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https://www.readbyqxmd.com/read/29775579/a-mad2-mediated-translational-regulatory-mechanism-promoting-s-phase-cyclin-synthesis-controls-origin-firing-and-survival-to-replication-stress
#1
Sophie Gay, Daniele Piccini, Christopher Bruhn, Sara Ricciardi, Paolo Soffientini, Walter Carotenuto, Stefano Biffo, Marco Foiani
Cell survival to replication stress depends on the activation of the Mec1ATR -Rad53 checkpoint response that protects the integrity of stalled forks and controls the origin firing program. Here we found that Mad2, a member of the spindle assembly checkpoint (SAC), contributes to efficient origin firing and to cell survival in response to replication stress. We show that Rad53 and Mad2 promote S-phase cyclin expression through different mechanisms: while Rad53 influences Clb5,6 degradation, Mad2 promotes their protein synthesis...
May 17, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29620143/exploring-the-molecular-mechanisms-of-osteosarcoma-by-the-integrated-analysis-of-mrnas-and-mirna-microarrays
#2
Hao Shen, Wei Wang, Bingbing Ni, Qiang Zou, Hua Lu, Zhanchao Wang
Osteosarcoma (OS) is the most frequently occurring primary bone malignancy with a rapid progression and poor survival. In the present study, in order to examine the molecular mechanisms of OS, we analyzed the microarray of GSE28425. GSE28425 was downloaded from Gene Expression Omnibus, which also included the miRNA expression profile, GSE28423, and the mRNA expression profile, GSE28424. Each of the expression profiles included 19 OS cell lines and 4 normal bones. The differentially expressed genes (DEGs) and differentially expressed miRNAs (DE-miRNAs) were screened using the limma package in Bioconductor...
March 27, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29555820/aurora-a-kinase-activity-is-required-to-maintain-the-spindle-assembly-checkpoint-active-during-pro-metaphase
#3
Thibault Courtheoux, Alghassimou Diallo, Arun Prasath Damodaran, David Reboutier, Erwan Watrin, Claude Prigent
During the prometaphase stage of mitosis, the cell builds a bipolar spindle of microtubules that mechanically segregates sister chromatids for two daughter cells in anaphase. The spindle assembly checkpoint (SAC) is a quality control mechanism that monitors proper attachment of microtubules to chromosome kinetochores during prometaphase. Segregation occurs only when each chromosome is bi-oriented with each kinetochore pair attached to microtubules emanating from opposite spindle poles. Overexpression of the protein kinase Aurora A is a feature of various cancers and is thought to enable tumour cells to bypass the SAC leading to aneuploidy...
March 19, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29533809/roles-of-msh2-and-msh6-in-cadmium-induced-g2-m-checkpoint-arrest-in-arabidopsis-roots
#4
Xia Cao, Hetong Wang, Defeng Zhuang, He Zhu, Yanli Du, Zhibo Cheng, Weina Cui, Hilary J Rogers, Qianru Zhang, Chunjun Jia, Yuesuo Yang, Peidong Tai, Futi Xie, Wan Liu
DNA mismatch repair (MMR) proteins have been implicated in sensing and correcting DNA damage, and in governing cell cycle progression in the presence of structurally anomalous nucleotide lesions induced by different stresses in mammalian cells. Here, Arabidopsis seedlings were grown hydroponically on 0.5 × MS media containing cadmium (Cd) at 0-4.0 mg L-1 for 5 d. Flow cytometry results indicated that Cd stress induced a G2/M cell cycle arrest both in MLH1-, MSH2-, MSH6-deficient, and in WT roots, associated with marked changes of G2/M regulatory genes, including ATM, ATR, SOG1, BRCA1, WEE1, CYCD4; 1, MAD2, CDKA;1, CYCB1; 2 and CYCB1; 1...
June 2018: Chemosphere
https://www.readbyqxmd.com/read/29465507/brca1-and-mad2-are-coexpressed-and-are-prognostic-indicators-in-tubo-ovarian-high-grade-serous-carcinoma
#5
Tara Byrne, Laura Nelson, James P Beirne, Daniel Sharpe, Jennifer E Quinn, W Glenn McCluggage, Tracy Robson, Fiona Furlong
OBJECTIVES: The aim of this study was to investigate the relationship between BRCA1 and mitotic arrest deficiency protein 2 (MAD2) protein expression, as determined by immunohistochemistry, and clinical outcomes in epithelial ovarian carcinoma (EOC). METHODS: A tissue microarray consisting of 94 formalin-fixed paraffin-embedded EOC with fully matched clinicopathological data were immunohistochemically stained with anti-BRCA1 and anti-MAD2 antibodies. The cores were scored in a semiquantitative manner evaluating nuclear staining intensity and extent...
