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Anaphase-promoting complex

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https://www.readbyqxmd.com/read/28807996/klhl6-deficiency-impairs-transitional-b-cell-survival-and-differentiation
#1
Barbara Bertocci, Damiana Lecoeuche, Delphine Sterlin, Julius Kühn, Baptiste Gaillard, Annie De Smet, Frederique Lembo, Christine Bole-Feysot, Nicolas Cagnard, Tatiana Fadeev, Auriel Dahan, Jean-Claude Weill, Claude-Agnès Reynaud
Klhl6 belongs to the KLHL gene family, which is composed of an N-terminal BTB-POZ domain and four to six Kelch motifs in tandem. Several of these proteins function as adaptors of the Cullin3 E3 ubiquitin ligase complex. In this article, we report that Klhl6 deficiency induces, as previously described, a 2-fold reduction in mature B cells. However, we find that this deficit is centered on the inability of transitional type 1 B cells to survive and to progress toward the transitional type 2 B cell stage, whereas cells that have passed this step generate normal germinal centers (GCs) upon a T-dependent immune challenge...
August 14, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28776765/s-cerevisiae-gle2-rae1-is-involved-in-septin-organization-essential-for-cell-cycle-progression
#2
Gesa Zander, Wilfried Kramer, Anika Seel, Heike Krebber
Gle2/Rae1 is highly conserved from yeast to humans and described as an mRNA export factor. Additionally, it is implicated in the anaphase-promoting complex (APC)-mediated cell cycle regulation in higher eukaryotes. Here we identified an involvement for S. cerevisiae Gle2 in septin organization, which is crucial for cell cycle progression and cell division. Gle2 genetically and physically interacts with components of the septin-ring. Importantly, deletion of GLE2 leads to elongated buds, severe defects in septin-assembly and their cellular mislocalization...
August 4, 2017: Yeast
https://www.readbyqxmd.com/read/28729434/cohesins-and-condensins-orchestrate-the-4d-dynamics-of-yeast-chromosomes-during-the-cell%C3%A2-cycle
#3
Luciana Lazar-Stefanita, Vittore F Scolari, Guillaume Mercy, Héloise Muller, Thomas M Guérin, Agnès Thierry, Julien Mozziconacci, Romain Koszul
Duplication and segregation of chromosomes involves dynamic reorganization of their internal structure by conserved architectural proteins, including the structural maintenance of chromosomes (SMC) complexes cohesin and condensin. Despite active investigation of the roles of these factors, a genome-wide view of dynamic chromosome architecture at both small and large scale during cell division is still missing. Here, we report the first comprehensive 4D analysis of the higher-order organization of the Saccharomyces cerevisiae genome throughout the cell cycle and investigate the roles of SMC complexes in controlling structural transitions...
July 20, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28711931/apc-c-is-essential-for-hematopoiesis-and-impaired-in-aplastic-anemia
#4
Jia Wang, Min-Zhi Yin, Ke-Wen Zhao, Fang Ke, Wen-Jie Jin, Xiao-Lin Guo, Tian-Hui Liu, Xiao-Ye Liu, Hao Gu, Xiao-Min Yu, Zhen Li, Li-Li Mu, Deng-Li Hong, Jing Chen, Guo-Qiang Chen
Anaphase promoting complex/cyclosome (APC/C) is essential for cell cycle progression. Recently, its non-mitotic functions were also reported but less studied in several tissues including hematopoietic cells. Here, we developed an inducible Anapc2 (a core subunit of APC/C) knockout mice. The animals displayed a fatal bone marrow failure within 7 days after knockout induction. Their hematopoietic stem and progenitor cells (HSPCs) demonstrated a sharp decline and could form little colony. Further, the results of BrdU label-retaining cell assay showed that the dormant HPSCs lost rapidly...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28711656/upregulation-of-cdh1-signaling-in-the-hippocampus-attenuates-brain-damage-after-transient-global-cerebral-ischemia-in-rats
#5
Bo Zhang, Kai Wei, Xuan Li, Rong Hu, Jin Qiu, Yue Zhang, Wenlong Yao, Chuanhan Zhang, Chang Zhu
Cerebral ischemia is a major cause of brain dysfunction. The E3 ubiquitin ligase anaphase-promoting complex and its coactivator Cdh1 have been reported to be involved in the regulation of neuronal survival, differentiation, axonal growth and synaptic development in the central nervous system. However, its role in the ischemic brain and the underlying mechanisms remain poorly understood. The present study aimed to investigate the effects of Cdh1 overexpression on the ischemic rat brain by direct intra-hippocampal injection of lentivirus-delivered Cdh1 before transient global cerebral ischemia reperfusion...
