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Anaphase-promoting complex

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https://www.readbyqxmd.com/read/28096334/role-of-cct-chaperonin-in-the-disassembly-of-mitotic-checkpoint-complexes
#1
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 17, 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
#2
Zhejian Ji, Haishan Gao, Luying Jia, Bing Li, Hongtao Yu
The master spindle checkpoint kinase Mps1 directly 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/28069571/apc-c-dysfunction-limits-excessive-cancer-chromosomal-instability
#3
Laurent Sansregret, James O Patterson, Sally Dewhurst, Carlos López-García, André Koch, Nicholas McGranahan, William Chong Hang Chao, David J Barry, Andrew Rowan, Rachael Instrell, Stuart Horswell, Michael Way, Michael Howell, Martin R Singleton, René H Medema, Paul Nurse, Mark Petronczki, Charles Swanton
: Intercellular heterogeneity, exacerbated by chromosomal instability (CIN), fosters tumor heterogeneity and drug resistance. However, extreme CIN correlates with improved cancer outcome, suggesting that karyotypic diversity required to adapt to selection pressures might be balanced in tumors against the risk of excessive instability. Here, we used a functional genomics screen, genome editing, and pharmacologic approaches to identify CIN-survival factors in diploid cells. We find partial anaphase-promoting complex/cyclosome (APC/C) dysfunction lengthens mitosis, suppresses pharmacologically induced chromosome segregation errors, and reduces naturally occurring lagging chromosomes in cancer cell lines or following tetraploidization...
January 9, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28069132/molecular-regulation-of-the-spindle-assembly-checkpoint-by-kinases-and-phosphatases
#4
G Manic, F Corradi, A Sistigu, S Siteni, I Vitale
The spindle assembly checkpoint (SAC) is a surveillance mechanism contributing to the preservation of genomic stability by monitoring the microtubule attachment to, and/or the tension status of, each kinetochore during mitosis. The SAC halts metaphase to anaphase transition in the presence of unattached and/or untensed kinetochore(s) by releasing the mitotic checkpoint complex (MCC) from these improperly-oriented kinetochores to inhibit the anaphase-promoting complex/cyclosome (APC/C). The reversible phosphorylation of a variety of substrates at the kinetochore by antagonistic kinases and phosphatases is one major signaling mechanism for promptly turning on or turning off the SAC...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28059125/neuronal-apoptosis-inhibitory-protein-naip-localizes-to-the-cytokinetic-machinery-during-cell-division
#5
Francisco Abadía-Molina, Virginia Morón-Calvente, Stephen D Baird, Fahad Shamim, Francisco Martín, Alex MacKenzie
The neuronal apoptosis inhibitory protein (NAIP) is a constituent of the inflammasome and a key component of the innate immune system. Here we use immunofluorescence to position NAIP within the cytokinetic apparatus, contiguous to chromosomal passenger complex (CPC), Centralspindlin, PRC1 and KIF4A. During metaphase, NAIP accumulates in the mitotic spindle poles and is shown in spindle microtubules; in anaphase NAIP is detected in the middle of the central spindle. At the end of cytokinesis, NAIP is localized in the outlying region of the stem body, the center of the intercellular bridge formed between daughter cells prior to cellular abscission...
January 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28041906/apc-c-fzr-cdh1-dependent-regulation-of-planar-cell-polarity-establishment-via-nek2-kinase-acting-on-dishevelled
#6
Ursula Weber, Marek Mlodzik
The Anaphase-Promoting Complex/Cyclosome (APC/C) is an E3 ubiquitin ligase, well known for its role in cell-cycle progression. However, it has been linked to additional functions, mainly in neuronal contexts, when using the co-activator Cdh1/Fzr. Here, our data indicate a post-mitotic requirement for the APC/C(Fzr/Cdh1) in epithelial cell patterning and planar cell polarity (PCP) in Drosophila. PCP signaling is critical for development by establishing cellular asymmetries and orientation within the plane of an epithelium, via differential localization of distinct complexes of core PCP factors...
January 9, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28041905/the-apc-c-coordinates-retinal-differentiation-with-g1-arrest-through-the-nek2-dependent-modulation-of-wingless-signaling
#7
Torcato Martins, Francesco Meghini, Francesca Florio, Yuu Kimata
The cell cycle is coordinated with differentiation during animal development. Here we report a cell-cycle-independent developmental role for a master cell-cycle regulator, the anaphase-promoting complex or cyclosome (APC/C), in the regulation of cell fate through modulation of Wingless (Wg) signaling. The APC/C controls both cell-cycle progression and postmitotic processes through ubiquitin-dependent proteolysis. Through an RNAi screen in the developing Drosophila eye, we found that partial APC/C inactivation severely inhibits retinal differentiation independently of cell-cycle defects...
