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https://www.readbyqxmd.com/read/28178520/identification-of-a-sgo2-dependent-but-mad2-independent-pathway-controlling-anaphase-onset-in-fission-yeast
#1
John C Meadows, Theresa C Lancaster, Graham J Buttrick, Alicja M Sochaj, Liam J Messin, Maria Del Mar Mora-Santos, Kevin G Hardwick, Jonathan B A Millar
The onset of anaphase is triggered by activation of the anaphase-promoting complex/cyclosome (APC/C) following silencing of the spindle assembly checkpoint (SAC). APC/C triggers ubiquitination of Securin and Cyclin B, which leads to loss of sister chromatid cohesion and inactivation of Cyclin B/Cdk1, respectively. This promotes relocalization of Aurora B kinase and other components of the chromosome passenger complex (CPC) from centromeres to the spindle midzone. In fission yeast, this is mediated by Clp1 phosphatase-dependent interaction of CPC with Klp9/MKLP2 (kinesin-6)...
February 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28177905/trap1-protein-signature-predicts-outcome-in-human-metastatic-colorectal-carcinoma
#2
Francesca Maddalena, Vittorio Simeon, Giulia Vita, Annamaria Bochicchio, Luciana Possidente, Lorenza Sisinni, Giacomo Lettini, Valentina Condelli, Danilo Swann Matassa, Valeria Li Bergolis, Alberto Fersini, Sante Romito, Michele Aieta, Antonio Ambrosi, Franca Esposito, Matteo Landriscina
TRAP1 is a HSP90 molecular chaperone upregulated in colorectal carcinomas and involved in control of intracellular signaling, cell cycle, apoptosis and drug resistance, stemness and bioenergetics through co-traslational regulation of a network of client proteins. Thus, the clinical significance of TRAP1 protein network was analyzed in human colorectal cancers. TRAP1 and/or its client proteins were quantified, by immunoblot analysis, in 60 surgical specimens of colorectal carcinomas at different stages and, by immunohistochemistry, in 9 colorectal adenomatous polyps, 11 in situ carcinomas and 55 metastatic colorectal tumors...
February 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28176922/inhibition-of-skp2-sensitizes-lung-cancer-cells-to-paclitaxel
#3
Tonghai Huang, Lin Yang, Guangsuo Wang, Guanggui Ding, Bin Peng, Yuxin Wen, Zheng Wang
S-phase kinase-associated protein 2 (Skp2) is an E3 ubiquitin ligase and plays an important role in the control of cell cycle progression. Skp2 is upregulated in several cancers, including lung cancers, but the role of Skp2 in the tumorigenesis and anticancer drug resistance in human lung cancer remains to be determined. We report here that Skp2 positively regulated mitotic arrest deficient 2 (MAD2) expression and that inhibition of Skp2 sensitizes human lung cancer cells to paclitaxel. Knockdown of Skp2 by small interfering RNA (siRNA) decreased Mad2 messenger RNA (mRNA) and protein levels in A549 and NCI-H1975 cells, accompanied with upregulation of p27 but decrease of the phosphorylation of retinoblastoma (Rb)...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28157697/trip13-impairs-mitotic-checkpoint-surveillance-and-is-associated-with-poor-prognosis-in-multiple-myeloma
#4
Yi Tao, Guang Yang, Hongxing Yang, Dongliang Song, Liangning Hu, Bingqian Xie, Houcai Wang, Lu Gao, Minjie Gao, Hongwei Xu, Zhijian Xu, Xiaosong Wu, Yiwen Zhang, Weiliang Zhu, Fenghuang Zhan, Jumei Shi
AAA-ATPase TRIP13 is one of the chromosome instability gene recently established in multiple myeloma (MM), the second most common and incurable hematological malignancy. However, the specific function of TRIP13 in MM is largely unknown. Using sequential gene expression profiling, we demonstrated that high TRIP13 expression levels were positively correlated with progression, disease relapse, and poor prognosis in MM patients. Overexpressing human TRIP13 in myeloma cells prompted cell growth and drug resistance, and overexpressing murine TRIP13, which shares 93% sequence identity with human TRIP13, led to colony formation of NIH/3T3 fibroblasts in vitro and tumor formation in vivo...
February 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28112196/the-kinetochore-dependent-and-independent-formation-of-the-cdc20-mad2-complex-and-its-functions-in-hela-cells
#5
Jianquan Li, Nanmao Dang, Daniel James Wood, Jun-Yong Huang
The mitotic checkpoint complex (MCC) is formed from two sub-complexes of CDC20-MAD2 and BUBR1-BUB3, and current models suggest that it is generated exclusively by the kinetochores after nuclear envelope breakdown (NEBD). However, neither sub-complex has been visualised in vivo, and when and where they are formed during the cell cycle and their response to different SAC conditions remains elusive. Using single cell analysis in HeLa cells, we show that the CDC20-MAD2 complex is cell cycle regulated with a "Bell" shaped profile and peaks at prometaphase...
