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Anaphase-promoting complex

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https://www.readbyqxmd.com/read/28401073/structural-insight-into-anaphase-promoting-complex-3-structure-and-docking-with-a-natural-inhibitory-compound
#1
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
#2
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 10, 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
#3
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
#4
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
#5
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]...
March 28, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28366743/different-functionality-of-cdc20-binding-sites-within-the-mitotic-checkpoint-complex
#6
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]...
March 28, 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
#7
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
https://www.readbyqxmd.com/read/28349831/cell-division-cycle-20-overexpression-predicts-poor-prognosis-for-patients-with-lung-adenocarcinoma
#8
Run Shi, Qi Sun, Jing Sun, Xin Wang, Wenjie Xia, Gaochao Dong, Anpeng Wang, Feng Jiang, Lin Xu
The cell division cycle 20, a key component of spindle assembly checkpoint, is an essential activator of the anaphase-promoting complex. Aberrant expression of cell division cycle 20 has been detected in various human cancers. However, its clinical significance has never been deeply investigated in non-small-cell lung cancer. By analyzing The Cancer Genome Atlas database and using some certain online databases, we validated overexpression of cell division cycle 20 in both messenger RNA and protein levels, explored its clinical significance, and evaluated the prognostic role of cell division cycle 20 in non-small-cell lung cancer...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28339487/nucleolar-asymmetry-and-the-importance-of-septin-integrity-upon-cell-cycle-arrest
#9
Urvashi Rai, Fadi Najm, Alan M Tartakoff
Cell cycle arrest can be imposed by inactivating the anaphase promoting complex (APC). In S. cerevisiae this arrest has been reported to stabilize a metaphase-like intermediate in which the nuclear envelope spans the bud neck, while chromatin repeatedly translocates between the mother and bud domains. The present investigation was undertaken to learn how other features of nuclear organization are affected upon depletion of the APC activator, Cdc20. We observe that the spindle pole bodies and the spindle repeatedly translocate across the narrow orifice at the level of the neck...
2017: PloS One
https://www.readbyqxmd.com/read/28336772/gmilpa1-encoding-an-anaphase-promoting-complex-like-protein-affects-leaf-petiole-angle
#10
Jinshan Gao, Suxin Yang, Weng Cheng, Yongfu Fu, Jiantian Leng, Xiaohui Yuan, Ning Jiang, Jianxin Ma, Xianzhong Feng
Leaf petiole angle is an important plant architectural trait that affects canopy coverage, photosynthetic efficiency, and ultimately productivity in many legume crops. However, the genetic basis underlying this trait remains unclear. Here, we report the identification, isolation, and functional characterization of Glycine max Increased Leaf Petiole Angle 1 (GmILPA1), a gene encoding an APC8-like protein, that is a subunit of the anaphase-promoting complex/cyclosome (APC/C) in soybean. A gamma ray-induced deletion of a fragment involving the 4th exon of GmILPA1 and its flanking sequences led to extension of the 3rd exon and formation of a novel 3'UTR from intronic and intergenic sequences...
March 23, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28322826/apc-cdh1-controls-cell-cycle-entry-during-liver-regeneration
#11
Ranran Cheng, Xin Liang, Quancheng Zhao, Zhusheng Lian, Lichun Tang, Chen Qiu, Huan Chen, Pumin Zhang
Cdh1 is one of the two adaptor proteins of anaphase-promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase controlling mitosis and DNA replication. To date, the in vivo functions of Cdh1 have not been fully explored. In order to characterize Cdh1 in liver regeneration, we generated a conditional knock-out mouse model. Our data showed that loss of Cdh1 leads to increased and extended S phase progression possibly due to the upregulation of cyclin D1. Moreover, the increased DNA replication resulted in activated DNA damage response...
March 18, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28298492/-wait-anaphase-signals-are-not-confined-to-the-mitotic-spindle
#12
Lydia Reńe Heasley, Steven M Markus, Jennifer G DeLuca
The Spindle Assembly Checkpoint ensures the faithful inheritance of chromosomes by arresting mitotic progression in the presence of kinetochores that are not attached to spindle microtubules. This is achieved through inhibition of the Anaphase Promoting Complex/Cyclosome by a kinetochore-derived 'wait anaphase' signal known as the Mitotic Checkpoint Complex. It remains unclear whether the localization and activity of these inhibitory complexes are restricted to the mitotic spindle compartment or are diffusible throughout the cytoplasm...
March 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28260026/ube2c-induces-emt-through-wnt-%C3%AE-%C3%A2-catenin-and-pi3k-akt-signaling-pathways-by-regulating-phosphorylation-levels-of-aurora-a
#13
Rui Wang, Yue Song, Xi Liu, Qixue Wang, Yunfei Wang, Liwei Li, Chunsheng Kang, Qingyu Zhang
The ubiquitin-conjugating enzyme 2C (UBE2C) is the key component in the ubiquitin proteasome system (UPS) by partnering with the anaphase‑promoting complex (APC/C). A high UBE2C protein expression level has been reported in various types of human tumors. However, little is known about the precise mechanism by which UBE2C expression is downregulated in gastric cancer. We found in MGC‑803 and SGC‑7901 gastric cancer cells UBE2C‑deficient G2/M phase arrest in the cell cycle and subsequently decreased gastric adenocarcinoma tumorigenesis...
