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Anaphase-promoting complex

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https://www.readbyqxmd.com/read/27903963/cdh1-regulates-e2f1-degradation-in-response-to-differentiation-signals-in-keratinocytes
#1
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
#2
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
#3
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...
November 11, 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
#4
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
#5
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
#6
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
#7
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
#8
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
https://www.readbyqxmd.com/read/27701050/s-nitroso-n-acetyl-penicillamine-inhibits-spontaneous-exit-from-metaphase-ii-arrest-in-rat-eggs-cultured-in-vitro
#9
Shilpa Prasad, Shail K Chaube
BACKGROUND: Present study was designed to investigate the in vitro effects of nitric oxide (NO) donor such as S-nitroso-N-acetyl penicillamine (SNAP) on spontaneous exit from metaphase-II arrest (SEM-II) in rat eggs cultured in vitro. METHODS: Ovulated eggs were denuded and then exposed to various concentrations (0.0, 0.01, 0.1 and 1.0mM) of SNAP for 3h under in vitro culture conditions. The percentage of SEM-II, specific and total phosphorylated cyclin-dependent kinase-1 (Cdk1), cyclin B1 and anaphase promoting complex/cyclosome (APC/C) levels as well as Cdk1 activity were analyzed...
October 1, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27693251/inhibition-of-cdk7-bypasses-spindle-assembly-checkpoint-via-premature-cyclin-b-degradation-during-oocyte-meiosis
#10
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
#11
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...
September 23, 2016: Molecular Biology Reports
https://www.readbyqxmd.com/read/27649288/analyses-of-emi-functions-on-meiotic-maturation-of-porcine-oocytes
#12
Yoshie A Fujioka, Asuka Onuma, Wataru Fujii, Koji Sugiura, Kunihiko Naito
Cyclin B (CCNB) accumulation is essential for regulating maturation/M-phase promoting factor activity during vertebrate oocyte maturation. Anaphase-promoting-complex/cyclosome (APC/C) degrades CCNB, allowing the cell cycle to progress; this complex is inhibited by Early mitotic inhibitors 1 and 2 (EMI1 and EMI2). The involvement of both EMI proteins in meiotic maturation has been reported in Xenopus and mouse oocytes, although a recent study described a marked difference in their respective function during meiotic resumption...
November 2016: Molecular Reproduction and Development
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
#13
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/27613041/detection-and-analysis-of-cell-cycle-associated-apc-c-mediated-cellular-ubiquitylation-in-vitro-and-in-vivo
#14
Cesyen Cedeño, Esther La Monaca, Mara Esposito, Gustavo J Gutierrez
The anaphase-promoting complex or cyclosome (APC/C) is one of the major orchestrators of the cell division cycle in mammalian cells. The APC/C acts as a ubiquitin ligase that triggers sequential ubiquitylation of a significant number of substrates which will be eventually degraded by proteasomes during major transitions of the cell cycle. In this chapter, we present accessible methodologies to assess both in in vitro conditions and in cellular systems ubiquitylation reactions mediated by the APC/C. In addition, we also describe techniques to evidence the changes in protein stability provoked by modulation of the activity of the APC/C...
2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27605379/the-btg4-and-caf1-complex-prevents-the-spontaneous-activation-of-eggs-by-deadenylating-maternal-mrnas
#15
Michał Pasternak, Sybille Pfender, Balaji Santhanam, Melina Schuh
Once every menstrual cycle, eggs are ovulated into the oviduct where they await fertilization. The ovulated eggs are arrested in metaphase of the second meiotic division, and only complete meiosis upon fertilization. It is crucial that the maintenance of metaphase arrest is tightly controlled, because the spontaneous activation of the egg would preclude the development of a viable embryo (Zhang et al. 2015 J. Genet. Genomics 42, 477-485. (doi:10.1016/j.jgg.2015.07.004); Combelles et al. 2011 Hum. Reprod. 26, 545-552...
September 2016: Open Biology
https://www.readbyqxmd.com/read/27601667/wd40-domain-of-apc1-is-critical-for-the-coactivator-induced-allosteric-transition-that-stimulates-apc-c-catalytic-activity
#16
Qiuhong Li, Leifu Chang, Shintaro Aibara, Jing Yang, Ziguo Zhang, David Barford
The anaphase-promoting complex/cyclosome (APC/C) is a large multimeric cullin-RING E3 ubiquitin ligase that orchestrates cell-cycle progression by targeting cell-cycle regulatory proteins for destruction via the ubiquitin proteasome system. The APC/C assembly comprises two scaffolding subcomplexes: the platform and the TPR lobe that together coordinate the juxtaposition of the catalytic and substrate-recognition modules. The platform comprises APC/C subunits Apc1, Apc4, Apc5, and Apc15. Although the role of Apc1 as an APC/C scaffolding subunit has been characterized, its specific functions in contributing toward APC/C catalytic activity are not fully understood...