January 9, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28017606/generation-of-a-spindle-checkpoint-arrest-from-synthetic-signaling-assemblies
#8
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/28004426/inhibition-of-anaphase-promoting-complex-by-silence-apc-ccdh1to-enhance-radiosensitivity-of-nasopharyngeal-carcinoma-cells
#9
Chunmiao Wang, Zhengying Su, Huaxin Hou, Danrong Li, Zhiyu Pan, Wei Tian, Chunyan Mo
The aim of this study was to investigate the possibility of APC/C(Cdh1) as a potential therapeutic target in the radiosensitivity of nasopharyngeal carcinoma(NPC) cell CNE-1, and explain the role of APC subunits after silence of Cdh1 combined with radiotherapy. Transfection with Cdh1 shRNA significantly increased the radiosensitivity of CNE-1 cells and the radiation enhancement ratio (RER) of sh-Cdh1 cells was 1.76. Knockdown of Cdh1 in CNE-1 cells increased irradiation induced apoptosis and G2/M phase cell cycle arrest...
December 22, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27991546/apc-c-cdc20-and-apc-c-play-pivotal-roles-in-the-process-of-embryonic-development-in-artemia-sinica
#10
Mengchen Zhang, Feng Yao, Hong Luan, Wei Zhao, Ting Jing, Shuang Zhang, Lin Hou, Xiangyang Zou
Anaphase Promoting Complex or Cyclosome (APC/C) is a representative E3 ubiquitin ligase, triggering the transition of metaphase to anaphase by regulating degradation and ensures the exit from mitosis. Cell division cycle 20 (CDC20) and Cell division cycle 20 related protein 1 (CDH1), as co-activators of APC/C, play significant roles in the spindle assembly checkpoint, guiding ubiquitin-mediated degradation, together with CDC23. During the embryonic development of the brine shrimp, Artemia sinica, CDC20, CDH1 and CDC23 participate in cell cycle regulation, but the specific mechanisms of their activities remain unknown...
December 19, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27939943/the-mitotic-checkpoint-complex-requires-an-evolutionary-conserved-cassette-to-bind-and-inhibit-active-apc-c
#11
Barbara Di Fiore, Claudia Wurzenberger, Norman E Davey, Jonathon Pines
The Spindle Assembly Checkpoint (SAC) ensures genomic stability by preventing sister chromatid separation until all chromosomes are attached to the spindle. It catalyzes the production of the Mitotic Checkpoint Complex (MCC), which inhibits Cdc20 to inactivate the Anaphase Promoting Complex/Cyclosome (APC/C). Here we show that two Cdc20-binding motifs in BubR1 of the recently identified ABBA motif class are crucial for the MCC to recognize active APC/C-Cdc20. Mutating these motifs eliminates MCC binding to the APC/C, thereby abolishing the SAC and preventing cells from arresting in response to microtubule poisons...
December 15, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27932423/integrated-genomic-analysis-of-survival-outliers-in-glioblastoma
#12
Sen Peng, Harshil Dhurv, Brock Armstrong, Bodour Salhia, Christophe Legendre, Jeffrey Kiefer, Julianna Parks, Selene Virk, Andrew E Sloan, Quinn T Ostrom, Jill S Barnholtz-Sloan, Nhan L Tran, Michael E Berens
BACKGROUND: To elucidate molecular features associated with disproportionate survival of glioblastoma (GB) patients, we conducted deep genomic comparative analysis of a cohort of patients receiving standard therapy (surgery plus concurrent radiation and temozolomide); "GB outliers" were identified: long-term survivor of 33 months (LTS; n = 8) versus short-term survivor of 7 months (STS; n = 10). METHODS: We implemented exome, RNA, whole genome sequencing, and DNA methylation for collection of deep genomic data from STS and LTS GB patients...
December 8, 2016: Neuro-oncology
https://www.readbyqxmd.com/read/27903963/cdh1-regulates-e2f1-degradation-in-response-to-differentiation-signals-in-keratinocytes
#13
Randeep K Singh, Lina Dagnino
The E2F1 transcription factor plays key roles in skin homeostasis. In the epidermis, E2F1 expression is essential for normal proliferation of undifferentiated keratinocytes, regeneration after injury and DNA repair following UV radiation-induced photodamage. Abnormal E2F1 expression promotes nonmelanoma skin carcinoma. In addition, E2F1 must be downregulated for proper keratinocyte differentiation, but the relevant mechanisms involved remain poorly understood. We show that differentiation signals induce a series of post-translational modifications in E2F1 that are jointly required for its downregulation...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27893964/aneuploidy-in-cancer-and-aging
#14
Ryan M Naylor, Jan M van Deursen
Chromosomal instability (CIN), the persistent inability of a cell to faithfully segregate its genome, is a feature of many cancer cells. It stands to reason that CIN enables the acquisition of multiple cancer hallmarks; however, there is a growing body of evidence suggesting that CIN impairs cellular fitness and prevents neoplastic transformation. Here, we suggest a new perspective to reconcile this apparent paradox and share an unexpected link between aneuploidy and aging that was discovered through attempts to investigate the CIN-cancer relationship...
