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https://www.readbyqxmd.com/read/29149186/cell-cycle-time-series-gene-expression-data-encoded-as-cyclic-attractors-in-hopfield-systems
#1
Anthony Szedlak, Spencer Sims, Nicholas Smith, Giovanni Paternostro, Carlo Piermarocchi
Modern time series gene expression and other omics data sets have enabled unprecedented resolution of the dynamics of cellular processes such as cell cycle and response to pharmaceutical compounds. In anticipation of the proliferation of time series data sets in the near future, we use the Hopfield model, a recurrent neural network based on spin glasses, to model the dynamics of cell cycle in HeLa (human cervical cancer) and S. cerevisiae cells. We study some of the rich dynamical properties of these cyclic Hopfield systems, including the ability of populations of simulated cells to recreate experimental expression data and the effects of noise on the dynamics...
November 17, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/29142107/is-inflammatory-micronucleation-the-key-to-a-successful-anti-mitotic-cancer-drug
#2
REVIEW
T J Mitchison, J Pineda, J Shi, S Florian
Paclitaxel is a successful anti-cancer drug that kills cancer cells in two-dimensional culture through perturbation of mitosis, but whether it causes tumour regression by anti-mitotic actions is controversial. Drug candidates that specifically target mitosis, including inhibitors of kinesin-5, AurkA, AurkB and Plk1, disappointed in the clinic. Current explanations for this discrepancy include pharmacokinetic differences and hypothetical interphase actions of paclitaxel. Here, we discuss post-mitotic micronucleation as a special activity of taxanes that might explain their higher activity in solid tumours...
November 2017: Open Biology
https://www.readbyqxmd.com/read/29129717/a-chemoproteomic-approach-to-query-the-degradable-kinome-using-a-multi-kinase-degrader
#3
Hai-Tsang Huang, Dennis Dobrovolsky, Joshiawa Paulk, Guang Yang, Ellen L Weisberg, Zainab M Doctor, Dennis L Buckley, Joong-Heui Cho, Eunhwa Ko, Jaebong Jang, Kun Shi, Hwan Geun Choi, James D Griffin, Ying Li, Steven P Treon, Eric S Fischer, James E Bradner, Li Tan, Nathanael S Gray
Heterobifunctional molecules that recruit E3 ubiquitin ligases, such as cereblon, for targeted protein degradation represent an emerging pharmacological strategy. A major unanswered question is how generally applicable this strategy is to all protein targets. In this study, we designed a multi-kinase degrader by conjugating a highly promiscuous kinase inhibitor with a cereblon-binding ligand, and used quantitative proteomics to discover 28 kinases, including BTK, PTK2, PTK2B, FLT3, AURKA, AURKB, TEC, ULK1, ITK, and nine members of the CDK family, as degradable...
November 7, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/29050234/a-small-molecule-inhibitor-targeting-the-aurkc-i%C3%AE%C2%BAb%C3%AE-interaction-decreases-transformed-growth-of-mda-mb-231-breast-cancer-cells
#4
Eun Hee Han, Jin-Young Min, Shin-Ae Yoo, Sung-Joon Park, Yun-Jeong Choe, Hee Sub Yun, Zee-Won Lee, Sun Woo Jin, Hyung Gyun Kim, Hye Gwang Jeong, Hyun Kyoung Kim, Nam Doo Kim, Young-Ho Chung
The Aurora kinases, Aurora A (AURKA), Aurora B (AURKB), and Aurora C (AURKC), are serine/threonine kinases required for the control of mitosis (AURKA and AURKB) or meiosis (AURKC). Several Aurora kinase inhibitors are being investigated as novel anticancer therapeutics. Recent studies demonstrated that AURKC activation contributes to breast cancer cell transformation. Therefore, AURKC is both a promising marker and therapeutic target for breast cancer; however, its signaling network has not been fully characterized...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29040668/aurora-kinase-b-a-novel-regulator-of-terf1-binding-and-telomeric-integrity
#5
Foong Lyn Chan, Benjamin Vinod, Karel Novy, Ralf B Schittenhelm, Cheng Huang, Maheshi Udugama, Juan Nunez-Iglesias, Jane I Lin, Linda Hii, Julie Chan, Hilda A Pickett, Roger J Daly, Lee H Wong
AURKB (Aurora Kinase B) is a serine/threonine kinase better known for its role at the mitotic kinetochore during chromosome segregation. Here, we demonstrate that AURKB localizes to the telomeres in mouse embryonic stem cells, where it interacts with the essential telomere protein TERF1. Loss of AURKB function affects TERF1 telomere binding and results in aberrant telomere structure. In vitro kinase experiments successfully identified Serine 404 on TERF1 as a putative AURKB target site. Importantly, in vivo overexpression of S404-TERF1 mutants results in fragile telomere formation...