September 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27591192/synergistic-inhibition-of-the-apc-c-by-the-removal-of-apc15-in-hct116-cells-lacking-ube2c
#17
Dimitriya H Garvanska, Marie Sofie Yoo Larsen, Jakob Nilsson
The spindle assembly checkpoint (SAC) inhibits the anaphase-promoting complex/cyclosome (APC/C) in response to unattached kinetochores by generating a diffusible inhibitor termed the mitotic checkpoint complex (MCC). At metaphase, rapid activation of the APC/C requires removal of the MCC, a process that has been shown to depend on the APC/C E2 enzymes, UBE2C and UBE2S. Here we investigate the in vivo role of the APC/C E2 enzymes in SAC silencing using CRISPR/Cas9 genetically engineered HCT116 UBE2C or UBE2S null cell lines...
October 15, 2016: Biology Open
https://www.readbyqxmd.com/read/27558644/targeting-of-fzr-cdh1-for-timely-activation-of-the-apc-c-at-the-centrosome-during-mitotic-exit
#18
Francesco Meghini, Torcato Martins, Xavier Tait, Kazuyuki Fujimitsu, Hiroyuki Yamano, David M Glover, Yuu Kimata
A multi-subunit ubiquitin ligase, the anaphase-promoting complex/cyclosome (APC/C), regulates critical cellular processes including the cell cycle. To accomplish its diverse functions, APC/C activity must be precisely regulated in time and space. The interphase APC/C activator Fizzy-related (Fzr or Cdh1) is localized at centrosomes in animal cells. However, neither the mechanism of its localization nor its importance is clear. Here we identify the centrosome component Spd2 as a major partner of Fzr in Drosophila...
2016: Nature Communications
https://www.readbyqxmd.com/read/27550197/transcript-levels-of-androgen-receptor-variant-7-and-ubiquitin-conjugating-enzyme-2c-in-hormone-sensitive-prostate-cancer-and-castration-resistant-prostate-cancer
#19
Chan Ho Lee, Ja Yoon Ku, Jung Min Ha, Sun Sik Bae, Jeong Zoo Lee, Choung-Soo Kim, Hong Koo Ha
PURPOSE: This study is designed to identify the androgen receptor variant 7 (AR-V7) status, clinical significance of AR-V7 in hormone sensitive prostate cancer (HSPC). Then, we evaluated AR-V7 and changes of its target gene, ubiquitin-conjugating enzyme E2C (UBE2C) which is an anaphase-promoting complex/cyclosome (APC/C)-specific ubiquitin-conjugating enzyme, in castration-resistant prostate cancer (CRPC) in serial tumor biopsies from patients receiving androgen deprivation therapy. METHODS: We used RT-PCR and Q-PCR assay to evaluate AR-V7, androgen receptor full length (AR-FL), and UBE2C in tumor biopsies from patients with HSPC and CRPC...
August 22, 2016: Prostate
https://www.readbyqxmd.com/read/27528370/superoxide-serves-as-a-putative-signal-molecule-for-plant-cell-division-overexpression-of-carlk1-promotes-the-plant-cell-cycle-via-accumulation-of-o2-and-decrease-in-h2-o2
#20
Dong Ju Lee, Hyun Jun Choi, Mid-Eum Moon, Youn-Tae Chi, Kon-Young Ji, Doil Choi
Reactive oxygen species (ROS) exert both positive and negative effects on plant growth and development and therefore receive a great deal of attention in current research. A hot pepper (Capsicum annuum) Receptor-like Kinase1 (CaRLK1) was ectopically expressed in N. tabacum BY-2 cell and N. benthamiana plants. This ectopic expression of CaRLK1 enhanced cell division and proliferation in both heterologous systems. Apparently, CaRLK1 was involved in controlling the cell cycle, possibly by inducing expressions of cyclin B1, cyclin D3, cyclin-dependent protein kinase 3, condensin complex subunit 2, and anaphase-promoting complex subunit 11 genes...
August 16, 2016: Physiologia Plantarum
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