January 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28105216/identification-of-potential-therapeutic-targets-for-colorectal-cancer-by-bioinformatics-analysis
#6
Ming Yan, Maomin Song, Rixing Bai, Shi Cheng, Wenmao Yan
The aim of the present study was to identify potential therapeutic targets for colorectal cancer (CRC). The gene expression profile GSE32323, containing 34 samples, including 17 specimens of CRC tissues and 17 of paired normal tissues from CRC patients, was downloaded from the Gene Expression Omnibus database. Following data preprocessing using the Affy and preprocessCore packages, the differentially-expressed genes (DEGs) between the two types of samples were identified with the Linear Models for Microarray Analysis package...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28102834/basis-of-catalytic-assembly-of-the-mitotic-checkpoint-complex
#7
Alex C Faesen, Maria Thanasoula, Stefano Maffini, Claudia Breit, Franziska Müller, Suzan van Gerwen, Tanja Bange, Andrea Musacchio
Accurate genome inheritance by daughter cells requires that sister chromatids in the mother attach to microtubules emanating from opposite poles of the mitotic spindle (bi-orientation). A surveillance mechanism named the spindle assembly checkpoint (SAC) monitors the microtubule attachment process, temporarily halting sister chromatid separation and mitotic exit until completion of bi-orientation1. SAC failure results in abnormal chromosome numbers (aneuploidy), a hallmark of many tumours. The HORMA domain protein MAD2 is a subunit of the SAC effector mitotic checkpoint complex (MCC)...
January 19, 2017: Nature
https://www.readbyqxmd.com/read/28096334/role-of-cct-chaperonin-in-the-disassembly-of-mitotic-checkpoint-complexes
#8
Sharon Kaisari, Danielle Sitry-Shevah, Shirly Miniowitz-Shemtov, Adar Teichner, Avram Hershko
The mitotic checkpoint system prevents premature separation of sister chromatids in mitosis and thus ensures the fidelity of chromosome segregation. When this checkpoint is active, a mitotic checkpoint complex (MCC), composed of the checkpoint proteins Mad2, BubR1, Bub3, and Cdc20, is assembled. MCC inhibits the ubiquitin ligase anaphase promoting complex/cyclosome (APC/C), whose action is necessary for anaphase initiation. When the checkpoint signal is turned off, MCC is disassembled, a process required for exit from checkpoint-arrested state...
January 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28072388/a-sequential-multi-target-mps1-phosphorylation-cascade-promotes-spindle-checkpoint-signaling
#9
Zhejian Ji, Haishan Gao, Luying Jia, Bing Li, Hongtao Yu
The master spindle checkpoint kinase Mps1 senses kinetochore-microtubule attachment and promotes checkpoint signaling to ensure accurate chromosome segregation. The kinetochore scaffold Knl1, when phosphorylated by Mps1, recruits checkpoint complexes Bub1-Bub3 and BubR1-Bub3 to unattached kinetochores. Active checkpoint signaling ultimately enhances the assembly of the mitotic checkpoint complex (MCC) consisting of BubR1-Bub3, Mad2, and Cdc20, which inhibits the anaphase-promoting complex or cyclosome bound to Cdc20 (APC/C(Cdc20)) to delay anaphase onset...
January 10, 2017: ELife
https://www.readbyqxmd.com/read/28017606/generation-of-a-spindle-checkpoint-arrest-from-synthetic-signaling-assemblies
#10
Ivan Yuan, Ioanna Leontiou, Priya Amin, Karen M May, Sadhbh Soper Ní Chafraidh, Eliška Zlámalová, Kevin G Hardwick
The spindle checkpoint acts as a mitotic surveillance system, monitoring interactions between kinetochores and spindle microtubules and ensuring high-fidelity chromosome segregation [1-3]. The checkpoint is activated by unattached kinetochores, and Mps1 kinase phosphorylates KNL1 on conserved MELT motifs to generate a binding site for the Bub3-Bub1 complex [4-7]. This leads to dynamic kinetochore recruitment of Mad proteins [8, 9], a conformational change in Mad2 [10-12], and formation of the mitotic checkpoint complex (MCC: Cdc20-Mad3-Mad2 [13-15])...