October 10, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29025594/gene-expression-profiling-pathway-analysis-and-subtype-classification-reveal-molecular-heterogeneity-in-hepatocellular-carcinoma-and-suggest-subtype-specific-therapeutic-targets
#6
Rahul Agarwal, Jitendra Narayan, Amitava Bhattacharyya, Mayank Saraswat, Anil Kumar Tomar
A very low 5-year survival rate among hepatocellular carcinoma (HCC) patients is mainly due to lack of early stage diagnosis, distant metastasis and high risk of postoperative recurrence. Hence ascertaining novel biomarkers for early diagnosis and patient specific therapeutics is crucial and urgent. Here, we have performed a comprehensive analysis of the expression data of 423 HCC patients (373 tumors and 50 controls) downloaded from The Cancer Genome Atlas (TCGA) followed by pathway enrichment by gene ontology annotations, subtype classification and overall survival analysis...
October 2017: Cancer Genetics
https://www.readbyqxmd.com/read/28977903/polymorphisms-in-mitotic-checkpoint-related-genes-can-influence-survival-outcomes-of-early-stage-non-small-cell-lung-cancer
#7
Hyo Gyoung Kang, Seung Soo Yoo, Jin Eun Choi, Mi Jeong Hong, Sook Kyung Do, Cheng Cheng Jin, Soyoun Kim, Won Kee Lee, Sun Ha Choi, So Yeon Lee, Hyun Jung Kim, Shin Yup Lee, Jaehee Lee, Seung Ick Cha, Chang Ho Kim, Yangki Seok, Eungbae Lee, Sukki Cho, Sanghoon Jheon, Jae Yong Park
This study was conducted to investigate the association between variants in mitotic checkpoint-related genes and clinical outcomes of non-small cell lung cancer (NSCLC). A total of 766 patients with NSCLC who underwent curative surgery were enrolled. Among the 73 variants evaluated, 4 variants were related with survival outcomes. BUB3 rs7897156C>T was associated with worse overall survival under a recessive model (adjusted hazard ratio = 1.58, 95% confidence interval = 1.07-2.33, P = 0.02). AURKB rs1059476G>A was associated with better overall survival under a recessive model (adjusted hazard ratio = 0...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28843004/single-nucleotide-polymorphisms-rs911160-in-aurka-and-rs2289590-in-aurkb-mitotic-checkpoint-genes-contribute-to-gastric-cancer-susceptibility
#8
Aner Mesic, Ela Markocic, Marija Rogar, Robert Juvan, Petra Hudler, Radovan Komel
BACKGROUND: Single nucleotide polymorphisms (SNPs) in mitotic checkpoint genes could confer increased susceptibility to gastric cancer (GC). We investigated the association of Aurora kinase A (AURKA), Aurora kinase B (AURKB), Aurora kinase C (AURKC), Polo-like kinase 1 (PLK1) and Budding uninhibited by benzimidazol 3, yeast (BUB3) gene polymorphisms with GC risk. MATERIALS AND METHODS: Genotyping of 6 SNPs in AURKA (rs911160 and rs8173), AURKB (rs2289590), AURKC (rs11084490), PLK1 (rs42873), and BUB3 (rs7897156) was performed using TaqMan genotyping assays...