March 2018: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/29432156/role-of-ubiquitylation-of-components-of-mitotic-checkpoint-complex-in-their-dissociation-from-anaphase-promoting-complex-cyclosome
#6
Danielle Sitry-Shevah, Sharon Kaisari, Adar Teichner, Shirly Miniowitz-Shemtov, Avram Hershko
The mitotic checkpoint system ensures the fidelity of chromosome segregation in mitosis by preventing premature initiation of anaphase until correct bipolar attachment of chromosomes to the mitotic spindle is reached. It promotes the assembly of a mitotic checkpoint complex (MCC), composed of BubR1, Bub3, Cdc20, and Mad2, which inhibits the activity of the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase. When the checkpoint is satisfied, anaphase is initiated by the disassembly of MCC. Previous studies indicated that the dissociation of APC/C-bound MCC requires ubiquitylation and suggested that the target of ubiquitylation is the Cdc20 component of MCC...
February 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29425500/trip13-functions-in-the-establishment-of-the-spindle-assembly-checkpoint-by-replenishing-o-mad2
#7
Hoi Tang Ma, Randy Y C Poon
The spindle assembly checkpoint (SAC) prevents premature segregation of chromosomes during mitosis. This process requires structural remodeling of MAD2 from O-MAD2 to C-MAD2 conformation. After the checkpoint is satisfied, C-MAD2 is reverted to O-MAD2 to allow anaphase-promoting complex/cyclosome (APC/C) to trigger anaphase. Recently, the AAA+ -ATPase TRIP13 was shown to act in concert with p31comet to catalyze C- to O-MAD2. Paradoxically, although C-MAD2 is present in TRIP13-deficient cells, the SAC cannot be activated...
February 6, 2018: Cell Reports
https://www.readbyqxmd.com/read/29425499/bub1-is-essential-for-the-viability-of-human-cells-in-which-the-spindle-assembly-checkpoint-is-compromised
#8
Jonne A Raaijmakers, Roy G H P van Heesbeen, Vincent A Blomen, Louise M E Janssen, Ferdy van Diemen, Thijn R Brummelkamp, René H Medema
The spindle assembly checkpoint (SAC) ensures faithful segregation of chromosomes. Although most mammalian cell types depend on the SAC for viability, we found that human HAP1 cells can grow SAC independently. We generated MAD1- and MAD2-deficient cells and mutagenized them to identify synthetic lethal interactions, revealing that chromosome congression factors become essential upon SAC deficiency. Besides expected hits, we also found that BUB1 becomes essential in SAC-deficient cells. We found that the BUB1 C terminus regulates alignment as well as recruitment of CENPF...
February 6, 2018: Cell Reports
https://www.readbyqxmd.com/read/29408509/mad2-p31-comet-axis-deficiency-reduces-cell-proliferation-migration-and-sensitivity-of-microtubule-interfering-agents-in-glioma
#9
Dang Wu, Lepeng Wang, Yanhong Yang, Jin Huang, Yuhua Hu, Yongwei Shu, Jingyu Zhang, Jing Zheng
Mitotic arrest deficient-like-1 (MAD2, also known as MAD2L1) is thought to be an important spindle assembly checkpoint protein, which ensures accurate chromosome segregation and is closely associated with poor prognosis in many cancer. As a MAD2 binding protein, p31comet counteracts the function of MAD2 and leads to mitotic checkpoint silence. In this study, we explore the function of MAD2-p31comet axis in malignant glioma cells. Our results showed that disruption of MAD2-p31comet axis by MAD2 knockdown or p31comet overexpression suppressed cell proliferation, survival and migration of glioma, indicating that MAD2-p31comet axis is required for maintaining glioma cells malignancy...
March 25, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29362225/the-escrt-protein-chmp4c-regulates-mitotic-spindle-checkpoint-signaling
#10
Eleni Petsalaki, Maria Dandoulaki, George Zachos
The mitotic spindle checkpoint delays anaphase onset in the presence of unattached kinetochores, and efficient checkpoint signaling requires kinetochore localization of the Rod-ZW10-Zwilch (RZZ) complex. In the present study, we show that human Chmp4c, a protein involved in membrane remodeling, localizes to kinetochores in prometaphase but is reduced in chromosomes aligned at the metaphase plate. Chmp4c promotes stable kinetochore-microtubule attachments and is required for proper mitotic progression, faithful chromosome alignment, and segregation...