January 9, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/27835911/prognostic-and-predictive-values-of-cdk1-and-mad2l1-in-lung-adenocarcinoma
#11
Yuan-Xiang Shi, Tao Zhu, Ting Zou, Wei Zhuo, Yi-Xin Chen, Ma-Sha Huang, Wei Zheng, Chen-Jing Wang, Xi Li, Xiao-Yuan Mao, Wei Zhang, Hong-Hao Zhou, Ji-Ye Yin, Zhao-Qian Liu
Lung cancer remains as the leading cause of cancer-related death worldwide, and lung adenocarcinoma (LUAD) is the most common histological subtype. This study aims to investigate biomarkers associated with cancer progression and prognosis of LUAD. We integrated expression profiles of 668 lung cancer patients in five datasets from the Gene Expression Omnibus (GEO) and identified a panel of differentially expressed genes (DEGs). Function enrichment analysis highlighted that these genes were closely associated with the carcinogenesis of LUAD, such as cell cycle, ECM-receptor interaction and p53 signaling pathway...
November 9, 2016: Oncotarget
https://www.readbyqxmd.com/read/27713128/spc24-is-required-for-meiotic-kinetochore-microtubule-attachment-and-production-of-euploid-eggs
#12
Teng Zhang, Yang Zhou, Hong-Hui Wang, Tie-Gang Meng, Lei Guo, Xue-Shan Ma, Wei Shen, Heide Schatten, Qing-Yuan Sun
Mammalian oocytes are particularly error prone in chromosome segregation during two successive meiotic divisions. The proper kinetochore-microtubule attachment is a prerequisite for faithful chromosome segregation during meiosis. Here, we report that Spc24 localizes at the kinetochores during mouse oocyte meiosis. Depletion of Spc24 using specific siRNA injection caused defective kinetochore-microtubule attachments and chromosome misalignment, and accelerated the first meiosis by abrogating the kinetochore recruitment of spindle assembly checkpoint protein Mad2, leading to a high incidence of aneuploidy...
October 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27697601/overcoming-cisplatin-resistance-in-non-small-cell-lung-cancer-with-mad2-silencing-sirna-delivered-systemically-using-egfr-targeted-chitosan-nanoparticles
#13
Ana Vanessa Nascimento, Amit Singh, Hassan Bousbaa, Domingos Ferreira, Bruno Sarmento, Mansoor M Amiji
Efficiency of chemotherapy is often limited by low therapeutic index of the drug as well as emergence of inherent and acquired drug resistance in cancer cells. As a common strategy to overcome drug resistance, higher doses of chemo-agents are administered. However, adverse side effects are usually increased as a consequence. A potentially effective approach is to combine chemotherapy with other therapeutic strategies such as small interfering RNAs (siRNAs) that allow the use of lower yet efficient doses of the anticancer drugs...
January 1, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/27693251/inhibition-of-cdk7-bypasses-spindle-assembly-checkpoint-via-premature-cyclin-b-degradation-during-oocyte-meiosis
#14
HaiYang Wang, Yu-Jin Jo, Tian-Yi Sun, Suk Namgoong, Xiang-Shun Cui, Jeong Su Oh, Nam-Hyung Kim
To ensure accurate chromosome segregation, the spindle assembly checkpoint (SAC) delays anaphase onset by preventing the premature activation of anaphase-promoting complex/cyclosome (APC/C) until all kinetochores are attached to the spindle. Although an escape from mitosis in the presence of unsatisfied SAC has been shown in several cancer cells, it has not been reported in oocyte meiosis. Here, we show that CDK7 activity is required to prevent a bypass of SAC during meiosis I in mouse oocytes. Inhibition of CDK7 using THZ1 accelerated the first meiosis, leading to chromosome misalignment, lag of chromosomes during chromosome segregation, and a high incidence of aneuploidy...
December 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27664031/c-terminal-region-of-mad2-plays-an-important-role-during-mitotic-spindle-checkpoint-in-fission-yeast-schizosaccharomyces-pombe
#15
Gaurav Kumar Singh, Sharanbasappa Shrimant Karade, Rajeev Ranjan, Nafees Ahamad, Shakil Ahmed
The mitotic arrest deficiency 2 (Mad2) protein is an essential component of the spindle assembly checkpoint that interacts with Cdc20/Slp1 and inhibit its ability to activate anaphase promoting complex/cyclosome (APC/C). In bladder cancer cell line the C-terminal residue of the mad2 gene has been found to be deleted. In this study we tried to understand the role of the C-terminal region of mad2 on the spindle checkpoint function. To envisage the role of C-terminal region of Mad2, we truncated 25 residues of Mad2 C-terminal region in fission yeast S...
