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Anaphase-promoting complex

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...
October 17, 2016: Journal of the National Cancer Institute
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
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
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...
October 1, 2016: Biochimica et Biophysica Acta
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
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...
September 20, 2016: Molecular Reproduction and Development
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
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
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
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
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
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
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
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
Sarah M Beard, Ryan B Smit, Benjamin G Chan, Paul E Mains
After fertilization, rapid changes of the Caenorhabditis elegans cytoskeleton occur in the transition from meiosis to mitosis, requiring precise regulation. The MEI-1/MEI-2 katanin microtubule-severing complex is essential for meiotic spindle formation but must be quickly inactivated to allow for proper formation of the mitotic spindle. MEI-1/MEI-2 inactivation is dependent on multiple redundant pathways. The primary pathway employs the MEL-26 substrate adaptor for the CUL-3/cullin-based E3 ubiquitin ligase, which targets MEI-1 for proteosomal degradation...
October 13, 2016: G3: Genes—Genomes—Genetics
Masaya Yamaguchi, Ryan VanderLinden, Florian Weissmann, Renping Qiao, Prakash Dube, Nicholas G Brown, David Haselbach, Wei Zhang, Sachdev S Sidhu, Jan-Michael Peters, Holger Stark, Brenda A Schulman
The mitotic checkpoint complex (MCC) coordinates proper chromosome biorientation on the spindle with ubiquitination activities of CDC20-activated anaphase-promoting complex/cyclosome (APC/C(CDC20)). APC/C(CDC20) and two E2s, UBE2C and UBE2S, catalyze ubiquitination through distinct architectures for linking ubiquitin (UB) to substrates and elongating polyUB chains, respectively. MCC, which contains a second molecule of CDC20, blocks APC/C(CDC20)-UBE2C-dependent ubiquitination of Securin and Cyclins, while differentially determining or inhibiting CDC20 ubiquitination to regulate spindle surveillance, checkpoint activation, and checkpoint termination...
August 18, 2016: Molecular Cell
T Fuchsberger, S Martínez-Bellver, E Giraldo, V Teruel-Martí, A Lloret, J Viña
The E3 ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C) is activated by the fizzy-related protein homolog/CDC20-like protein 1 (cdh1) in post-mitotic neurons. Growing evidence suggests that dysregulation of APC/C-Cdh1 is involved in neurodegenerative diseases. Here we show in neurons that oligomers of amyloid beta (Aβ), a peptide related to Alzheimer's disease, cause proteasome-dependent degradation of cdh1. This leads to a subsequent increase in glutaminase (a degradation target of APC/C-Cdh1), which causes an elevation of glutamate levels and further intraneuronal Ca(2+) dysregulation, resulting in neuronal apoptosis...
2016: Scientific Reports
Claudio Alfieri, Leifu Chang, Ziguo Zhang, Jing Yang, Sarah Maslen, Mark Skehel, David Barford
In the dividing eukaryotic cell, the spindle assembly checkpoint (SAC) ensures that each daughter cell inherits an identical set of chromosomes. The SAC coordinates the correct attachment of sister chromatid kinetochores to the mitotic spindle with activation of the anaphase-promoting complex (APC/C), the E3 ubiquitin ligase responsible for initiating chromosome separation. In response to unattached kinetochores, the SAC generates the mitotic checkpoint complex (MCC), which inhibits the APC/C and delays chromosome segregation...
August 25, 2016: Nature
Hui Tang, Di Fan, Chun-Tao Lei, Chen Ye, Pan Gao, Shan Chen, Xian-Fang Meng, Hua Su, Chun Zhang
: The mitotic arrest deficient protein MAD2B is a well-defined anaphase-promoting complex/cyclosome (APC/C) inhibitor and a small subunit of DNA polymerase zeta. It is critical for mitotic control and DNA repair. However, the pathological role of MAD2B in kidney diseases has not been fully elucidated. In the present study, we aim to explore the role of MAD2B in the pathogenesis of renal tubulointerstitial fibrosis (TIF) and the underlying mechanism. By immunofluorescence and immunohistochemistry, we found an obvious MAD2B enhancement in tubular area of TIF patients and unilateral ureteral obstruction (UUO) mice...
August 3, 2016: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
Jia Liu, Lixin Wan, Jing Liu, Zhu Yuan, Jinfang Zhang, Jianfeng Guo, Marcos Malumbres, Jiankang Liu, Weiguo Zou, Wenyi Wei
Anaphase-promoting complex/cyclosome/Cdh1 is a multi-subunit ubiquitin E3 ligase that drives M to G1 cell cycle progression through primarily earmarking various substrates for ubiquitination and subsequent degradation by the 26S proteasome. Notably, emerging evidence suggested that Cdh1 could also function in various cellular processes independent of anaphase-promoting complex/cyclosome. To this end, we recently identified an anaphase-promoting complex/cyclosome-independent function of Cdh1 in modulating osteoblast differentiation through activating Smurf1, one of the NEDD4 family of HECT domain-containing E3 ligases...
2016: Cell Discovery
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