scholarly journals Selective dephosphorylation by PP2A-B55 directs the meiosis I - meiosis II transition in oocytes

2020 ◽  
Author(s):  
S. Zachary Swartz ◽  
Hieu T. Nguyen ◽  
Brennan C. McEwan ◽  
Mark E. Adamo ◽  
Iain M. Cheeseman ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Time Course ◽  
Phosphorylation Site ◽  
Sea Star ◽  
Meiotic Stage ◽  
Protein Levels ◽  
Substrate Preferences ◽  
Embryonic Cleavage ◽  
Meiosis I

AbstractMeiosis is a specialized cell cycle that requires sequential changes to the cell division machinery to facilitate changing functions. To define the mechanisms that enable the oocyte-to-embryo transition, we performed time-course proteomics in sea star oocytes from prophase I through the first embryonic cleavage. Although protein levels are broadly stable, dynamic waves of phosphorylation underlie each meiotic stage. We find that the phosphatase PP2A-B55 is reactivated at the Meiosis I/II transition resulting in the preferential dephosphorylation of threonine residues. Selective dephosphorylation is critical for directing the MI / MII transition as altering PP2A-B55 substrate preferences disrupts key cell cycle events after meiosis I. In addition, threonine to serine substitution of a conserved phosphorylation site in the substrate INCENP prevents its relocalization at anaphase I. Thus, through its inherent phospho-threonine preference, PP2A-B55 rewires the cell division apparatus to direct the MI / MII transition.

scholarly journals Selective dephosphorylation by PP2A-B55 directs the meiosis I - meiosis II transition in oocytes

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
S Zachary Swartz ◽  
Hieu T Nguyen ◽  
Brennan C McEwan ◽  
Mark E Adamo ◽  
Iain M Cheeseman ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Time Course ◽  
Phosphorylation Site ◽  
Sea Star ◽  
Meiotic Stage ◽  
Protein Levels ◽  
Substrate Preferences ◽  
Embryonic Cleavage ◽  
Meiosis I

Meiosis is a specialized cell cycle that requires sequential changes to the cell division machinery to facilitate changing functions. To define the mechanisms that enable the oocyte-to-embryo transition, we performed time-course proteomics in synchronized sea star oocytes from prophase I through the first embryonic cleavage. Although we find that protein levels are broadly stable, our analysis reveals that dynamic waves of phosphorylation underlie each meiotic stage. We find that the phosphatase PP2A-B55 is reactivated at the meiosis I/II transition resulting in the preferential dephosphorylation of threonine residues. Selective dephosphorylation is critical for directing the MI / MII transition as altering PP2A-B55 substrate preferences disrupts key cell cycle events after meiosis I. In addition, threonine to serine substitution of a conserved phosphorylation site in the substrate INCENP prevents its relocalization at anaphase I. Thus, through its inherent phospho-threonine preference, PP2A-B55 imposes specific phosphoregulated behaviors that distinguish the two meiotic divisions.

Protein kinase cascades in meiotic and mitotic cell cycle control

1990 ◽  
Vol 68 (12) ◽  
pp. 1297-1330 ◽  
Author(s):  
Steven L. Pelech ◽  
Jasbinder S. Sanghera ◽  
Maleki Daya-Makin
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Protein Kinase ◽  
Tyrosine Kinases ◽  
Somatic Cells ◽  
Protein Tyrosine Kinases ◽  
Sea Star ◽  
Protein Tyrosine ◽  
Threonine Kinases ◽  
Cell Division Control

Eukaryotic cell cycle progression during meiosis and mitosis is extensively regulated by reversible protein phosphorylation. Many cell surface receptors for mitogens are ligand-stimulated protein-tyrosine kinases that control the activation of a network of cytoplasmic and nuclear protein-serine(threonine) kinases. Over 30 plasma membrane associated protein-tyrosine kinases are encoded by proto-oncogenes, i.e., genes that have the potential to facilitate cancer when disregulated. Proteins such as ribosomal protein S6, microtubule-associated protein-2, myelin basic protein, and casein have been used to detect intracellular protein-serine(threonine) kinases that are activated further downstream in growth factor signalling transduction cascades. Genetic analysis of yeast cell division control (cdc) mutants has revealed another 20 or so protein-serine(threonine) kinases. One of these, specified by the cdc-2 gene in Schizosaccharomyces pombe, has homologs that are stimulated during M phase in maturing sea star and frog oocytes and mammalian somatic cells. Furthermore, during meiotic maturation in these echinoderm and amphibian oocytes, this is followed by activation of many of the same protein-serine(threonine) kinases that are stimulated when quiescent mammalian somatic cells are prompted with mitogens to traverse from G0 to G1 phase. These findings imply that a similar protein kinase cascade may oversee progression at multiple points in the cell cycle.Key words: protein kinases, mitosis, meiosis, oncogenes, cell division control.

