scholarly journals The Role of Anaphase-Promoting Complex/Cyclosome (APC/C) in Plant Reproduction

2021 ◽  
Vol 12 ◽  
Author(s):  
Marina de Lyra Soriano Saleme ◽  
Ingrid Rocha Andrade ◽  
Nubia Barbosa Eloy
Keyword(s):  
Chromosome Segregation ◽  
Ubiquitin Ligase ◽  
Male Gametophyte ◽  
Functional Characterization ◽  
E3 Ubiquitin Ligase ◽  
Embryo Sac ◽  
Anaphase Promoting Complex ◽  
Ploidy Stability ◽  
Embryo Sac Formation

Most eukaryotic species propagate through sexual reproduction that requires male and female gametes. In flowering plants, it starts through a single round of DNA replication (S phase) and two consecutive chromosome segregation (meiosis I and II). Subsequently, haploid mitotic divisions occur, which results in a male gametophyte (pollen grain) and a female gametophyte (embryo sac) formation. In order to obtain viable gametophytes, accurate chromosome segregation is crucial to ensure ploidy stability. A precise gametogenesis progression is tightly regulated in plants and is controlled by multiple mechanisms to guarantee a correct evolution through meiotic cell division and sexual differentiation. In the past years, research in the field has shown an important role of the conserved E3-ubiquitin ligase complex, Anaphase-Promoting Complex/Cyclosome (APC/C), in this process. The APC/C is a multi-subunit complex that targets proteins for degradation via proteasome 26S. The functional characterization of APC/C subunits in Arabidopsis, which is one of the main E3 ubiquitin ligase that controls cell cycle, has revealed that all subunits investigated so far are essential for gametophytic development and/or embryogenesis.

scholarly journals Role of ubiquitylation of components of mitotic checkpoint complex in their dissociation from anaphase-promoting complex/cyclosome

2018 ◽  
Vol 115 (8) ◽  
pp. 1777-1782 ◽  
Author(s):  
Danielle Sitry-Shevah ◽  
Sharon Kaisari ◽  
Adar Teichner ◽  
Shirly Miniowitz-Shemtov ◽  
Avram Hershko
Keyword(s):  
Chromosome Segregation ◽  
Ubiquitin Ligase ◽  
Mitotic Spindle ◽  
Mitotic Checkpoint ◽  
Terminal Region ◽  
Anaphase Promoting Complex ◽  
Lysine Residues ◽  
Mitotic Checkpoint Complex

The mitotic checkpoint system ensures the fidelity of chromosome segregation in mitosis by preventing premature initiation of anaphase until correct bipolar attachment of chromosomes to the mitotic spindle is reached. It promotes the assembly of a mitotic checkpoint complex (MCC), composed of BubR1, Bub3, Cdc20, and Mad2, which inhibits the activity of the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase. When the checkpoint is satisfied, anaphase is initiated by the disassembly of MCC. Previous studies indicated that the dissociation of APC/C-bound MCC requires ubiquitylation and suggested that the target of ubiquitylation is the Cdc20 component of MCC. However, it remained unknown how ubiquitylation causes the release of MCC from APC/C and its disassembly and whether ubiquitylation of additional proteins is involved in this process. We find that ubiquitylation causes the dissociation of BubR1 from Cdc20 in MCC and suggest that this may lead to the release of MCC components from APC/C. BubR1 in MCC is ubiquitylated by APC/C, although to a lesser degree than Cdc20. The extent of BubR1 ubiquitylation was markedly increased in recombinant MCC that contained a lysine-less mutant of Cdc20. Mutation of lysine residues to arginines in the N-terminal region of BubR1 partially inhibited its ubiquitylation and slowed down the release of MCC from APC/C, provided that Cdc20 ubiquitylation was also blocked. It is suggested that ubiquitylation of both Cdc20 and BubR1 may be involved in their dissociation from each other and in the release of MCC components from APC/C.

scholarly journals Global phosphoproteomics reveals DYRK1A regulates CDK1 activity in glioblastoma cells