July 12, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28701343/let-99-functions-in-the-astral-furrowing-pathway-where-it-is-required-for-myosin-enrichment-in-the-contractile-ring
#6
Kari L Price, Lesilee S Rose
The anaphase spindle determines the position of the cytokinesis furrow, such that the contractile ring assembles in an equatorial zone between the two spindle poles. Contractile ring formation is mediated by RhoA activation at the equator by the centralspindlin complex and midzone microtubules. Astral microtubules also inhibit RhoA accumulation at the poles. In the C. elegans one-cell embryo, the astral microtubule dependent pathway requires anillin, NOP-1 and LET-99. LET-99 is well characterized for generating the asymmetric cortical localization of the Gα-dependent force-generating complex that positions the spindle during asymmetric division...
July 12, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28698355/tissue-specific-control-of-the-endocycle-by-the-anaphase-promoting-complex-cyclosome-inhibitors-uvi4-and-del1
#7
Jefri Heyman, Stefanie Polyn, Thomas Eekhout, Lieven De Veylder
The endocycle represents a modified mitotic cell cycle that in plants is often coupled to cell enlargement and differentiation. Endocycle onset is controlled by activity of the Anaphase Promoting Complex/Cyclosome (APC/C), a multi-subunit E3 ubiquitin ligase targeting cell cycle factors for destruction. CELL CYCLE SWITCH 52 (CCS52) proteins represent rate-limiting activator subunits of the APC/C. In Arabidopsis thaliana (Arabidopsis), mutations in either CCS52A1 or CCS52A2 activators result in a delayed endocycle onset, whereas their overexpression triggers increased DNA ploidy levels...
July 11, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28698300/kinetochores-accelerate-or-delay-apc-c-activation-by-directing-cdc20-to-opposing-fates
#8
Taekyung Kim, Pablo Lara-Gonzalez, Bram Prevo, Franz Meitinger, Dhanya K Cheerambathur, Karen Oegema, Arshad Desai
Mitotic duration is determined by activation of the anaphase-promoting complex/cyclosome (APC/C) bound to its coactivator, Cdc20. Kinetochores, the microtubule-interacting machines on chromosomes, restrain mitotic exit when not attached to spindle microtubules by generating a Cdc20-containing complex that inhibits the APC/C. Here, we show that flux of Cdc20 through kinetochores also accelerates mitotic exit by promoting its dephosphorylation by kinetochore-localized protein phosphatase 1, which allows Cdc20 to activate the APC/C...
June 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28678757/the-therapeutic-potential-of-cell-cycle-targeting-in-multiple-myeloma
#9
REVIEW
Anke Maes, Eline Menu, Kim De Veirman, Ken Maes, Karin Vanderkerken, Elke De Bruyne
Proper cell cycle progression through the interphase and mitosis is regulated by coordinated activation of important cell cycle proteins (including cyclin-dependent kinases and mitotic kinases) and several checkpoint pathways. Aberrant activity of these cell cycle proteins and checkpoint pathways results in deregulation of cell cycle progression, which is one of the key hallmarks of cancer. Consequently, intensive research on targeting these cell cycle regulatory proteins identified several candidate small molecule inhibitors that are able to induce cell cycle arrest and even apoptosis in cancer cells...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28667270/fam64a-is-a-novel-cell-cycle-promoter-of-hypoxic-fetal-cardiomyocytes-in-mice
#10
Ken Hashimoto, Aya Kodama, Takeshi Honda, Akira Hanashima, Yoshihiro Ujihara, Takashi Murayama, Shin-Ichiro Nishimatsu, Satoshi Mohri
Fetal cardiomyocytes actively proliferate to form the primitive heart in utero in mammals, but they stop dividing shortly after birth. The identification of essential molecules maintaining this active cardiomyocyte proliferation is indispensable for potential adult heart regeneration. A recent study has shown that this proliferation depends on a low fetal oxygen condition before the onset of breathing at birth. We have established an isolation protocol for mouse fetal cardiomyocytes, performed under strict low oxygen conditions to mimic the intrauterine environment, that gives the highest proliferative activities thus far reported...
June 30, 2017: Scientific Reports
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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