scholarly journals ANAPHASE PROMOTING COMPLEX/CYCLOSOME-mediated cyclin B1 degradation is critical for cell cycle synchronization in syncytial endosperms

2018 ◽  
Vol 60 (6) ◽  
pp. 448-454 ◽  
Author(s):  
Lei Guo ◽  
Li Jiang ◽  
Xiu-Li Lu ◽  
Chun-Ming Liu
Keyword(s):  
Cell Cycle ◽  
Cyclin B1 ◽  
Anaphase Promoting Complex ◽  
Cell Cycle Synchronization

scholarly journals Nonperiodic Activity of the Human Anaphase-Promoting Complex–Cdh1 Ubiquitin Ligase Results in Continuous DNA Synthesis Uncoupled from Mitosis

2000 ◽  
Vol 20 (20) ◽  
pp. 7613-7623 ◽  
Author(s):  
Claus Storgaard Sørensen ◽  
Claudia Lukas ◽  
Edgar R. Kramer ◽  
Jan-Michael Peters ◽  
Jiri Bartek ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Dna Replication ◽  
Dna Synthesis ◽  
Ubiquitin Ligase ◽  
Mammalian Cells ◽  
Kinase Inhibitor ◽  
Cyclin B1 ◽  
S Phase ◽  
Anaphase Promoting Complex

ABSTRACT Ubiquitin-proteasome-mediated destruction of rate-limiting proteins is required for timely progression through the main cell cycle transitions. The anaphase-promoting complex (APC), periodically activated by the Cdh1 subunit, represents one of the major cellular ubiquitin ligases which, in Saccharomyces cerevisiae andDrosophila spp., triggers exit from mitosis and during G1 prevents unscheduled DNA replication. In this study we investigated the importance of periodic oscillation of the APC-Cdh1 activity for the cell cycle progression in human cells. We show that conditional interference with the APC-Cdh1 dissociation at the G1/S transition resulted in an inability to accumulate a surprisingly broad range of critical mitotic regulators including cyclin B1, cyclin A, Plk1, Pds1, mitosin (CENP-F), Aim1, and Cdc20. Unexpectedly, although constitutively assembled APC-Cdh1 also delayed G1/S transition and lowered the rate of DNA synthesis during S phase, some of the activities essential for DNA replication became markedly amplified, mainly due to a progressive increase of E2F-dependent cyclin E transcription and a rapid turnover of the p27Kip1 cyclin-dependent kinase inhibitor. Consequently, failure to inactivate APC-Cdh1 beyond the G1/S transition not only inhibited productive cell division but also supported slow but uninterrupted DNA replication, precluding S-phase exit and causing massive overreplication of the genome. Our data suggest that timely oscillation of the APC-Cdh1 ubiquitin ligase activity represents an essential step in coordinating DNA replication with cell division and that failure of mechanisms regulating association of APC with the Cdh1 activating subunit can undermine genomic stability in mammalian cells.

scholarly journals Differential expression, localization and activity of two alternatively spliced isoforms of human APC regulator CDH1

2003 ◽  
Vol 374 (2) ◽  
pp. 349-358 ◽  
Author(s):  
Yuan ZHOU ◽  
Yick-Pang CHING ◽  
Raymond W. M. NG ◽  
Dong-Yan JIN
Keyword(s):  
Cell Cycle ◽  
Differential Expression ◽  
Cultured Cells ◽  
Cyclin A ◽  
Cyclin B1 ◽  
Anaphase Promoting Complex ◽  
Cycle Arrest ◽  
Localization Signal ◽  
Alternatively Spliced

The timely destruction of key regulators through ubiquitin-mediated proteolysis ensures the orderly progression of the cell cycle. The APC (anaphase-promoting complex) is a major component of this degradation machinery and its activation is required for the execution of critical events. Recent studies have just begun to reveal the complex control of the APC through a regulatory network involving WD40 repeat proteins CDC20 and CDH1. In the present paper, we report on the identification and characterization of human CDH1β, a novel alternatively spliced isoform of CDH1. Both CDH1α and CDH1β can bind to the APC and stimulate the degradation of cyclin B1, but they are differentially expressed in human tissues and cells. CDH1α contains a nuclear localization signal which is absent in CDH1β. Intracellularly, CDH1α appears in the nucleus whereas CDH1β is a predominantly cytoplasmic protein. The forced overexpression of CDH1α in cultured cells correlates with the reduction of nuclear cyclin A, but the steady-state amount of cyclin A does not change noticeably in CDH1β-overexpressed cells. In Xenopus embryos, ectopic overexpression of human CDH1α, but not of CDH1β, induces cell-cycle arrest during the first G1 phase at the mid-blastula transition. Taken together, our findings document the differential expression, subcellular localization and cell-cycle-regulatory activity of human CDH1 isoforms.

scholarly journals Mammalian egg activation: from Ca2+ spiking to cell cycle progression

Reproduction ◽  
2005 ◽  
Vol 130 (6) ◽  
pp. 813-823 ◽  
Author(s):  
Keith T Jones
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Polar Body ◽  
Signal Transduction Pathway ◽  
Cyclin B1 ◽  
Egg Activation ◽  
Anaphase Promoting Complex ◽  
Sister Chromatids ◽  
Dependent Protein ◽  
Second Polar Body

