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Anaphase-promoting complex

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https://www.readbyqxmd.com/read/28637452/downregulation-of-talin-1-expression-associates-with-increased-proliferation-and-migration-of-vascular-smooth-muscle-cells-in-aortic-dissection
#1
Xiaolong Wei, Yudong Sun, Yani Wu, Jiang Zhu, Bin Gao, Han Yan, Zhiqing Zhao, Jian Zhou, Zaiping Jing
BACKGROUND: This study aimed to assessed whether Talin-1 is involved in the pathogenesis of aortic dissection via regulating vascular smooth muscle cell (VSMC) biological function. METHODS: Human aortic samples were obtained from organ donors who died from nonvascular diseases as normal controls and from patients undergoing surgical repair of thoracic aortic dissection. The expression level and distribution of Talin-1 were detected using westernblot analysis and immunohistochemistry in each sample...
June 20, 2017: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/28634351/a-dynamical-model-for-activating-and-silencing-the-mitotic-checkpoint
#2
Richard Henze, Peter Dittrich, Bashar Ibrahim
The spindle assembly checkpoint (SAC) is an evolutionarily conserved mechanism, exclusively sensitive to the states of kinetochores attached to microtubules. During metaphase, the anaphase-promoting complex/cyclosome (APC/C) is inhibited by the SAC but it rapidly switches to its active form following proper attachment of the final spindle. It had been thought that APC/C activity is an all-or-nothing response, but recent findings have demonstrated that it switches steadily. In this study, we develop a detailed mathematical model that considers all 92 human kinetochores and all major proteins involved in SAC activation and silencing...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28617439/cdc20-directs-proteasome-mediated-degradation-of-the-tumor-suppressor-smar1-in-higher-grades-of-cancer-through-the-anaphase-promoting-complex
#3
Debasish Paul, Suvankar Ghorai, U S Dinesh, Praveenkumar Shetty, Samit Chattopadhyay, Manas Kumar Santra
The Tumor suppressor SMAR1 (scaffold matrix attachment region binding protein 1) has a crucial role in maintaining genomic stability, cell cycle progression and apoptosis.Our previous finding showed that it is highly suppressed in higher grade of cancer. However, the underlying mechanism of this suppression was not well understood. In this study, we show that SMAR1 expression levels are controlled at the proteasomal level by five RING finger E3 ubiquitin ligases including, Cdc20, a substrate receptor of ubiquitin ligase APC/C complex...
June 15, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28607478/precocious-centriole-disengagement-and-centrosome-fragmentation-induced-by-mitotic-delay
#4
Menuka Karki, Neda Keyhaninejad, Charles B Shuster
The spindle assembly checkpoint (SAC) delays mitotic progression until all sister chromatid pairs achieve bi-orientation, and while the SAC can maintain mitotic arrest for extended periods, moderate delays in mitotic progression have significant effects on the resulting daughter cells. Here we show that when retinal-pigmented epithelial (RPE1) cells experience mitotic delay, there is a time-dependent increase in centrosome fragmentation and centriole disengagement. While most cells with disengaged centrioles maintain spindle bipolarity, clustering of disengaged centrioles requires the kinesin-14, HSET...
June 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28604711/the-anaphase-promoting-complex-impacts-repair-choice-by-protecting-ubiquitin-signalling-at-dna-damage-sites
#5
Kyungsoo Ha, Chengxian Ma, Han Lin, Lichun Tang, Zhusheng Lian, Fang Zhao, Ju-Mei Li, Bei Zhen, Huadong Pei, Suxia Han, Marcos Malumbres, Jianping Jin, Huan Chen, Yongxiang Zhao, Qing Zhu, Pumin Zhang
Double-strand breaks (DSBs) are repaired through two major pathways, homology-directed recombination (HDR) and non-homologous end joining (NHEJ). While HDR can only occur in S/G2, NHEJ can happen in all cell cycle phases (except mitosis). How then is the repair choice made in S/G2 cells? Here we provide evidence demonstrating that APC(Cdh1) plays a critical role in choosing the repair pathways in S/G2 cells. Our results suggest that the default for all DSBs is to recruit 53BP1 and RIF1. BRCA1 is blocked from being recruited to broken ends because its recruitment signal, K63-linked poly-ubiquitin chains on histones, is actively destroyed by the deubiquitinating enzyme USP1...
June 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28535376/dephosphorylation-of-the-ndc80-tail-stabilizes-kinetochore-microtubule-attachments-via-the-ska-complex
#6
Dhanya K Cheerambathur, Bram Prevo, Neil Hattersley, Lindsay Lewellyn, Kevin D Corbett, Karen Oegema, Arshad Desai
During cell division, genome inheritance is orchestrated by microtubule attachments formed at kinetochores of mitotic chromosomes. The primary microtubule coupler at the kinetochore, the Ndc80 complex, is regulated by Aurora kinase phosphorylation of its N-terminal tail. Dephosphorylation is proposed to stabilize kinetochore-microtubule attachments by strengthening electrostatic interactions of the tail with the microtubule lattice. Here, we show that removal of the Ndc80 tail, which compromises in vitro microtubule binding, has no effect on kinetochore-microtubule attachments in the Caenorhabditis elegans embryo...