scholarly journals Effects of cell-cycle-dependent expression on random fluctuations in protein levels

2016 ◽  
Vol 3 (12) ◽  
pp. 160578 ◽  
Author(s):  
Mohammad Soltani ◽  
Abhyudai Singh
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Protein Levels ◽  
Stochastic Component ◽  
Stochastic Expression ◽  
A Cell ◽  
Intrinsic Stochasticity ◽  
Cycle Dependent ◽  
Random Fluctuations ◽  
Cell To Cell Variability

Expression of many genes varies as a cell transitions through different cell-cycle stages. How coupling between stochastic expression and cell cycle impacts cell-to-cell variability (noise) in the level of protein is not well understood. We analyse a model where a stable protein is synthesized in random bursts, and the frequency with which bursts occur varies within the cell cycle. Formulae quantifying the extent of fluctuations in the protein copy number are derived and decomposed into components arising from the cell cycle and stochastic processes. The latter stochastic component represents contributions from bursty expression and errors incurred during partitioning of molecules between daughter cells. These formulae reveal an interesting trade-off: cell-cycle dependencies that amplify the noise contribution from bursty expression also attenuate the contribution from partitioning errors. We investigate the existence of optimum strategies for coupling expression to the cell cycle that minimize the stochastic component. Intriguingly, results show that a zero production rate throughout the cell cycle, with expression only occurring just before cell division, minimizes noise from bursty expression for a fixed mean protein level. By contrast, the optimal strategy in the case of partitioning errors is to make the protein just after cell division. We provide examples of regulatory proteins that are expressed only towards the end of the cell cycle, and argue that such strategies enhance robustness of cell-cycle decisions to the intrinsic stochasticity of gene expression.

scholarly journals Whi5 and Stb1 define redundant pathways through which the G1 cyclin Cln3 promotes cell division

2021 ◽  
Author(s):  
Sangeet Honey ◽  
Bruce Futcher
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Transcription Factors ◽  
Cell Division ◽  
Transcriptional Repression ◽  
Phosphorylation Site ◽  
Phosphorylation Sites ◽  
G1 Cyclin ◽  
Cdk Phosphorylation ◽  
Commitment To Cell Division

In the budding yeast S. cerevisiae, commitment to cell division, Start, is promoted by a trio of G1 cyclins, Cln1, Cln2, and Cln3, that activate the CDK kinase Cdc28. The active kinases somehow activate two transcription factors, SBF and MBF, leading to induction of about 100 genes for budding, DNA synthesis, and other early cell cycle processes. Activation of the transcription factors is opposed by a repressive protein called Whi5, and also by a second repressive protein called Stb1. Both Whi5 and Stb1 contain many potential sites for phosphorylation by CDK kinase, and is thought that relief of transcriptional repression involves the phosphorylation of Whi5 and Stb1 by CDK. Phosphorylation site mutants have been studied for Whi5, but not for Stb1. Here, we create phosphorylation site mutants of Stb1, and combine them with site mutants of Whi5. We find that the G1 cyclin Cln3 activates cell cycle transcription effectively when at least one of these proteins has its phosphorylation sites. However, when both Whi5 and Stb1 simultaneously lack all consensus phosphorylation sites, Cln3 is unable, or almost unable, to induce any gene expression, or any advancement of Start. Thus the G1 cyclin signaling pathway to Start has a requirement for CDK phosphorylation sites on either Whi5 or Stb1.

Cell Division

2019 ◽  
pp. 93-114
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Chromosome Number ◽  
Sexual Reproduction ◽  
Germ Cells ◽  
Growth And Development ◽  
Reduction Division ◽  
Regulatory Proteins ◽  
Chromosomal Number ◽  
Meiosis I

Cells divide for three main reasons: growth and development, replace worn-out or injured cells, and reproduction of offspring. Cell division is part of the cell cycle divided into five distinct phases. The diploid state of the cell is the normal chromosomal number in species. During sexual reproduction, the cell's chromosome number is reduced to a haploid state to ensure constancy in chromosome number and thus continuation of the species. The process of cell division is controlled by regulatory proteins. Mitosis occurs in all body cells and is divided into four phases. Meiosis, which occurs in only the germ cells involved in reproduction, divides the chromosomes in two rounds termed meiosis I and meiosis II (reduction division). The human lifecycle starts with gametogenesis, the process that forms gametes which then combine to form a zygote. The zygote quickly becomes an embryo and develops rapidly into a foetus. This chapter explores cell division.