Mammalian eggs arrest at metaphase of the second meiotic division (MetII). Sperm break this arrest by inducing a series of Ca2+spikes that last for several hours. During this time cell cycle resumption is induced, sister chromatids undergo anaphase and the second polar body is extruded. This is followed by decondensation of the chromatin and the formation of pronuclei. Ca2+spiking is both the necessary and solely sufficient sperm signal to induce full egg activation. How MetII arrest is established, how the Ca2+spiking is induced and how the signal is transduced into cell cycle resumption are the topics of this review. Although the roles of most components of the signal transduction pathway remain to be fully investigated, here I present a model in which a sperm-specific phospholipase C (PLCζ) generates Ca2+spikes to activate calmodulin-dependent protein kinase II and so switch on the Anaphase-Promoting Complex/Cyclosome (APC/C). APC/C activation leads to securin and cyclin B1 degradation and in so doing allows sister chromatids to be segregated and to decondense.

scholarly journals Glypican-1 Regulates Anaphase Promoting Complex/Cyclosome Substrates and Cell Cycle Progression in Endothelial Cells

2008 ◽  
Vol 19 (7) ◽  
pp. 2789-2801 ◽  
Author(s):  
Dianhua Qiao ◽  
Xinhai Yang ◽  
Kristy Meyer ◽  
Andreas Friedl
Keyword(s):  
Cell Cycle ◽  
Endothelial Cells ◽  
Cell Cycle Progression ◽  
Cyclin B1 ◽  
Anaphase Promoting Complex ◽  
Cycle Progression ◽  
Cycle Arrest ◽  
Flow Cytometric ◽  
Biochemical Analyses

Glypican-1 (GPC1), a member of the mammalian glypican family of heparan sulfate proteoglycans, is highly expressed in glioma blood vessel endothelial cells (ECs). In this study, we investigated the role of GPC1 in EC replication by manipulating GPC1 expression in cultured mouse brain ECs. Moderate GPC1 overexpression stimulates EC growth, but proliferation is significantly suppressed when GPC1 expression is either knocked down or the molecule is highly overexpressed. Flow cytometric and biochemical analyses show that high or low expression of GPC1 causes cell cycle arrest at mitosis or the G2 phase of the cell cycle, accompanied by endoreduplication and consequently polyploidization. We further show that GPC1 inhibits the anaphase-promoting complex/cyclosome (APC/C)–mediated degradation of mitotic cyclins and securin. High levels of GPC1 induce metaphase arrest and centrosome overproduction, alterations that are mimicked by overexpression of cyclin B1 and cyclin A, respectively. These observations suggest that GPC1 regulates EC cell cycle progression at least partially by modulating APC/C-mediated degradation of mitotic cyclins and securin.

Cyclin B1 transcription is enhanced by the p300 coactivator and regulated during the cell cycle by a CHR-dependent repression mechanism

FEBS Letters ◽  
2003 ◽  
Vol 536 (1-3) ◽  
pp. 66-70 ◽  
Author(s):  
Mark Wasner ◽  
Katrin Tschöp ◽  
Katja Spiesbach ◽  
Ulrike Haugwitz ◽  
Cindy Johne ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cyclin B1

scholarly journals The Role of Cdh1p in Maintaining Genomic Stability in Budding Yeast

Genetics ◽  
2003 ◽  
Vol 165 (2) ◽  
pp. 489-503 ◽  
Author(s):  
Karen E Ross ◽  
Orna Cohen-Fix
Keyword(s):  
Cell Cycle ◽  
Chromosome Segregation ◽  
Spindle Assembly Checkpoint ◽  
Chromosome Loss ◽  
Cyclin Dependent Kinase ◽  
Anaphase Promoting Complex ◽  
Growth Defects ◽  
Genes Encoding ◽  
Specificity Factor

Abstract Cdh1p, a substrate specificity factor for the cell cycle-regulated ubiquitin ligase, the anaphase-promoting complex/cyclosome (APC/C), promotes exit from mitosis by directing the degradation of a number of proteins, including the mitotic cyclins. Here we present evidence that Cdh1p activity at the M/G1 transition is important not only for mitotic exit but also for high-fidelity chromosome segregation in the subsequent cell cycle. CDH1 showed genetic interactions with MAD2 and PDS1, genes encoding components of the mitotic spindle assembly checkpoint that acts at metaphase to prevent premature chromosome segregation. Unlike cdh1Δ and mad2Δ single mutants, the mad2Δ cdh1Δ double mutant grew slowly and exhibited high rates of chromosome and plasmid loss. Simultaneous deletion of PDS1 and CDH1 caused extensive chromosome missegregation and cell death. Our data suggest that at least part of the chromosome loss can be attributed to kinetochore/spindle problems. Our data further suggest that Cdh1p and Sic1p, a Cdc28p/Clb inhibitor, have overlapping as well as nonoverlapping roles in ensuring proper chromosome segregation. The severe growth defects of both mad2Δ cdh1Δ and pds1Δ cdh1Δ strains were rescued by overexpressing Swe1p, a G2/M inhibitor of the cyclin-dependent kinase, Cdc28p/Clb. We propose that the failure to degrade cyclins at the end of mitosis leaves cdh1Δ mutant strains with abnormal Cdc28p/Clb activity that interferes with proper chromosome segregation.

Cell Cycle Synchronization of the Murine EO771 Cell Line Using Double Thymidine Block Treatment

BioEssays ◽  
2020 ◽  
Vol 42 (9) ◽  
pp. 1900116
Author(s):  
Marie Goepp ◽  
Delphine Le Guennec ◽  
Adrien Rossary ◽  
Marie‐Paule Vasson
Keyword(s):  
Cell Cycle ◽  
Cell Line ◽  
Cell Cycle Synchronization
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