scholarly journals Reversible cytoplasmic localization of the proteasome in quiescent yeast cells

2008 ◽  
Vol 181 (5) ◽  
pp. 737-745 ◽  
Author(s):  
Damien Laporte ◽  
Bénédicte Salin ◽  
Bertrand Daignan-Fornier ◽  
Isabelle Sagot
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
26S Proteasome ◽  
Yeast Cells ◽  
Cell Cycle Regulators ◽  
Cycle Progression ◽  
Vast Number ◽  
Proteasome Subunits ◽  
Storage Granules ◽  
Cytoplasmic Structures

The 26S proteasome is responsible for the controlled proteolysis of a vast number of proteins, including crucial cell cycle regulators. Accordingly, in Saccharomyces cerevisiae, 26S proteasome function is mandatory for cell cycle progression. In budding yeast, the 26S proteasome is assembled in the nucleus, where it is localized throughout the cell cycle. We report that upon cell entry into quiescence, proteasome subunits massively relocalize from the nucleus into motile cytoplasmic structures. We further demonstrate that these structures are proteasome cytoplasmic reservoirs that are rapidly mobilized upon exit from quiescence. Therefore, we have named these previously unknown structures proteasome storage granules (PSGs). Finally, we observe conserved formation and mobilization of these PSGs in the evolutionary distant yeast Schizosaccharomyces pombe. This conservation implies a broad significance for these proteasome reserves.

scholarly journals Compartmentalized nodes control mitotic entry signaling in fission yeast

2013 ◽  
Vol 24 (12) ◽  
pp. 1872-1881 ◽  
Author(s):  
Lin Deng ◽  
James B. Moseley
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Fission Yeast ◽  
Cell Polarity ◽  
Cell Cycle Progression ◽  
Interaction Network ◽  
Yeast Cells ◽  
Cell Cortex ◽  
Cycle Progression ◽  
Mitotic Entry

Cell cycle progression is coupled to cell growth, but the mechanisms that generate growth-dependent cell cycle progression remain unclear. Fission yeast cells enter into mitosis at a defined size due to the conserved cell cycle kinases Cdr1 and Cdr2, which localize to a set of cortical nodes in the cell middle. Cdr2 is regulated by the cell polarity kinase Pom1, suggesting that interactions between cell polarity proteins and the Cdr1-Cdr2 module might underlie the coordination of cell growth and division. To identify the molecular connections between Cdr1/2 and cell polarity, we performed a comprehensive pairwise yeast two-hybrid screen. From the resulting interaction network, we found that the protein Skb1 interacted with both Cdr1 and the Cdr1 inhibitory target Wee1. Skb1 inhibited mitotic entry through negative regulation of Cdr1 and localized to both the cytoplasm and a novel set of cortical nodes. Skb1 nodes were distinct structures from Cdr1/2 nodes, and artificial targeting of Skb1 to Cdr1/2 nodes delayed entry into mitosis. We propose that the formation of distinct node structures in the cell cortex controls signaling pathways to link cell growth and division.

scholarly journals JAK/STAT pathway promotes Drosophila neuroblast proliferation via the direct CycE regulation

2020 ◽  
Author(s):  
Lijuan Du ◽  
Jian Wang
Keyword(s):  
Cell Cycle ◽  
Signaling Pathway ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Control Cell ◽  
Proliferative Potential ◽  
Cell Cycle Regulators ◽  
Cycle Progression ◽  
Stat Signaling ◽  
Stat Pathway

AbstractHow neural stem cells regulate their proliferative potential and lineage diversity is a central problem in developmental neurobiology. Drosophila Mushroom bodies (MBs), centers of olfactory learning and memory, are generated by a specific set of neuroblasts (Nbs) that are born in the embryonic stage and continuously proliferate till the end of the pupal stage. Although MB presents an excellent model for studying neural stem cell proliferation, the genetic and molecular mechanisms that control the unique proliferative characteristics of the MB Nbs are largely unknown. Further, the signaling cues controlling cell cycle regulators to promote cell cycle progression in MB Nbs remain poorly understood. Here, we report that JAK/STAT signaling pathway is required for the proliferation activity and maintenance of MB Nbs. Loss of JAK/STAT activity severely reduces the later-born MB neuron types and leads to premature neuroblast termination, which can be rescued by tissue-specific overexpression of CycE and diap1. Higher JAK/STAT pathway activity in MB results in more neurons, without producing supernumerary Nbs. Furthermore, we show that JAK/STAT signaling effector Stat92E directly regulates CycE transcription in MB Nbs. Finally, MB Nb clones of loss or excess CycE phenocopy those of decreased or increased JAK/STAT signaling pathway activities. We conclude that JAK/STAT signaling controls MB Nb proliferative activity through directly regulating CycE expression to control cell cycle progression.