Cyclin B mRNA depletion only transiently inhibits the Xenopus embryonic cell cycle

Development ◽  
1991 ◽  
Vol 111 (4) ◽  
pp. 1173-1178 ◽  
Author(s):  
D.L. Weeks ◽  
J.A. Walder ◽  
J.M. Dagle
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Antisense Oligonucleotides ◽  
Normal Development ◽  
Embryonic Cell ◽  
Cyclin B ◽  
Xenopus Embryos ◽  
Embryonic Cleavage ◽  
Embryonic Cell Cycle

The control of the cell cycle is dependent on the ability to synthesize and degrade proteins called cyclins. When antisense oligonucleotides are used to deplete Xenopus embryos of mRNA encoding cyclin B protein, embryonic cleavage is inhibited. Surprisingly, after missing several rounds of cleavage, the cell cycle and cell division resumes. These studies indicate that the early embryonic cell cycle can proceed with undetectable levels of cyclin B encoding mRNA. In contrast, other events of normal development, including the activation of embryonic transcription and gastrulation, are inhibited.

Periodic sensitivity of mechanisms of cytodifferentiation in cleaving eggs of Limnaea stagnalis

Development ◽  
1964 ◽  
Vol 12 (2) ◽  
pp. 183-195
Author(s):  
W. L. M. Geilenkirchen
Keyword(s):  
Cell Cycle ◽  
Protein Synthesis ◽  
Cell Division ◽  
Dna Replication ◽  
Time Course ◽  
Chromosome Doubling ◽  
Daughter Cells ◽  
Morphogenetic Factors ◽  
Limnaea Stagnalis

Investigations on cellular reproduction have led to a highly resolved and integrated picture of the cell cycle in a morphological and physiological sense. The various preparations for division, doubling of components or syntheses, follow their own time course parallel to one another. It has become evident that the various factors involved in cell division are dissociable, for example chromosome doubling and reproduction of centrioles (Bucher & Mazia, 1960), DNA replication and protein synthesis (Zeuthen, 1961). The conditions for cell division in general are applicable to division of egg cells. However, in addition in egg cells there is a complicating system of morphogenetic factors acting, as must be postulated from the observation that in ‘mosaic’ eggs the fate of the blastomeres is fixed. In dividing eggs differences between daughter cells may be due to local differences established during oögenesis in the mother which are parcelled out during cleavages.

scholarly journals Control of the mitotic exit network during meiosis

2012 ◽  
Vol 23 (16) ◽  
pp. 3122-3132 ◽  
Author(s):  
Michelle A. Attner ◽  
Angelika Amon
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Signaling Pathway ◽  
Vegetative Growth ◽  
Spindle Pole ◽  
Mitotic Exit ◽  
Regulatory Pathways ◽  
Spindle Pole Bodies ◽  
Mitotic Exit Network ◽  
Meiosis I

The mitotic exit network (MEN) is an essential GTPase signaling pathway that triggers exit from mitosis in budding yeast. We show here that during meiosis, the MEN is dispensable for exit from meiosis I but contributes to the timely exit from meiosis II. Consistent with a role for the MEN during meiosis II, we find that the signaling pathway is active only during meiosis II. Our analysis further shows that MEN signaling is modulated during meiosis in several key ways. Whereas binding of MEN components to spindle pole bodies (SPBs) is necessary for MEN signaling during mitosis, during meiosis MEN signaling occurs off SPBs and does not require the SPB recruitment factor Nud1. Furthermore, unlike during mitosis, MEN signaling is controlled through the regulated interaction between the MEN kinase Dbf20 and its activating subunit Mob1. Our data lead to the conclusion that a pathway essential for vegetative growth is largely dispensable for the specialized meiotic divisions and provide insights into how cell cycle regulatory pathways are modulated to accommodate different modes of cell division.

scholarly journals The Transcriptional Repressor HBP1 Is a Target of the p38 Mitogen-Activated Protein Kinase Pathway in Cell Cycle Regulation