May 22, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28516917/maternal-age-dependent-apc-c-mediated-decrease-in-securin-causes-premature-sister-chromatid-separation-in-meiosis-ii
#7
Ibtissem Nabti, Rosanna Grimes, Hema Sarna, Petros Marangos, John Carroll
Sister chromatid attachment during meiosis II (MII) is maintained by securin-mediated inhibition of separase. In maternal ageing, oocytes show increased inter-sister kinetochore distance and premature sister chromatid separation (PSCS), suggesting aberrant separase activity. Here, we find that MII oocytes from aged mice have less securin than oocytes from young mice and that this reduction is mediated by increased destruction by the anaphase promoting complex/cyclosome (APC/C) during meiosis I (MI) exit. Inhibition of the spindle assembly checkpoint (SAC) kinase, Mps1, during MI exit in young oocytes replicates this phenotype...
May 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28505105/new-functions-of-apc-c-ubiquitin-ligase-in-the-nervous-system-and-its-role-in-alzheimer-s-disease
#8
REVIEW
Tanja Fuchsberger, Ana Lloret, Jose Viña
The E3 ubiquitin ligase Anaphase Promoting Complex/Cyclosome (APC/C) regulates important processes in cells, such as the cell cycle, by targeting a set of substrates for degradation. In the last decade, APC/C has been related to several major functions in the nervous system, including axon guidance, synaptic plasticity, neurogenesis, and neuronal survival. Interestingly, some of the identified APC/C substrates have been related to neurodegenerative diseases. There is an accumulation of some degradation targets of APC/C in Alzheimer's disease (AD) brains, which suggests a dysregulation of the protein complex in the disorder...
May 14, 2017: International Journal of Molecular Sciences
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
#9
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/28479321/ska3-phosphorylated-by-cdk1-binds-ndc80-and-recruits-ska-to-kinetochores-to-promote-mitotic-progression
#10
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/28455985/coal-tar-pitch-extract-could-induce-chromosomal-instability-of-human-bronchial-epithelial-cells-mediated-by-spindle-checkpoint-related-proteins
#11
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...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28455357/fission-yeast-neddylation-ligase-dcn1-facilitates-cohesin-cleavage-and-chromosome-segregation-at-anaphase
#12
Lan Lin, Li Chen, Phong T Tran
Post-translational protein modification such as phosphorylation and ubiquitination are critical during mitosis to ensure proper timing and progression of chromosome segregation. It has been recently recognized that another type of protein modification - neddylation - may also regulate mitosis and chromosome segregation. The conserved protein DCN1 (defective cullin neddylation 1) has been shown, when knocked-down by RNAi, to result in multinucleated cells and/or blockage of cell proliferation. However, how DCN1 functions in mitosis and chromosome segregation is not known...
June 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28442047/increased-frequency-of-chromosome-congression-defects-and-aneuploidy-in-mouse-oocytes-cultured-at-lower-temperature
#13
Jitka Danadova, Natalie Matijescukova, Anna Mac Gillavry Danylevska, Martin Anger
Optimal culture conditions are essential for successful IVM of mammalian oocytes and for their further development into an embryo. In the present study we used live cell imaging microscopy to assess the effects of suboptimal culture temperature on various aspects of IVM, including duration of meiosis I, dynamics of polar body extrusion, chromosome congression, anaphase-promoting complex/cyclosome (APC/C) activation and aneuploidy. The data showed that even a small deviation from the optimal incubation temperature causes marked changes in the duration and synchronicity of meiosis, APC/C activity and the frequency of chromosome congression and segregation errors...
April 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28401073/structural-insight-into-anaphase-promoting-complex-3-structure-and-docking-with-a-natural-inhibitory-compound
#14
Hamzeh Rahimi, Mohammad Ali Shokrgozar, Armin Madadkar-Sobhani, Reza Mahdian, Alireza Foroumadi, Morteza Karimipoor
BACKGROUND: Anaphase promoting complex (APC) is the biggest Cullin-RING E3 ligase and is very important in cell cycle control; many anti-cancer agents target this. APC controls the onset of chromosome separation and mitotic exit through securin and cyclin B degradation, respectively. Its APC3 subunit identifies the APC activators-Cdh1 and Cdc20. MATERIALS AND METHODS: The structural model of the APC3 subunit of APC was developed by means of computational techniques; the binding of a natural inhibitory compound to APC3 was also investigated...