August 26, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28733545/a-small-molecule-inhibitor-targeting-the-aurkc-i%C3%AE%C2%BAb%C3%AE-interaction-decreases-transformed-growth-of-mda-mb-231-breast-cancer-cells
#9
Eun Hee Han, Jin-Young Min, Shin-Ae Yoo, Sung-Joon Park, Yun-Jeong Choe, Hee Sub Yun, Zee-Won Lee, Sun Woo Jin, Hyung Gyun Kim, Hye Gwang Jeong, Hyun Kyoung Kim, Nam Doo Kim, Young-Ho Chung
The Aurora kinases, Aurora A (AURKA), Aurora B (AURKB), and Aurora C (AURKC), are serine/threonine kinases required for the control of mitosis (AURKA and AURKB) or meiosis (AURKC). Several Aurora kinase inhibitors are being investigated as novel anticancer therapeutics. Recent studies demonstrated that AURKC activation contributes to breast cancer cell transformation. Therefore, AURKC is both a promising marker and therapeutic target for breast cancer; however, its signaling network has not been fully characterized...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28700337/polymorphisms-in-mitotic-checkpoint-related-genes-can-influence-survival-outcomes-of-early-stage-non-small-cell-lung-cancer
#10
Hyo-Gyoung Kang, Seung Soo Yoo, Jin Eun Choi, Mi Jeong Hong, Sook Kyung Do, Cheng Cheng Jin, Soyoun Kim, Won Kee Lee, Sun Ha Choi, So Yeon Lee, Hyun Jung Kim, Shin Yup Lee, Jaehee Lee, Seung Ick Cha, Chang Ho Kim, Yangki Seok, Eungbae Lee, Sukki Cho, Sanghoon Jheon, Jae Yong Park
This study was conducted to investigate the association between variants in mitotic checkpoint-related genes and clinical outcomes of non-small cell lung cancer (NSCLC). A total of 766 patients with NSCLC who underwent curative surgery were enrolled. Among the 73 variants evaluated, 4 variants were related with survival outcomes. BUB3 rs7897156C>T was associated with worse overall survival under a recessive model (adjusted hazard ratio = 1.58, 95% confidence interval = 1.07-2.33, P = 0.02). AURKB rs1059476G>A was associated with better overall survival under a recessive model (adjusted hazard ratio = 0...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28659416/haspin-inhibition-reveals-functional-differences-of-interchromatid-axis-localized-aurkb-and-aurkc
#11
Suzanne M Quartuccio, Shweta S Dipali, Karen Schindler
Aneuploidy is the leading genetic abnormality contributing to infertility, and chromosome segregation errors are common during female mammalian meiosis I (MI). Previous results indicate that haspin kinase regulates resumption of meiosis from prophase arrest, chromosome condensation, and kinetochore-microtubule attachments during early prometaphase of MI. Here we report that haspin inhibition in late prometaphase I causes acceleration of MI, bypass of the spindle assembly checkpoint (SAC), and loss of interchromatid axis-localized Aurora kinase C...
August 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28600475/dual-inhibition-of-hdac-and-tyrosine-kinase-signaling-pathways-with-cudc-907-inhibits-thyroid-cancer-growth-and-metastases
#12
Shweta Kotian, Lisa Zhang, Myriem Boufraqech, Kelli Gaskins, Sudheer Kumar Gara, Martha Quezado, Naris Nilubol, Electron Kebebew
Purpose: There is currently no standard therapy for anaplastic thyroid cancer (ATC) and poorly differentiated thyroid cancer (PDTC), which account for two-thirds of thyroid cancer-related deaths. Driver mutations in the PI3K/AKT and RAF/RAS/MEK/ERK pathways are common in ATC and PDTC. Histone deacetylases (HDAC) regulate cancer initiation and progression. Our aim was to determine the therapeutic efficacy of simultaneously targeting these pathways in thyroid cancer with a single agent and to evaluate biomarkers of treatment response...
June 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28595628/six3-a-tumor-suppressor-inhibits-astrocytoma-tumorigenesis-by-transcriptional-repression-of-aurka-b
#13
Zhibin Yu, Yingnan Sun, Xiaoling She, Zeyou Wang, Shuai Chen, Zhiyong Deng, Yan Zhang, Qiang Liu, Qing Liu, Chunhua Zhao, Peiyao Li, Changhong Liu, Jianbo Feng, Haijuan Fu, Guiyuan Li, Minghua Wu
BACKGROUND: SIX homeobox 3 (SIX3) is a member of the sine oculis homeobox transcription factor family. It plays a vital role in the nervous system development. Our previous study showed that the SIX3 gene is hypermethylated, and its expression is decreased in astrocytoma, but the role of SIX3 remains unknown. METHODS: Chromatin-immunoprecipitation (ChIP) and luciferase reporter assay were used to confirm the binding of SIX3 to the promoter regions of aurora kinase A (AURKA) and aurora kinase B (AURKB)...
