condensation and segregation are controlled by posttranslational protein modifications such as phosphorylation and SUMOylation. However, how SUMO isopeptidases (SENP) regulate cell mitotic procession is largely unknown. Here we demonstrate that precise phosphorylation of SENP3 during mitosis suppresses SENP3 de-SUMOylation activity towards chromosome-associated proteins including Topoisomerase IIα (Topo IIα). Cyclin B-dependent kinases 1 (CDK1) and protein phosphatase 1α (PP1α) were identified as the kinase and phosphatase in control of mitotic SENP3 phosphorylation, respectively...
February 8, 2018: Cancer Research
https://www.readbyqxmd.com/read/29438360/an-rnai-based-screen-reveals-plk1-cdk1-and-ndc80-as-potential-therapeutic-targets-in-malignant-pleural-mesothelioma
#5
A Linton, Y Y Cheng, K Griggs, L Schedlich, M B Kirschner, S Gattani, S Srikaran, S Chuan-Hao Kao, B C McCaughan, S Klebe, N van Zandwijk, G Reid
This corrects the article DOI: 10.1038/bjc.2013.731.
February 13, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29435156/cis-trimethoxy-resveratrol-induces-intrinsic-apoptosis-via-prometaphase-arrest-and-prolonged-cdk1-activation-pathway-in-human-jurkat-t-cells
#6
Chae Eun Kim, Do Youn Jun, Jong-Sik Kim, Young Ho Kim
Cis-trimethoxy resveratrol (cis-3M-RES) induced dose-dependent cytotoxicity and apoptotic DNA fragmentation in Jurkat T cell clones (JT/Neo); however, it induced only cytostasis in BCL-2-overexpressing cells (JT/BCL-2). Treatment with 0.25 μM cis-3M-RES induced G2/M arrest, BAK activation, Δψm loss, caspase-9 and caspase-3 activation, and poly (ADP-ribose) polymerase (PARP) cleavage in JT/Neo cells time-dependently but did not induce these events, except G2/M arrest, in JT/BCL-2 cells. Moreover, cis-3M-RES induced CDK1 activation, BCL-2 phosphorylation at Ser-70, MCL-1 phosphorylation at Ser-159/Thr-163, and BIM (BIMEL and BIML) phosphorylation irrespective of BCL-2 overexpression...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29435009/karyopherin-subunit-%C3%AE-2-expression-accelerates-cell-cycle-progression-by-upregulating-ccnb2-and-cdk1-in-hepatocellular-carcinoma
#7
Chun-Lin Gao, Gao-Wei Wang, Guan-Qin Yang, Hong Yang, Li Zhuang
Different types of cancer exhibit distinct gene expression profiles. The present study aimed to identify a specific gene dysregulated in hepatocellular carcinoma (HCC) that was essential for cancer progression. The whole transcriptomes of primary HCC tissue samples were analyzed with microarrays. The most significantly differentially expressed gene was identified, specifically karyopherin subunit-α 2 (KPNA2), and an analysis using the Oncomine online tool was performed with data from The Cancer Genome Atlas to predict associated genes in HCC...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29434861/bioinformatic-analysis-of-gene-expression-profiles-of-pituitary-gonadotroph-adenomas
#8
Ziming Hou, Jun Yang, Gang Wang, Changjiang Wang, Hongbing Zhang
The aim of the present study was to identify genes, microRNAs (miRNAs/miRs) or pathways associated with the development of pituitary gonadotroph adenomas. The array data of GSE23207, which included 16 samples of multiple endocrine neoplasia-associated rat pituitary homozygous mutations and 5 pituitary tissue samples from healthy rats, were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were analyzed prior to functional enrichment analysis and protein-protein interaction (PPI) network construction...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29433585/characterization-and-validation-of-potential-therapeutic-targets-based-on-the-molecular-signature-of-patient-derived-xenografts-in-gastric-cancer
#9
Zuhua Chen, Wenwen Huang, Tiantian Tian, Wanchun Zang, Jingyuan Wang, Zhentao Liu, Zhongwu Li, Yumei Lai, Zhi Jiang, Jing Gao, Lin Shen
BACKGROUND: Patient-derived xenograft (PDX) models with definite molecular signature are attractive preclinical models for development of novel targeted drugs. Here, we profiled and explored potential therapeutic targets based on characterized PDX models for advanced gastric cancer (AGC). METHODS: The genomic variation and molecular profile of 50 PDX models from AGC patients were analyzed by targeted next-generation sequencing, in situ hybridization, and immunohistochemistry...
