scholarly journals Intricate Regulatory Mechanisms of the Anaphase-Promoting Complex/Cyclosome and Its Role in Chromatin Regulation

2021 ◽  
Vol 9 ◽  
Author(s):  
Tatyana Bodrug ◽  
Kaeli A. Welsh ◽  
Megan Hinkle ◽  
Michael J. Emanuele ◽  
Nicholas G. Brown
Keyword(s):  
Cell Cycle ◽  
Signaling Pathways ◽  
Biological Process ◽  
Conformational Dynamics ◽  
Intimate Relationship ◽  
Regulatory Mechanisms ◽  
Cell Cycle Regulators ◽  
Chromatin Regulation ◽  
Anaphase Promoting Complex

The ubiquitin (Ub)-proteasome system is vital to nearly every biological process in eukaryotes. Specifically, the conjugation of Ub to target proteins by Ub ligases, such as the Anaphase-Promoting Complex/Cyclosome (APC/C), is paramount for cell cycle transitions as it leads to the irreversible destruction of cell cycle regulators by the proteasome. Through this activity, the RING Ub ligase APC/C governs mitosis, G1, and numerous aspects of neurobiology. Pioneering cryo-EM, biochemical reconstitution, and cell-based studies have illuminated many aspects of the conformational dynamics of this large, multi-subunit complex and the sophisticated regulation of APC/C function. More recent studies have revealed new mechanisms that selectively dictate APC/C activity and explore additional pathways that are controlled by APC/C-mediated ubiquitination, including an intimate relationship with chromatin regulation. These tasks go beyond the traditional cell cycle role historically ascribed to the APC/C. Here, we review these novel findings, examine the mechanistic implications of APC/C regulation, and discuss the role of the APC/C in previously unappreciated signaling pathways.

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.

scholarly journals The possible role of cell cycle regulators in multistep process of HPV-associated cervical carcinoma

2007 ◽  
Vol 7 (1) ◽  
Author(s):  
Abeer A Bahnassy ◽  
Abdel Rahman N Zekri ◽  
Maha Saleh ◽  
Mohammad Lotayef ◽  
Manar Moneir ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cervical Carcinoma ◽  
Cell Cycle Regulators ◽  
Multistep Process

scholarly journals Regulation of Cell Cycle Progression by Growth Factor-Induced Cell Signaling

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3327
Author(s):  
Zhixiang Wang
Keyword(s):  
Cell Cycle ◽  
Growth Factor ◽  
Signaling Pathways ◽  
Tyrosine Kinases ◽  
Cell Cycle Progression ◽  
Phase Cell ◽  
Growth Factor Signaling ◽  
Cycle Progression ◽  
M Phase

The cell cycle is the series of events that take place in a cell, which drives it to divide and produce two new daughter cells. The typical cell cycle in eukaryotes is composed of the following phases: G1, S, G2, and M phase. Cell cycle progression is mediated by cyclin-dependent kinases (Cdks) and their regulatory cyclin subunits. However, the driving force of cell cycle progression is growth factor-initiated signaling pathways that control the activity of various Cdk–cyclin complexes. While the mechanism underlying the role of growth factor signaling in G1 phase of cell cycle progression has been largely revealed due to early extensive research, little is known regarding the function and mechanism of growth factor signaling in regulating other phases of the cell cycle, including S, G2, and M phase. In this review, we briefly discuss the process of cell cycle progression through various phases, and we focus on the role of signaling pathways activated by growth factors and their receptor (mostly receptor tyrosine kinases) in regulating cell cycle progression through various phases.

scholarly journals APC/C: current understanding and future perspectives

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 725 ◽  
Author(s):  
Hiroyuki Yamano
Keyword(s):  
Cell Cycle ◽  
Molecular Mechanisms ◽  
Current Understanding ◽  
Historical Background ◽  
Cell Cycle Regulators ◽  
Anaphase Promoting Complex ◽  
Electron Microscopy Analysis ◽  
Cellular Machinery ◽  
The Many ◽  
Ubiquitin Conjugating Enzymes