March 5, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29220700/prognostic-importance-of-aurora-kinases-and-mitotic-spindle-genes-transcript-levels-in-myelodysplastic-syndrome
#11
Daniela de Paula Borges, Antônio Wesley Araújo Dos Santos, Carlos Roberto Koscky Paier, Howard Lopes Ribeiro, Marília Braga Costa, Izabelle Rocha Farias, Roberta Taiane Germano de Oliveira, Ivo Gabriel da Frota França, Gabrielle Melo Cavalcante, Sílvia Maria Meira Magalhães, Ronald Feitosa Pinheiro
Myelodysplastic syndrome (MDS) are a heterogeneous group of clonal disease characterized by insufficiency of bone marrow, increase of apoptosis and increased risk of acute leukemia progression. Proteins related to the mitotic spindle (AURKA, AURKB, TPX2), to the mitotic checkpoint (MAD2, CDC20) and the regulation of the cell cycle (p21) are directly related to chromosomal stability and tumor development. This study aimed to evaluate the mRNA expression levels of these genes in 101 MDS patients using a real-time PCR methodology...
January 2018: Leukemia Research
https://www.readbyqxmd.com/read/29208896/mechanistic-insight-into-trip13-catalyzed-mad2-structural-transition-and-spindle-checkpoint-silencing
#12
Melissa L Brulotte, Byung-Cheon Jeong, Faxiang Li, Bing Li, Eric B Yu, Qiong Wu, Chad A Brautigam, Hongtao Yu, Xuelian Luo
The spindle checkpoint maintains genomic stability and prevents aneuploidy. Unattached kinetochores convert the latent open conformer of the checkpoint protein Mad2 (O-Mad2) to the active closed conformer (C-Mad2), bound to Cdc20. C-Mad2-Cdc20 is incorporated into the mitotic checkpoint complex (MCC), which inhibits the anaphase-promoting complex/cyclosome (APC/C). The C-Mad2-binding protein p31comet and the ATPase TRIP13 promote MCC disassembly and checkpoint silencing. Here, using nuclear magnetic resonance (NMR) spectroscopy, we show that TRIP13 and p31comet catalyze the conversion of C-Mad2 to O-Mad2, without disrupting its stably folded core...
December 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/29186573/conformational-dynamics-of-the-hop1-horma-domain-reveal-a-common-mechanism-with-the-spindle-checkpoint-protein-mad2
#13
Alan M V West, Elizabeth A Komives, Kevin D Corbett
The HORMA domain is a highly conserved protein-protein interaction module found in eukaryotic signaling proteins including the spindle assembly checkpoint protein Mad2 and the meiotic HORMAD proteins. HORMA domain proteins interact with short 'closure motifs' in partner proteins by wrapping their C-terminal 'safety belt' region entirely around these motifs, forming topologically-closed complexes. Closure motif binding and release requires large-scale conformational changes in the HORMA domain, but such changes have only been observed in Mad2...
January 9, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29162720/direct-interactions-of-mitotic-arrest-deficient-1-mad1-domains-with-each-other-and-mad2-conformers-are-required-for-mitotic-checkpoint-signaling
#14
Wenbin Ji, Yibo Luo, Ejaz Ahmad, Song-Tao Liu
As a sensitive signaling system, the mitotic checkpoint ensures faithful chromosome segregation by delaying anaphase onset even when a single kinetochore is unattached to mitotic spindle microtubules. The key signal amplification reaction for the checkpoint is the conformational conversion of "open" mitotic arrest deficient 2 (O-MAD2) into "closed" MAD2 (C-MAD2). The reaction has been suggested to be catalyzed by an unusual catalyst, a MAD1:C-MAD2 tetramer, but how the catalysis is executed and regulated remains elusive...
January 12, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29158164/lmo7-exerts-an-effect-on-mitosis-progression-and-the-spindle-assembly-checkpoint
#15
Yao-Wei Tzeng, Dai-Yu Li, Yvan Chen, Cheng-Hsiu Yang, Chih-Yun Chang, Yue-Li Juang
LMO7 (LIM domain only 7) is a transcription regulator for expression of many Emery-Dreifuss muscular dystrophy-relevant genes, and binds to α-actinin and AF6/afadin at adherens junctions for epithelial cell-cell adhesion. In this study, we found that human LMO7 interacted with the spindle assembly checkpoint (SAC) protein MAD1. LMO7 colocalized with actin filaments at the cell membrane but did not colocalize with MAD1 at kinetochores in prometaphase. Our observations reveal that overexpression but not depletion of LMO7 caused a SAC defect, and that the LIM domain of LMO7 was a determinant of its ability to interfere with kinetochore localization of the SAC proteins MAD2 and BUBR1 and cause a SAC defect though the LIM peptide itself did neither bind to MAD1, MAD2 and BUBR1 nor localize to the actin filaments...