February 13, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29432993/oridonin-inhibits-oral-cancer-growth-and-pi3k-akt-signaling-pathway
#10
Jing Yang, Xianyue Ren, Liping Zhang, Yuanyuan Li, Bin Cheng, Juan Xia
Oridonin, a bioactive diterpenoid purified from Rabdosia rubescens, has been shown to possess anticancer capacity in several cancer types. However, its effects on oral squamous cell carcinoma (OSCC) cells remain unclear. This study aimed to investigate the anticancer ability of oridonin in OSCC cells, including proliferation, apoptosis and underlying mechanisms using the OSCC cell lines, UM1 and SCC25. The results showed that oridonin not only inhibited proliferation and clonal formation but also induced G2/M cell cycle arrest and apoptosis in UM1 and SCC25 cells in a dose-dependent manner...
February 9, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29429832/design-and-synthesis-of-4-2-3-dihydro-1h-benzo-d-pyrrolo-1-2-a-imidazol-7-yl-n-5-piperazin-1-ylmethyl-pyridine-2-yl-pyrimidin-2-amine-as-a-highly-potent-and-selective-cyclin-dependent-kinases-4-and-6-inhibitors-and-the-discovery-of-structure-activity-relationships
#11
Yan Wang, Wen-Jian Liu, Lei Yin, Heng Li, Zhen-Hua Chen, Dian-Xi Zhu, Xiu-Qing Song, Zhen-Zhen Cheng, Peng Song, Zhan Wang, Zhi-Gang Li
Cyclin-dependent kinases 4/6 play an important role in regulation of cell cycle, and overexpress in a variety of cancers. Up to now, new CDK inhibitors still need to be developed due to its poor selectivity. Herein we report a novel series of 4-(2,3-dihydro-1H-benzo[d]pyrrolo[1,2-a]imidazole-7-yl)-N-(5-(piperazin-1-ylmethyl)pyridine-2-yl)pyrimidin-2-amine anologues as potent CDK 4/6 inhibitors based on LY2835219 (Abemaciclib). Compound 10d, which exhibits approximate potency on CDK4/6 (IC50 = 7.4/0.9 nM), has both good pharmacokinetic characters and high selectivity on CDK1 compared with LY2835219...
January 31, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29428472/a-novel-harmine-derivative-n-4-hydroxycarbamoyl-benzyl-1-4-methoxyphenyl-9h-pyrido-3-4-b-indole-3-carboxamide-hbc-as-histone-deacetylase-inhibitor-in-vitro-antiproliferation-apoptosis-induction-cell-cycle-arrest-and-antimetastatic-effects
#12
Jie-Fei Miao, Yan-Fu Peng, Shi Chen, Wei-Jie Gao, Qiu-Xing Yang, Peng Zhu, Jing Guo, Jinhua Tao, Lin Luo, Yanan Zhang, Yong Ling
This study aims to design and synthesize a novel harmine derivative N-(4-(hydroxycarbamoyl) benzyl)-1-(4-methoxyphenyl)-9H-pyrido [3,4-b]indole-3-carboxamide (HBC) as histone deacetylase (HDAC) inhibitor, and evaluate its antitumor activities and anti-metastasis mechanism. HBC not only exerted significant ant-proliferation activity against five human cancer cell lines, especially for HepG2 cell with an IC50 value of 2.21μM, which is nearly three-fold lower than SAHA (IC50 = 6.26µM), but also showed selective HDAC1/6 inhibitory effects in vitro...
February 8, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29424068/mutations-at-multiple-cdk-phosphorylation-consensus-sites-on-cdt2-increase-the-affinity-of-crl4cdt2-for-pcna-and-its-ubiquitination-activity-in-s-phase
#13
Kohei Nukina, Akiyo Hayashi, Yasushi Shiomi, Kaoru Sugasawa, Motoaki Ohtsubo, Hideo Nishitani
CRL4Cdt2 ubiquitin ligase plays an important role maintaining genome integrity during the cell cycle. A recent report suggested that Cdk1 negatively regulates CRL4Cdt2 activity through phosphorylation of its receptor, Cdt2, but the involvement of phosphorylation remains unclear. To address this, we mutated all CDK consensus phosphorylation sites located in the C-terminal half region of Cdt2 (Cdt2-18A) and examined the effect on substrate degradation. We show that both cyclinA/Cdk2 and cyclinB/Cdk1 phosphorylated Cdt2 in vitro and that phosphorylation was reduced by the 18A mutation both in vitro and in vivo...
February 9, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/29422626/protein-interactomes-of-protein-phosphatase-2a-b55-regulatory-subunits-reveal-b55-mediated-regulation-of-replication-protein-a-under-replication-stress
#14
Feifei Wang, Songli Zhu, Laura A Fisher, Weidong Wang, Gregory G Oakley, Chunling Li, Aimin Peng
The specific function of PP2A, a major serine/threonine phosphatase, is mediated by regulatory targeting subunits, such as members of the B55 family. Although implicated in cell division and other pathways, the specific substrates and functions of B55 targeting subunits are largely undefined. In this study we identified over 100 binding proteins of B55α and B55β in Xenopus egg extracts that are involved in metabolism, mitochondria function, molecular trafficking, cell division, cytoskeleton, DNA replication, DNA repair, and cell signaling...