2017: Advanced Biomedical Research
https://www.readbyqxmd.com/read/28396402/apc-c-cdh1-rock2-pathway-controls-dendritic-integrity-and-memory
#15
Verónica Bobo-Jiménez, María Delgado-Esteban, Julie Angibaud, Irene Sánchez-Morán, Antonio de la Fuente, Javier Yajeya, U Valentin Nägerl, José Castillo, Juan P Bolaños, Angeles Almeida
Disruption of neuronal morphology contributes to the pathology of neurodegenerative disorders such as Alzheimer's disease (AD). However, the underlying molecular mechanisms are unknown. Here, we show that postnatal deletion of Cdh1, a cofactor of the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase in neurons [Cdh1 conditional knockout (cKO)], disrupts dendrite arborization and causes dendritic spine and synapse loss in the cortex and hippocampus, concomitant with memory impairment and neurodegeneration, in adult mice...
April 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28376205/association-of-uba6-specific-e2-use1-with-lung-tumorigenesis
#16
Seong-Jin Kim, Tae Hyeong Lee, Sang Hee Nam, Ji-Hong Kim, Sangho Oh, Yeon Sook Cho, Myeong Sup Lee, Sehoon Choi, Peter C W Lee
Background: The UBA6-specific E2 conjugating enzyme 1 (USE1) ubiquitin enzyme cascade is a poorly characterized arm of the ubiquitin-proteasome system. We investigated whether the UBA6-USE1 enzyme cascade plays a role in lung cancer tumorigenesis. Methods: USE1 expression was assessed in tumor-normal paired samples from 106 lung cancer patients by immunoblot. USE1 was stably overexpressed and knocked down in lung cancer cell lines to evaluate cell proliferation, colony formation, and invasion...
March 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28373167/anaphase-promoting-complex-adaptor-fzr1-cdh1-blocks-braf-signaling-both-by-targeting-braf-for-proteolytic-degradation-and-by-disrupting-braf-dimerization
#17
Chao Zhang, Gideon Bollag
Blocking dimerization and stimulating protein degradation are two mechanisms known to inhibit BRAF activity. The study reported by Wan and colleagues identifies BRAF as a substrate of the APC/C(FZR1)-ubiqutin-proteasome system. The interaction between FZR1 and BRAF also induces a conformational change that disrupts BRAF dimerization. These findings identify a dynamic interplay between FZR1 and BRAF with strong implications for cell-fate determination and the tumor suppressor role of FZR1. Cancer Discov; 7(4); 356-8...
April 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28366744/fission-yeast-apc15-stabilizes-mcc-cdc20-apc-c-complexes-ensuring-efficient-cdc20-ubiquitination-and-checkpoint-arrest
#18
Karen M May, Flora Paldi, Kevin G Hardwick
During mitosis, cells must segregate the replicated copies of their genome to their daughter cells with extremely high fidelity. Segregation errors lead to an abnormal chromosome number (aneuploidy), which typically results in disease or cell death [1]. Chromosome segregation and anaphase onset are initiated through the action of the multi-subunit E3 ubiquitin ligase known as the anaphase-promoting complex or cyclosome (APC/C [2]). The APC/C is inhibited by the spindle checkpoint in the presence of kinetochore attachment defects [3, 4]...
April 24, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28366743/different-functionality-of-cdc20-binding-sites-within-the-mitotic-checkpoint-complex
#19
Katharina Sewart, Silke Hauf
The mitotic checkpoint is a cellular safeguard that prevents chromosome missegregation in eukaryotic cells [1, 2]. Suboptimal functioning may foster chromosome missegregation in cancer cells [3]. Checkpoint signaling produces the "mitotic checkpoint complex" (MCC), which prevents anaphase by targeting Cdc20, the activator of the anaphase-promoting complex/cyclosome (APC/C). Recent biochemical and structural studies revealed that the human MCC binds two Cdc20 molecules, one (Cdc20(M)) through well-characterized, cooperative binding to Mad2 and Mad3/BubR1 (forming the "core MCC") and the other one (Cdc20(A)) through additional binding sequences in Mad3/BubR1 [4-6]...
April 24, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28358323/identification-of-a-ribose-phosphate-pyrophosphokinase-that-can-interact-in-vivo-with-the-anaphase-promoting-complex-cyclosome
#20
Haiyang Yu, Yu Zhang, Dong Zhang, Yanxi Lu, Haixia He, Fucong Zheng, Meng Wang
5-Phospho-d-ribosyl-1-diphosphate (PRPP) synthase (PRS) catalyzes the biosynthesis of PRPP, which is an important compound of metabolism in most organisms. However, no PRS genes have been cloned, let alone studied for their biological function in rubber tree. In this study, we identify a novel protein (PRS4) that interacts in vivo with rubber tree anaphase promoting complex/cyclosome (APC/C) subunit 10 (HbAPC10) by yeast two-hybrid assays. PRS4 has been cloned from rubber tree and named as HbPRS4. Blastp search in the genome of Arabidopsis thaliana showed that HbPRS4 shared the highest similarity with AtPRS4, with 80...
March 30, 2017: International Journal of Molecular Sciences
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