January 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29028969/correlation-of-defective-mitotic-checkpoint-with-aberrantly-reduced-expression-of-mad2-protein-in-nasopharyngeal-carcinoma-cells
#16
Xianghong Wang, Dong-Yan Jin, Y C Wong, Annie L M Cheung, Abel C S Chun, Angela K F Lo, Yu Liu, Sai Wah Tsao
No abstract text is available yet for this article.
September 26, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28915607/coal-tar-pitch-extract-could-induce-chromosomal-instability-of-human-bronchial-epithelial-cells-mediated-by-spindle-checkpoint-related-proteins
#17
Peng Zhang, Zhitao Li, Na Wang, Guangcai Duan, Wei Wang, Yanming Feng, Yong Zhao, Lixia Wang, Hansong Zhu, Qiao Zhang, Xiaozhuan Liu, Weidong Wu, Yongjun Wu, Wu Yao, Jing Wang, Yiming Wu, Feifei Feng
Coal tar pitch (CTP) is a byproduct of coal tar distillation. The workers working with coal tar or in aluminum smelters, potrooms and carbon plants have the opportunities of exposing to coal tar pitch volatiles. Coal tar pitches from which polycyclic aromatic hydrocarbons (PAHs) originate have been shown to exhibit lung carcinogenicity in humans. Chromosomal instability (CIN) is a mechanism in carcinogenesis, however, whether CIN is involved in coal tar pitch-induced lung cancer remains elusive. In this present study, human bronchial epithelial cells (BEAS-2B) were first exposed to coal tar pitch extracts (CTPE) to induce a malignant transformation model...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28815566/maturation-promoting-factor-destabilization-mediates-human-chorionic-gonadotropin-induced-meiotic-resumption-in-rat-oocytes
#18
Meenakshi Tiwari, Shail K Chaube
Human chorionic gonadotropin (hCG) mimics the action of luteinizing hormone (LH) and triggers meiotic maturation and ovulation in mammals. The mechanism by which hCG triggers meiotic resumption in mammalian oocytes remains poorly understood. We aimed to find out the impact of hCG surge on morphological changes, adenosine 3',5'-cyclic monophosphate (cAMP), guanosine 3',5'-cyclic monophosphate (cGMP), cell division cycle 25B (Cdc25B), Wee1, early mitotic inhibitor 2 (Emi2), anaphase-promoting complex/cyclosome (APC/C), meiotic arrest deficient protein 2 (MAD2), phosphorylation status of cyclin-dependent kinase 1 (Cdk1), its activity and cyclin B1 expression levels during meiotic resumption from diplotene as well as metaphase-II (M-II) arrest in cumulus oocyte complexes (COCs)...
September 2017: Development, Growth & Differentiation
https://www.readbyqxmd.com/read/28695965/role-of-mad2-expression-during-the-early-development-of-the-sea-urchin
#19
Odile Bronchain, Wael Jdey, Laetitia Caraty, Brigitte Ciapa
Mitotic arrest deficient 2 (Mad2) belongs to the spindle assembly checkpoint (SAC), a mechanism that blocks progression of the cell cycle until microtubule attachment to kinetochores is complete. It has been found to be involved in the resistance of cancer cells to "anti-mitotic" drugs such as paclitaxel. Mad2 controls meiotic progression, but its role during sea urchin development had never been investigated. Furthermore, the existence of a SAC in this species had never been proved. The present data show that a Mad2 protein, highly homologous to that of humans, is expressed in this species...
2017: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/28678347/trap1-controls-cell-cycle-g2-m-transition-through-the-regulation-of-cdk1-and-mad2-expression-ubiquitination
#20
Lorenza Sisinni, Francesca Maddalena, Valentina Condelli, Giuseppe Pannone, Vittorio Simeon, Valeria Li Bergolis, Elvira Lopes, Annamaria Piscazzi, Danilo Swann Matassa, Carmela Mazzoccoli, Filomena Nozza, Giacomo Lettini, Maria Rosaria Amoroso, Pantaleo Bufo, Franca Esposito, Matteo Landriscina
Regulation of tumour cell proliferation by molecular chaperones is still a complex issue. Here, the role of the HSP90 molecular chaperone TRAP1 in cell cycle regulation was investigated in a wide range of human breast, colorectal, and lung carcinoma cell lines, and tumour specimens. TRAP1 modulates the expression and/or the ubiquitination of key cell cycle regulators through a dual mechanism: (i) transcriptional regulation of CDK1, CYCLIN B1, and MAD2, as suggested by gene expression profiling of TRAP1-silenced breast carcinoma cells; and (ii) post-transcriptional quality control of CDK1 and MAD2, being the ubiquitination of these two proteins enhanced upon TRAP1 down-regulation...
September 2017: Journal of Pathology
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