February 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29420299/phosphorylation-of-arhgap19-by-cdk1-and-rock-regulates-its-subcellular-localization-and-function-during-mitosis
#15
Claire Marceaux, Dominique Petit, Jacques Bertoglio, Muriel D David
ARHGAP19 is a hematopoietic-specific RhoGAP that acts through the RhoA/ROCK pathway to critically regulate cell elongation and cytokinesis during lymphocyte mitosis. We report here that during mitosis progression, ARHGAP19 is sequentially phosphorylated by the RhoA-activated kinase ROCK on serine residue 422 and by CDK1 on threonine residues 404 and 476. The phosphorylation of ARHGAP19 by ROCK occurs before mitosis onset and generates a binding site for 14-3-3 family proteins. ARHGAP19 is then phosphorylated by CDK1 in prometaphase...
February 2, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29419418/correction-control-of-cdc6-accumulation-by-cdk1-and-mapk-is-essential-for-completion-of-oocyte-meiotic-divisions-in%C3%A2-xenopus-doi-10-1242-jcs-166553
#16
Enrico M Daldello, Tran Le, Robert Poulhe, Catherine Jessus, Olivier Haccard, Aude Dupré
No abstract text is available yet for this article.
February 1, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29416675/phosphorylation-of-caspase-9-at-thr125-directs-paclitaxel-resistance-in-ovarian-cancer
#17
Mi Ran Byun, Jin Woo Choi
Although paclitaxel is routinely prescribed for the treatment of epithelial ovarian cancer (EOC), paclitaxel resistance is common in EOC and correlates with short survival of patients. A previous pharmacogenomic study revealed the importance of cyclin-dependent kinase 1 (CDK1) activity in a response on paclitaxel. However, a subsequent research showed that the expression level of CDK1 failed to show significant correlation with delayed apoptosis and patient survival. Rather, the expression and phosphorylation of capase-9, the downstream target molecule of CDK1, appeared to determine drug resistance...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29416627/transcriptome-evolution-from-breast-epithelial-cells-to-basal-like-tumors
#18
Gabriel Santpere, Ana Alcaráz-Sanabria, Verónica Corrales-Sánchez, Atanasio Pandiella, Balázs Győrffy, Alberto Ocaña
In breast cancer, it is unclear the functional modifications at a transcriptomic level that are associated with the evolution from epithelial cells and ductal carcinoma in situ (DCIS) to basal-like tumors. By applying weighted gene co-expression network analysis (WGCNA), we identified 17 gene co-expression modules in normal, DCIS and basal-like tumor samples. We then correlated the expression pattern of these gene modules with disease progression from normal to basal-like tumours and found eight modules exhibiting a high and statistically significant correlation...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29416014/lncrna-nck1-as1-promotes-proliferation-and-induces-cell-cycle-progression-by-crosstalk-nck1-as1-mir-6857-cdk1-pathway
#19
Haiyu Li, Yongqin Jia, Junning Cheng, Geli Liu, Fangzhou Song
The purpose of this study was to develop an lncRNA signature to improve the prediction of the prognosis of cervical cancer through integration bioinformatics and analysis of TCGA RNA sequencing data. In this study, we established a set of four lncRNA signatures that was significantly associated with recurrence-free survival using the Cox regression model. Functionally, we screened the CC-associated lncRNA NCK1-AS1 as a new candidate lncRNA and regulator which promotes development and progression in CC. qRT-PCR and RNA in situ hybridization (RISH) results showed that NCK1-AS1 was significantly up-regulated in 77...
February 7, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29414815/lncrna-gas5-represses-osteosarcoma-cells-growth-and-metastasis-via-sponging-mir-203a
#20
Yang Wang, Daliang Kong
BACKGROUND/AIMS: LncRNA GAS5, a growth suppressor, has been reported to exert anti-tumor actions in various cancers, whereas the exact mechanism underling the anti-tumor action is still unclear. This study was aimed to investigate the effect of lncRNA GAS5 on osteosarcoma and tried to decode the underling mechanisms. METHODS: Expressions of lncRNA GAS5 in MG-63 cells were silenced by shRNA transfection, while were overexpressed by vector transfection. Cell viability, migration, invasion and apoptosis were respectively assessed by MTT, Transwell assay and flow cytometry...
January 31, 2018: Cellular Physiology and Biochemistry
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