The MEIS1 Interactome in Megakaryocytes Reveals a Role in Cell Cycle Regulation,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3380-3380
Author(s):  
Vishal A Salunkhe ◽  
Iain Macaulay ◽  
Sylvia Nuernberg ◽  
Cathal McCarthy ◽  
Willem Hendrik Ouwehand ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Regulation ◽  
Cell Cycle Progression ◽  
Cyclin D3 ◽  
Haematopoietic Stem Cell ◽  
Nuclear Fraction ◽  
Cell Cycle Regulators ◽  
Cycle Progression ◽  
Cycle Regulation

Abstract Abstract 3380 Haematopoiesis is highly coordinated process of fate determination at branch points that is regulated by transcription factors and their cofactors. Our comprehensive catalogue of transcripts in the eight main mature blood cell elements, including erythroblasts and megakaryocytes (MKs) showed that the transcription factor MEIS1 is uniquely transcribed in MKs and the CD34+ haematopoietic stem cell. Gene silencing studies in mice and zebrafish has shown a pivotal role for MEIS1 in haematopoiesis, megakaryopoiesis and vasculogenesis, although its precise hierarchical position and function remain unknown. To gain further insight in the role of MEIS1 in megakaryopoiesis, we used a proteomics approach to search for its nuclear interaction partners. Co-immunoprecipitation was used to isolate MEIS1 interacting proteins from the nuclear fraction of the MK cell line, CHRF 288–11 and resulting eluates were subjected to proteomics analysis using one-dimensional electrophoresis and liquid chromatography (LC) coupled to tandem mass spectrometry (MS) or GeLC-MS/MS. In total 70 proteins were identified to co-immunoprecipitate with MEIS1 from 3 replicate MS analyses. These included the previously validated MEIS1 interactors PBX1 and HOXB9, as well as numerous novel interactors such as ARID3B and DHX9. Network analysis of our MEIS1 interactome dataset revealed a strong association with cell cycle regulation. In fact, we had identified a myriad of cell cycle regulators including CDK1, CDK2, CDK9, CUL3, PCNA, CDC5L, ARID3B and MDC1. These interactions are consistent with recent microarray studies in promyelocytic leukemic cell lines that link MEIS1 with cell cycle entry and its regulation of genes such as CDK2, CDK6, CDKN3, CDC7 and Cyclin D3 among others. To confirm the novel interaction of MK MEIS1 with cell cycle regulators we performed reverse immuno-precipitation/immunoblot analysis in CHRF cells and purified MEIS1 containing multiprotein complexes from L8057 murine megakaryoblastic cells. Using a cell cycle specific PCR array, we demonstrate that MEIS1 overexpression in L8057 cells regulates numerous cell cycle regulatory genes. Preliminary analysis using flow cytometry demonstrated that MEIS1 overexpression resulted in an altered cell cycle progression. Furthermore, genome wide ChIP-Seq analysis in CHRF cells for MEIS1 revealed binding sites in Cyclin D3 and CDK6, two known key regulators of the cell cycle and megakaryopoiesis. Taken together this study provides evidence linking MEIS1 to the cell cycle control of MKs and will help elucidate the role of MEIS1 in cell cycle progression, megakaryopoiesis and associated disorders. Disclosures: No relevant conflicts of interest to declare.

A putative dual-specific protein phosphatase encoded by YVH1 controls growth, filamentation and virulence in Candida albicans

Microbiology ◽  
2005 ◽  
Vol 151 (7) ◽  
pp. 2223-2232 ◽  
Author(s):  
Nozomu Hanaoka ◽  
Takashi Umeyama ◽  
Keigo Ueno ◽  
Kenji Ueda ◽  
Teruhiko Beppu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Candida Albicans ◽  
Cell Cycle Progression ◽  
Germ Tube ◽  
Hyphal Growth ◽  
Tube Formation ◽  
Yeast Cells ◽  
Nucleotide Polymorphisms ◽  
Wild Type ◽  
Cycle Progression

In response to stimulants, such as serum, the yeast cells of the opportunistic fungal pathogen Candida albicans form germ tubes, which develop into hyphae. Yvh1p, one of the 29 protein phosphatases encoded in the C. albicans genome, has 45 % identity with the dual-specific phosphatase Yvh1p of the model yeast Saccharomyces cerevisiae. In this study, Yvh1p expression was not observed during the initial step of germ tube formation, although Yvh1p was expressed constitutively in cell cycle progression of yeast or hyphal cells. In an attempt to analyse the function of Yvh1p phosphatase, the complete ORFs of both alleles were deleted by replacement with hph200–URA3–hph200 and ARG4. Although YVH1 has nine single-nucleotide polymorphisms in its coding sequence, both YVH1 alleles were able to complement the YVH1 gene disruptant. The vegetative growth of Δyvh1 was significantly slower than the wild-type. The hyphal growth of Δyvh1 on agar, or in a liquid medium, was also slower than the wild-type because of the delay in nuclear division and septum formation, although germ tube formation was similar between the wild-type and the disruptant. Despite the slow hyphal growth, the expression of several hypha-specific genes in Δyvh1 was not delayed or repressed compared with that of the wild-type. Infection studies using mouse models revealed that the virulence of Δyvh1 was less than that of the wild-type. Thus, YVH1 contributes to normal vegetative yeast or hyphal cell cycle progression and pathogenicity, but not to germ tube formation.