November 23, 2016: Annual Review of Genetics
https://www.readbyqxmd.com/read/27889750/metformin-protects-neurons-against-oxygen-glucose-deprivation-reoxygenation-induced-injury-by-down-regulating-mad2b
#15
Xianfang Meng, Guangpin Chu, Zhihua Yang, Ping Qiu, Yue Hu, Xiaohe Chen, Wenpeng Peng, Chen Ye, Fang-Fang He, Chun Zhang
BACKGROUND/AIMS: Metformin, the common medication for type II diabetes, has protective effects on cerebral ischemia. However, the molecular mechanisms are far from clear. Mitotic arrest deficient 2-like protein 2 (MAD2B), an inhibitor of the anaphase-promoting complex (APC), is widely expressed in hippocampal and cortical neurons and plays an important role in mediating high glucose-induced neurotoxicity. The present study investigated whether metformin modifies the expression of MAD2B and to exert its neuroprotective effects in primary cultured cortical neurons during oxygen-glucose deprivation/reoxygenation (OGD/R), a widely used in vitro model of ischemia/reperfusion...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27810909/the-ubiquitin-ligase-crl2zyg11-targets-cyclin-b1-for-degradation-in-a-conserved-pathway-that-facilitates-mitotic-slippage
#16
Riju S Balachandran, Cassandra S Heighington, Natalia G Starostina, James W Anderson, David L Owen, Srividya Vasudevan, Edward T Kipreos
The anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase is known to target the degradation of cyclin B1, which is crucial for mitotic progression in animal cells. In this study, we show that the ubiquitin ligase CRL2(ZYG-11) redundantly targets the degradation of cyclin B1 in Caenorhabditis elegans and human cells. In C. elegans, both CRL2(ZYG-11) and APC/C are required for proper progression through meiotic divisions. In human cells, inactivation of CRL2(ZYG11A/B) has minimal effects on mitotic progression when APC/C is active...
October 24, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27810907/slip-slidin-away-of-mitosis-with-crl2zyg11
#17
Michael Brandeis
The spindle assembly checkpoint arrests mitotic cells by preventing degradation of cyclin B1 by the anaphase-promoting complex/cyclosome, but some cells evade this checkpoint and slip out of mitosis. Balachandran et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201601083) show that the E3 ligase CRL2(ZYG11) degrades cyclin B1, allowing mitotic slippage.
October 24, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27797072/biochemical-and-functional-assays-of-human-cohesin-releasing-factor-wapl
#18
Ge Zheng, Zhuqing Ouyang, Hongtao Yu
During the cell cycle, duplicated sister chromatids become physically connected during S phase through a process called sister-chromatid cohesion. Cohesion is terminated during the metaphase-to-anaphase transition to trigger sister-chromatid segregation. The establishment and dissolution of cohesion are highly regulated by the cohesin complex and its multitude of regulators. In particular, the cohesin regulator Wapl promotes the release of cohesin from chromosomes during both interphase and mitosis. Here, we describe in vitro protein binding assays between Wapl and a cohesin subcomplex, and cellular assays in human cells that probe the functions of Wapl in cohesin release...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27754928/association-of-uba6-specific-e2-use1-with-lung-tumorigenesis
#19
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 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/27716480/building-a-regulatory-network-with-short-linear-sequence-motifs-lessons-from-the-degrons-of-the-anaphase-promoting-complex
#20
REVIEW
Norman E Davey, David O Morgan
The anaphase-promoting complex or cyclosome (APC/C) is a ubiquitin ligase that polyubiquitinates specific substrates at precise times in the cell cycle, thereby triggering the events of late mitosis in a strict order. The robust substrate specificity of the APC/C prevents the potentially deleterious degradation of non-APC/C substrates and also averts the cell-cycle errors and genomic instability that could result from mistimed degradation of APC/C targets. The APC/C recognizes short linear sequence motifs, or degrons, on its substrates...
October 6, 2016: Molecular Cell
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