2003 ◽  
Vol 23 (23) ◽  
pp. 8890-8901 ◽  
Author(s):  
Mei Xiu ◽  
Jiyoung Kim ◽  
Ellen Sampson ◽  
Chun-Yin Huang ◽  
Roger J. Davis ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Map Kinase ◽  
Transcriptional Repression ◽  
Cell Cycle Regulation ◽  
Phosphorylation Site ◽  
P38 Map Kinase ◽  
Protein Levels ◽  
Mitogen Activated Protein ◽  
Protein Instability ◽  
Cycle Regulation

ABSTRACT The p38 mitogen-activated protein (MAP) kinase signaling pathway participates in both apoptosis and G1 arrest. In contrast to the established role in apoptosis, the documented induction of G1 arrest by activation of the p38 MAP kinase pathway has attracted recent attention with reports of substrates that are linked to cell cycle regulation. Here, we identify the high-mobility group box protein HBP1 transcriptional repressor as a new substrate for p38 MAP kinase. Our previous work had shown that HBP1 inhibits G1 progression in cell and animal models, and thus indicated that HBP1 could be a relevant substrate for p38 MAP kinase in cell cycle regulation. In the present work, a p38 MAP kinase docking site (amino acids [aa] 81 to 125) and a p38 MAP kinase phosphorylation site (serine 401) were identified in the HBP1 protein. Furthermore, the docking and phosphorylation sites on HBP1 were specific for p38 MAP kinase. In defining the role of p38 MAP kinase regulation, the inhibition of p38 MAP kinase activity was shown to decrease HBP1 protein levels by triggering protein instability, as manifested by a decrease in protein half-life. Consistently, a decrease in protein levels was accompanied by a decrease in overall DNA binding activity. A mutation of the p38 MAP kinase phosphorylation site at aa 401 [(S-A)401HBP1] also triggered HBP1 protein instability. While protein stability was compromised by mutation, the specific activities of (S-A)401HBP1 and of wild-type HBP1 appeared comparable for transcriptional repression. This comparison of transcription-specific activity highlighted that p38 MAP kinase regulated HBP1 protein levels but not the intrinsic activity for DNA binding or for transcriptional repression. Finally, p38 MAP kinase-mediated regulation of the HBP1 protein also contributed to the regulation of G1 progression. Together, our work supports a molecular framework in which p38 MAP kinase activity contributes to cell cycle inhibition by increasing HBP1 and other G1 inhibitory factors by regulating protein stability.

scholarly journals Abundances of transcripts, proteins, and metabolites in the cell cycle of budding yeast reveals coordinate control of lipid metabolism

2019 ◽  
Author(s):  
Heidi M. Blank ◽  
Ophelia Papoulas ◽  
Nairita Maitra ◽  
Riddhiman Garge ◽  
Brian K. Kennedy ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Lipid Metabolism ◽  
Cell Division ◽  
Ribosome Biogenesis ◽  
Budding Yeast ◽  
Eukaryotic Cell ◽  
Yeast Cells ◽  
Protein Levels ◽  
Coordinate Control ◽  
Cycle Dependent

ABSTRACTEstablishing the pattern of abundance of molecules of interest during cell division has been a long-standing goal of cell cycle studies. In several systems, including the budding yeast Saccharomyces cerevisiae, cell cycle-dependent changes in the transcriptome are well studied. In contrast, few studies queried the proteome during cell division, and they are often plagued by low agreement with each other and with previous transcriptomic datasets. There is also little information about dynamic changes in the levels of metabolites and lipids in the cell cycle. Here, for the first time in any system, we present experiment-matched datasets of the levels of RNAs, proteins, metabolites, and lipids from un-arrested, growing, and synchronously dividing yeast cells. Overall, transcript and protein levels were correlated, but specific processes that appeared to change at the RNA level (e.g., ribosome biogenesis), did not do so at the protein level, and vice versa. We also found no significant changes in codon usage or the ribosome content during the cell cycle. We describe an unexpected mitotic peak in the abundance of ergosterol and thiamine biosynthesis enzymes. Although the levels of several metabolites changed in the cell cycle, by far the most significant changes were in the lipid repertoire, with phospholipids and triglycerides peaking strongly late in the cell cycle. Our findings provide an integrated view of the abundance of biomolecules in the eukaryotic cell cycle and point to a coordinate mitotic control of lipid metabolism.

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