The separation of sister chromatids at anaphase, which is regulated by an E3 ubiquitin ligase called the anaphase-promoting complex/cyclosome (APC/C), is arguably the most important irrevocable event during the cell cycle. The APC/C and cyclin-dependent kinase 1 (Cdk1) are just two of the many significant cell cycle regulators and exert control through ubiquitylation and phosphorylation, respectively. The temporal and spatial regulation of the APC/C is achieved by multiple mechanisms, including phosphorylation, interaction with the structurally related co-activators Cdc20 and Cdh1, loading of distinct E2 ubiquitin-conjugating enzymes, binding with inhibitors and differential affinities for various substrates. Since the discovery of APC/C 25 years ago, intensive studies have uncovered many aspects of APC/C regulation, but we are still far from a full understanding of this important cellular machinery. Recent high-resolution cryogenic electron microscopy analysis and reconstitution of the APC/C have greatly advanced our understanding of molecular mechanisms underpinning the enzymatic properties of APC/C. In this review, we will examine the historical background and current understanding of APC/C regulation.

scholarly journals The role of SCF ubiquitin-ligase complex at the beginning of life

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Jiayan Xie ◽  
Yimei Jin ◽  
Guang Wang
Keyword(s):  
Cell Cycle ◽  
Ubiquitin Ligase ◽  
Cellular Proteins ◽  
Cell Cycle Regulators ◽  
Signal Transducers ◽  
E3 Ligases ◽  
Cellular Processes ◽  
Ubiquitin Ligase Complex ◽  
Scf Ubiquitin Ligase

AbstractAs the largest family of E3 ligases, the Skp1-cullin 1-F-box (SCF) E3 ligase complex is comprised of Cullins, Skp1 and F-box proteins. And the SCF E3 ubiquitin ligases play an important role in regulating critical cellular processes, which promote degradation of many cellular proteins, including signal transducers, cell cycle regulators, and transcription factors. We review the biological roles of the SCF ubiquitin-ligase complex in gametogenesis, oocyte-to-embryo transition, embryo development and the regulation for estrogen and progestin. We find that researches about the SCF ubiquitin-ligase complex at the beginning of life are not comprehensive, thus more in-depth researches will promote its eventual clinical application.

CELL CYCLE: The Expanding Role of Cell Cycle Regulators

Science ◽  
1998 ◽  
Vol 280 (5366) ◽  
pp. 1035-1036 ◽  
Author(s):  
T. Jacks
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Regulators

scholarly journals γ-Tubulin plays a key role in inactivating APC/CCdh1 at the G1–S boundary

2012 ◽  
Vol 198 (5) ◽  
pp. 785-791 ◽  
Author(s):  
Heather Edgerton-Morgan ◽  
Berl R. Oakley
Keyword(s):  
Cell Cycle ◽  
Spindle Pole Body ◽  
Spindle Pole ◽  
Cyclin B ◽  
Anaphase Promoting Complex ◽  
Gene Encoding ◽  
Localization Pattern ◽  
Pole Body ◽  
Dependent Inactivation

A γ-tubulin mutation in Aspergillus nidulans, mipA-D159, causes failure of inactivation of the anaphase-promoting complex/cyclosome (APC/C) in interphase, resulting in failure of cyclin B (CB) accumulation and removal of nuclei from the cell cycle. We have investigated the role of CdhA, the A. nidulans homologue of the APC/C activator protein Cdh1, in γ-tubulin–dependent inactivation of the APC/C. CdhA was not essential, but it targeted CB for destruction in G1, and APC/CCdhA had to be inactivated for the G1–S transition. mipA-D159 altered the localization pattern of CdhA, and deletion of the gene encoding CdhA allowed CB to accumulate in all nuclei in strains carrying mipA-D159. These data indicate that mipA-D159 causes a failure of inactivation of APC/CCdhA at G1–S, perhaps by altering its localization to the spindle pole body, and, thus, that γ-tubulin plays an important role in inactivating APC/CCdhA at this point in the cell cycle.

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