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Ariadna Recasens ◽  
Sean J. Humphrey ◽  
Michael Ellis ◽  
Monira Hoque ◽  
Ramzi H. Abbassi ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Cyclin B ◽  
Anaphase Promoting Complex ◽  
Mechanistic Studies ◽  
Glioblastoma Cells ◽  
Cycle Arrest ◽  
Dual Specificity ◽  
Rb Pathway ◽  
High Doses

AbstractBoth tumour suppressive and oncogenic functions have been reported for dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A). Herein, we performed a detailed investigation to delineate the role of DYRK1A in glioblastoma. Our phosphoproteomic and mechanistic studies show that DYRK1A induces degradation of cyclin B by phosphorylating CDC23, which is necessary for the function of the anaphase-promoting complex, a ubiquitin ligase that degrades mitotic proteins. DYRK1A inhibition leads to the accumulation of cyclin B and activation of CDK1. Importantly, we established that the phenotypic response of glioblastoma cells to DYRK1A inhibition depends on both retinoblastoma (RB) expression and the degree of residual DYRK1A activity. Moderate DYRK1A inhibition leads to moderate cyclin B accumulation, CDK1 activation and increased proliferation in RB-deficient cells. In RB-proficient cells, cyclin B/CDK1 activation in response to DYRK1A inhibition is neutralized by the RB pathway, resulting in an unchanged proliferation rate. In contrast, complete DYRK1A inhibition with high doses of inhibitors results in massive cyclin B accumulation, saturation of CDK1 activity and cell cycle arrest, regardless of RB status. These findings provide new insights into the complexity of context-dependent DYRK1A signalling in cancer cells.

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.

Activation mechanisms of the E3 ubiquitin ligase parkin

2017 ◽  
Vol 474 (18) ◽  
pp. 3075-3086 ◽  
Author(s):  
Nikhil Panicker ◽  
Valina L. Dawson ◽  
Ted M. Dawson
Keyword(s):  
Parkinson’S Disease ◽  
Amino Acid ◽  
Ubiquitin Ligase ◽  
Recent Literature ◽  
E3 Ubiquitin Ligase ◽  
Mitochondrial Damage ◽  
Cytosolic Protein ◽  
Mitochondrial Functions ◽  
Activation Mechanisms

Monogenetic, familial forms of Parkinson's disease (PD) only account for 5–10% of the total number of PD cases, but analysis of the genes involved therein is invaluable to understanding PD-associated neurodegenerative signaling. One such gene, parkin, encodes a 465 amino acid E3 ubiquitin ligase. Of late, there has been considerable interest in the role of parkin signaling in PD and in identifying its putative substrates, as well as the elucidation of the mechanisms through which parkin itself is activated. Its dysfunction underlies both inherited and idiopathic PD-associated neurodegeneration. Here, we review recent literature that provides a model of activation of parkin in the setting of mitochondrial damage that involves PINK1 (PTEN-induced kinase-1) and phosphoubiquitin. We note that neuronal parkin is primarily a cytosolic protein (with various non-mitochondrial functions), and discuss potential cytosolic parkin activation mechanisms.

scholarly journals Loss of Cdc20 Causes a Securin-Dependent Metaphase Arrest in Two-Cell Mouse Embryos

2007 ◽  
Vol 27 (9) ◽  
pp. 3481-3488 ◽  
Author(s):  
Min Li ◽  
J. Philippe York ◽  
Pumin Zhang
Keyword(s):  
Ubiquitin Ligase ◽  
Cyclin B1 ◽  
Mitotic Exit ◽  
Adapter Proteins ◽  
Anaphase Promoting Complex ◽  
Metaphase Arrest ◽  
Cell Stage ◽  
Gene Trapping ◽  
Protein Substrates

ABSTRACT The anaphase-promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase mediating targeted proteolysis through ubiquitination of protein substrates to control the progression of mitosis. The APC/C recognizes its substrates through two adapter proteins, Cdc20 and Cdh1, which contain similar C-terminal domains composed of seven WD-40 repeats believed to be involved in interacting with their substrates. During the transition from metaphase to anaphase, APC/C-Cdc20 mediates the ubiquitination of securin and cyclin B1, allowing the activation of separase and the onset of anaphase and mitotic exit. APC/C-Cdc20 and APC/C-Cdh1 have overlapping substrates. It is unclear whether they are redundant for mitosis. Using a gene-trapping approach, we have obtained mice which lack Cdc20 function. These mice show failed embryogenesis. The embryos were arrested in metaphase at the two-cell stage with high levels of cyclin B1, indicating an essential role of Cdc20 in mitosis that is not redundant with that of Cdh1. Interestingly, Cdc20 and securin double mutant embryos could not maintain the metaphase arrest, suggesting a role of securin in preventing mitotic exit.