June 8, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28588715/aurka-mrna-expression-is-an-independent-predictor-of-poor-prognosis-in-patients-with-non-small-cell-lung-cancer
#14
Ahmed S K Al-Khafaji, Michael W Marcus, Michael P A Davies, Janet M Risk, Richard J Shaw, John K Field, Triantafillos Liloglou
Deregulation of mitotic spindle genes has been reported to contribute to the development and progression of malignant tumours. The aim of the present study was to explore the association between the expression profiles of Aurora kinases (AURKA, AURKB and AURKC), cytoskeleton-associated protein 5 (CKAP5), discs large-associated protein 5 (DLGAP5), kinesin-like protein 11 (KIF11), microtubule nucleation factor (TPX2), monopolar spindle 1 kinase (TTK), and β-tubulins (TUBB) and (TUBB3) genes and clinicopathological characteristics in human non-small cell lung carcinoma (NSCLC)...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28562334/gene-co-expression-network-reveals-shared-modules-predictive-of-stage-and-grade-in-serous-ovarian-cancers
#15
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...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28434146/differential-regulation-of-h3s10-phosphorylation-mitosis-progression-and-cell-fate-by-aurora-kinase-b-and-c-in-mouse-preimplantation-embryos
#16
Wenzhi Li, Peizhe Wang, Bingjie Zhang, Jing Zhang, Jia Ming, Wei Xie, Jie Na
Coordination of cell division and cell fate is crucial for the successful development of mammalian early embryos. Aurora kinases are evolutionarily conserved serine/threonine kinases and key regulators of mitosis. Aurora kinase B (AurkB) is ubiquitously expressed while Aurora kinase C (AurkC) is specifically expressed in gametes and preimplantation embryos. We found that increasing AurkC level in one blastomere of the 2-cell embryo accelerated cell division and decreasing AurkC level slowed down mitosis. Changing AurkB level had the opposite effect...
April 22, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28404751/chromosomal-passenger-complex-hydrodynamics-suggests-chaperoning-of-the-inactive-state-by-nucleoplasmin-nucleophosmin
#17
Mariah L Hanley, Tae Yeon Yoo, Matthew Sonnett, Daniel J Needleman, Timothy J Mitchison
The chromosomal passenger complex (CPC) is a conserved, essential regulator of cell division. As such, significant anti-cancer drug development efforts have been focused on targeting it, most notably by inhibiting its AURKB kinase subunit. The CPC is activated by AURKB-catalyzed autophosphorylation on multiple subunits, but how this regulates CPC interactions with other mitotic proteins remains unclear. We investigated the hydrodynamic behavior of the CPC in Xenopus laevis egg cytosol using sucrose gradient sedimentation and in HeLa cells using fluorescence correlation spectroscopy...
June 1, 2017: Molecular Biology of the Cell
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
#18
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/28369513/identification-and-characterization-of-aurora-kinase-b-and-c-variants-associated-with-maternal-aneuploidy
#19
Alexandra L Nguyen, Diego Marin, Anbo Zhou, Amanda S Gentilello, Evan M Smoak, Zubing Cao, Anastasia Fedick, Yujue Wang, Deanne Taylor, Richard T Scott, Jinchuan Xing, Nathan Treff, Karen Schindler
STUDY QUESTION: Are single nucleotide variants (SNVs) in Aurora kinases B and C (AURKB, AURKC) associated with risk of aneuploid conception? SUMMARY ANSWER: Two SNVs were found in patients with extreme aneuploid concepti rates with respect to their age; one variant, AURKC p.I79V, is benign, while another, AURKB p.L39P, is a potential gain-of-function mutant with increased efficiency in promoting chromosome alignment. WHAT IS KNOWN ALREADY: Maternal age does not always predict aneuploidy risk, and rare gene variants can be drivers of disease...
June 1, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28359584/specialize-and-divide-twice-functions-of-three-aurora-kinase-homologs-in-mammalian-oocyte-meiotic-maturation
#20
REVIEW
Alexandra L Nguyen, Karen Schindler
The aurora kinases (AURKs) comprise an evolutionarily conserved family of serine/threonine kinases involved in mitosis and meiosis. While most mitotic cells express two AURK isoforms (AURKA and AURKB), mammalian germ cells also express a third, AURKC. Although much is known about the functions of the kinases in mitosis, less is known about how the three isoforms function to coordinate meiosis. This review is aimed at describing what is known about the three isoforms in female meiosis, the similarities and differences between kinase functions, and speculates as to why mammalian germ cells require expression of three AURKs instead of two...
May 2017: Trends in Genetics: TIG
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