April 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28257844/ube2s-associated-with-oscc-proliferation-by-promotion-of-p21-degradation-via-the-ubiquitin-proteasome-system
#14
Shusaku Yoshimura, Atsushi Kasamatsu, Dai Nakashima, Manabu Iyoda, Hiroki Kasama, Tomoaki Saito, Toshikazu Takahara, Yosuke Endo-Sakamoto, Masashi Shiiba, Hideki Tanzawa, Katsuhiro Uzawa
Ubiquitin-conjugating enzyme E2S (UBE2S), a family of E2 protein in the ubiquitin-proteasome system, is highly expressed in several types of cancers; however, its roles in oral squamous cell carcinoma (OSCC) have not yet been well elucidated. The purpose of this study was to clarify the functional activities of UBE2S in OSCCs. We analyzed the expression levels of UBE2S in nine OSCC cell lines and primary OSCC tissues by quantitative reverse transcriptase-polymerase chain reaction, Western blotting, and immunohistochemistry (IHC)...
April 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28228263/reciprocal-regulation-between-53bp1-and-the-anaphase-promoting-complex-cyclosome-is-required-for-genomic-stability-during-mitotic-stress
#15
Thomas J Kucharski, Paul E Minshall, Mohamed Moustafa-Kamal, Andrew S Turnell, Jose G Teodoro
The anaphase-promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase that targets substrates for degradation to promote mitotic progression. Here, we show that the DNA damage response protein 53BP1 contains conserved KEN boxes that are required for APC/C-dependent degradation in early mitosis. Mutation of the 53BP1 KEN boxes stabilized the protein and extended mitotic duration, whereas 53BP1 knockdown resulted in a shorter and delayed mitosis. Loss of 53BP1 increased APC/C activity, and we show that 53BP1 is a direct APC/C inhibitor...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28202332/cdc20-at-the-crossroads-between-chromosome-segregation-and-mitotic-exit
#16
REVIEW
Maria Kapanidou, Natalie L Curtis, Victor M Bolanos-Garcia
Cell-division cycle protein 20 homologue (Cdc20) has important functions in chromosome segregation and mitotic exit. Cdc20 is the target of the spindle assembly checkpoint (SAC) and a key cofactor of the anaphase-promoting complex or cyclosome (APC/C) E3 ubiquitin ligase, thus regulating APC/C ubiquitin activity on specific substrates for their subsequent degradation by the proteasome. Here we discuss the roles of Cdc20 in SAC signalling and mitotic exit, describe how the integration of traditional approaches with emerging technologies has revealed new details of Cdc20 functions, comment about the potential of Cdc20 as a therapeutic target for the treatment of human malignancies, and discuss recent advances and controversies in the mechanistic understanding of the control of chromosome segregation during cell division...
February 12, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28178520/identification-of-a-sgo2-dependent-but-mad2-independent-pathway-controlling-anaphase-onset-in-fission-yeast
#17
John C Meadows, Theresa C Lancaster, Graham J Buttrick, Alicja M Sochaj, Liam J Messin, Maria Del Mar Mora-Santos, Kevin G Hardwick, Jonathan B A Millar
The onset of anaphase is triggered by activation of the anaphase-promoting complex/cyclosome (APC/C) following silencing of the spindle assembly checkpoint (SAC). APC/C triggers ubiquitination of Securin and Cyclin B, which leads to loss of sister chromatid cohesion and inactivation of Cyclin B/Cdk1, respectively. This promotes relocalization of Aurora B kinase and other components of the chromosome passenger complex (CPC) from centromeres to the spindle midzone. In fission yeast, this is mediated by Clp1 phosphatase-dependent interaction of CPC with Klp9/MKLP2 (kinesin-6)...
February 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28167614/tuning-chromosomal-instability-to-optimize-tumor-fitness
#18
Mark E Burkard, Beth A Weaver
Low rates of chromosomal instability (CIN) are weakly tumor promoting, whereas high rates of CIN cause cell death and tumor suppression. In this context, Sansregret and colleagues show that one mechanism to restrain excessive CIN in tumor cells and increase fitness is through mutations in the anaphase promoting complex/cyclosome. This serves to delay mitotic progression and decrease the rate of chromosome missegregation. Cancer Discov; 7(2); 134-6. ©2017 AACRSee related article by Sansregret et al., p. 218...
February 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28143883/fzr1-loss-increases-sensitivity-to-dna-damage-and-consequently-promotes-murine-and-human-b-cell-acute-leukemia
#19
Jo Ishizawa, Eiji Sugihara, Shinji Kuninaka, Kaoru Mogushi, Kensuke Kojima, Christopher B Benton, Ran Zhao, Dhruv Chachad, Norisato Hashimoto, Rodrigo O Jacamo, Yihua Qiu, Suk Young Yoo, Shinichiro Okamoto, Michael Andreeff, Steven M Kornblau, Hideyuki Saya
FZR1 (fizzy-related protein homolog, also called CDH1, cell division cycle 20 related 1) functions in the cell cycle as a specific activator of APC/C (anaphase-promoting complex or cyclosome) ubiquitin ligase, regulating late mitosis, G1 phase and activation of the G2-M checkpoint. FZR1 has been implicated as both a tumor suppressor and oncoprotein, and its precise contribution to carcinogenesis remains unclear. Here, we examined the role of FZR1 in tumorigenesis and cancer therapy by analyzing tumor models and patient specimens...
January 31, 2017: Blood
https://www.readbyqxmd.com/read/28096334/role-of-cct-chaperonin-in-the-disassembly-of-mitotic-checkpoint-complexes
#20
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 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
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