Vps13D functions in a Pink1-dependent and Parkin-independent mitophagy pathway

2021 ◽  
Vol 220 (11) ◽  
Author(s):  
James L. Shen ◽  
Tina M. Fortier ◽  
Ruoxi Wang ◽  
Eric H. Baehrecke
Keyword(s):  
Neurodegenerative Diseases ◽  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Mitochondrial Morphology ◽  
The Core ◽  
Mitochondrial Defects ◽  
Mutant Cells

Defects in autophagy cause problems in metabolism, development, and disease. The autophagic clearance of mitochondria, mitophagy, is impaired by the loss of Vps13D. Here, we discover that Vps13D regulates mitophagy in a pathway that depends on the core autophagy machinery by regulating Atg8a and ubiquitin localization. This process is Pink1 dependent, with loss of pink1 having similar autophagy and mitochondrial defects as loss of vps13d. The role of Pink1 has largely been studied in tandem with Park/Parkin, an E3 ubiquitin ligase that is widely considered to be crucial in Pink1-dependent mitophagy. Surprisingly, we find that loss of park does not exhibit the same autophagy and mitochondrial deficiencies as vps13d and pink1 mutant cells and contributes to mitochondrial clearance through a pathway that is parallel to vps13d. These findings provide a Park-independent pathway for Pink1-regulated mitophagy and help to explain how Vps13D regulates autophagy and mitochondrial morphology and contributes to neurodegenerative diseases.

scholarly journals Role of the E3 Ubiquitin Ligase TRIM4 in Predicting the Prognosis of Hepatocellular Carcinoma

2020 ◽  
Vol 11 (14) ◽  
pp. 4007-4014
Author(s):  
Zhao-Ru Dong ◽  
Wei Zhou ◽  
Dong Sun ◽  
Yu-Chuan Yan ◽  
Chun-Cheng Yang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase

scholarly journals Deubiquitinating enzyme USP30 maintains basal peroxisome abundance by regulating pexophagy

2019 ◽  
Vol 218 (3) ◽  
pp. 798-807 ◽  
Author(s):  
Victoria Riccio ◽  
Nicholas Demers ◽  
Rong Hua ◽  
Miluska Vissa ◽  
Derrick T. Cheng ◽  
...  
Keyword(s):  
Amino Acid ◽  
Ubiquitin Ligase ◽  
Cell Function ◽  
E3 Ubiquitin Ligase ◽  
Metabolic Stress ◽  
Amino Acid Starvation ◽  
Deubiquitinating Enzyme ◽  
Potential Therapeutic Target ◽  
Autophagic Degradation

The regulation of organelle abundance is critical for cell function and survival; however, the mechanisms responsible are not fully understood. In this study, we characterize a role of the deubiquitinating enzyme USP30 in peroxisome maintenance. Peroxisomes are highly dynamic, changing in abundance in response to metabolic stress. In our recent study identifying the role of USP30 in mitophagy, we observed USP30 to be localized to punctate structures resembling peroxisomes. We report here that USP30, best known as a mitophagy regulator, is also necessary for regulating pexophagy, the selective autophagic degradation of peroxisomes. We find that overexpressing USP30 prevents pexophagy during amino acid starvation, and its depletion results in pexophagy induction under basal conditions. We demonstrate that USP30 prevents pexophagy by counteracting the action of the peroxisomal E3 ubiquitin ligase PEX2. Finally, we show that USP30 can rescue the peroxisome loss observed in some disease-causing peroxisome mutations, pointing to a potential therapeutic target.

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