February 2017: Molecular Biology Reports
https://www.readbyqxmd.com/read/27618268/bub3-bub1-binding-to-spc7-knl1-toggles-the-spindle-checkpoint-switch-by-licensing-the-interaction-of-bub1-with-mad1-mad2
#16
Maria Del Mar Mora-Santos, America Hervas-Aguilar, Katharina Sewart, Theresa C Lancaster, John C Meadows, Jonathan B A Millar
The spindle assembly checkpoint (SAC) ensures that sister chromatids do not separate until all chromosomes are attached to spindle microtubules and bi-oriented. Spindle checkpoint proteins, including Mad1, Mad2, Mad3 (BubR1), Bub1, Bub3, and Mph1 (Mps1), are recruited to unattached and/or tensionless kinetochores. SAC activation catalyzes the conversion of soluble Mad2 (O-Mad2) into a form (C-Mad2) that binds Cdc20, BubR1, and Bub3 to form the mitotic checkpoint complex (MCC), a potent inhibitor of the anaphase-promoting complex (APC/C)...
October 10, 2016: Current Biology: CB
https://www.readbyqxmd.com/read/27601671/p31comet-a-member-of-the-synaptonemal-complex-participates-in-meiotic-dsb-formation-in-rice
#17
Jianhui Ji, Ding Tang, Yi Shen, Zhihui Xue, Hongjun Wang, Wenqing Shi, Chao Zhang, Guijie Du, Yafei Li, Zhukuan Cheng
The human mitotic arrest-deficient 2 (Mad2) binding protein p31(comet) participates in the spindle checkpoint and coordinates cell cycle events in mitosis although its function in meiosis remains unknown in all organisms. Here, we reveal P31(comet) as a synaptonemal complex (SC) protein in rice (Oryza sativa L.). In p31(comet), homologous pairing and synapsis are eliminated, leading to the homologous nondisjunction and complete sterility. The failure in loading of histone H2AX phosphorylation (γH2AX) in p31(comet), together with the suppressed chromosome fragmentation in rice completion of meiotic recombination 1 (com1) p31(comet) and radiation sensitive 51c (rad51c) p31(comet) double mutants, indicates that P31(comet) plays an essential role in double-strand break (DSB) formation...
September 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27496292/absence-of-a-conventional-spindle-mitotic-checkpoint-in-the-binucleated-single-celled-parasite-giardia-intestinalis
#18
Kristyna Markova, Magdalena Uzlikova, Pavla Tumova, Klara Jirakova, Guy Hagen, Jaroslav Kulda, Eva Nohynkova
The spindle assembly checkpoint (SAC) joins the machinery of chromosome-to-spindle microtubule attachment with that of the cell cycle to prevent missegregation of chromosomes during mitosis. Although a functioning SAC has been verified in a limited number of organisms, it is regarded as an evolutionarily conserved safeguard mechanism. In this report, we focus on the existence of the SAC in a single-celled parasitic eukaryote, Giardia intestinalis. Giardia belongs to Excavata, a large and diverse supergroup of unicellular eukaryotes in which SAC control has been nearly unexplored...
October 2016: European Journal of Cell Biology
https://www.readbyqxmd.com/read/27405720/traip-is-involved-in-chromosome-alignment-and-sac-regulation-in-mouse-oocyte-meiosis
#19
Yi-Feng Yuan, Yi-Xin Ren, Peng Yuan, Li-Ying Yan, Jie Qiao
Recent whole-exome sequencing (WES) studies demonstrated that TRAIP is associated with primordial dwarfism. Although TRAIP was partially studied in mitosis, its function in oocyte meiosis remained unknown. In this study, we investigated the roles of TRAIP during mouse oocyte meiosis. TRAIP was stably expressed during oocytes meiosis and co-localized with CREST at the centromere region. Knockdown of TRAIP led to DNA damage, as revealed by the appearance of γH2AX. Although oocytes meiotic maturation was not affected, the proportions of misaligned chromosomes and aneuploidy were elevated after TRAIP knockdown, suggesting TRAIP is required for stable kinetochore-microtubule (K-MT) attachment...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27374329/mitotic-checkpoint-regulators-control-insulin-signaling-and-metabolic-homeostasis
#20
Eunhee Choi, Xiangli Zhang, Chao Xing, Hongtao Yu
Insulin signaling regulates many facets of animal physiology. Its dysregulation causes diabetes and other metabolic disorders. The spindle checkpoint proteins MAD2 and BUBR1 prevent precocious chromosome segregation and suppress aneuploidy. The MAD2 inhibitory protein p31(comet) promotes checkpoint inactivation and timely chromosome segregation. Here, we show that whole-body p31(comet) knockout mice die soon after birth and have reduced hepatic glycogen. Liver-specific ablation of p31(comet) causes insulin resistance, hyperinsulinemia, glucose intolerance, and hyperglycemia and diminishes the plasma membrane localization of the insulin receptor (IR) in hepatocytes...
July 28, 2016: Cell
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