Proteasomes are a target of the anti-tumour drug vinblastine

2001 ◽  
Vol 356 (3) ◽  
pp. 835-841 ◽  
Author(s):  
Marco PICCININI ◽  
Ornella TAZARTES ◽  
Caterina MEZZATESTA ◽  
Emanuela RICOTTI ◽  
Stefano BEDINO ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Proteasome Inhibitors ◽  
Drug Dose ◽  
26S Proteasome ◽  
Cell Physiology ◽  
Cycle Progression ◽  
Hl60 Cells ◽  
Block Cell Cycle Progression

Proteasomes, the proteolytic machinery of the ubiquitin/ATP-dependent pathway, have a relevant role in many processes crucial for cell physiology and cell cycle progression. Proteasome inhibitors are used to block cell cycle progression and to induce apoptosis in certain cell lines. Here we examine whether proteasomal function is affected by the anti-tumour drug vinblastine, whose cytostatic action relies mainly on the disruption of mitotic spindle dynamics. The effects of vinblastine on the peptidase activities of human 20S and 26S proteasomes and on the proteolytic activity of 26S proteasome were assessed in the presence of specific fluorogenic peptides and 125I-lysozyme–ubiquitin conjugates respectively. The assays of ubiquitin–protein conjugates and of inhibitory κBα (IκBα), which are characteristic intracellular proteasome substrates, by Western blotting on lysates from HL60 cells incubated with or without vinblastine, illustrated the effects of vinblastine on proteasomes in vivo. We also evaluated the effects of vinblastine on the signal-induced degradation of IκBα. Vinblastine at 3–110μM reversibly inhibited the chymotrypsin-like activity of the 20 S proteasome and the trypsin-like and peptidyl-glutamyl-peptide hydrolysing activities of both proteasomes, but only at 110μM vinblastine was the chymotrypsin-like activity of the 26S proteasome inhibited; furthermore, at 25–200μM the drug inhibited the degradation of ubiquitinated lysozyme. In HL60 cells exposed for 6h to 0.5–10μM vinblastine, the drug-dose-related accumulation of polyubiquitinated proteins, as well as that of a high-molecular-mass form of IκBα, occurred. Moreover, vinblastine impaired the signal-induced degradation of IκBα. Cell viability throughout the test was approx. 95%. Proteasomes can be considered to be a new and additional vinblastine target.

Cyclin A2: a genuine cell cycle regulator?

2012 ◽  
Vol 3 (6) ◽  
pp. 535-543 ◽  
Author(s):  
Nawal Bendris ◽  
Abdelhalim Loukil ◽  
Caroline Cheung ◽  
Nikola Arsic ◽  
Cosette Rebouissou ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Posttranslational Modifications ◽  
Cell Cycle Progression ◽  
Current Knowledge ◽  
Cell Cycle Regulators ◽  
Cycle Progression ◽  
Cell Cycle Regulator ◽  
Its Gene ◽  
Cyclin A2 ◽  
Shed Light

AbstractCyclin A2 belongs to the core cell cycle regulators and participates in the control of both S phase and mitosis. However, several observations suggest that it is also endowed with other functions, and our recent data shed light on its involvement in cytoskeleton dynamic and cell motility. From the transcription of its gene to its posttranslational modifications, cyclin A2 regulation reveals the complexity of the regulatory network shaping cell cycle progression. We summarize our current knowledge on this cell cycle regulator and discuss recent findings raising the possibility that cyclin A2 might play a much broader role in epithelial tissues homeostasis.

scholarly journals Dynamic NF-κB and E2F interactions control the priority and timing of inflammatory signalling and cell proliferation

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
John M Ankers ◽  
Raheela Awais ◽  
Nicholas A Jones ◽  
James Boyd ◽  
Sheila Ryan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cellular Response ◽  
Cell Cycle Progression ◽  
Nuclear Factor Kappa B ◽  
Cellular Systems ◽  
Cell Cycle Regulators ◽  
Cycle Progression ◽  
Response To Stress ◽  
Computational Analyses ◽  
Inflammatory Signalling

Dynamic cellular systems reprogram gene expression to ensure appropriate cellular fate responses to specific extracellular cues. Here we demonstrate that the dynamics of Nuclear Factor kappa B (NF-κB) signalling and the cell cycle are prioritised differently depending on the timing of an inflammatory signal. Using iterative experimental and computational analyses, we show physical and functional interactions between NF-κB and the E2 Factor 1 (E2F-1) and E2 Factor 4 (E2F-4) cell cycle regulators. These interactions modulate the NF-κB response. In S-phase, the NF-κB response was delayed or repressed, while cell cycle progression was unimpeded. By contrast, activation of NF-κB at the G1/S boundary resulted in a longer cell cycle and more synchronous initial NF-κB responses between cells. These data identify new mechanisms by which the cellular response to stress is differentially controlled at different stages of the cell cycle.

scholarly journals Human CPR (Cell Cycle Progression Restoration) Genes Impart a Far– Phenotype on Yeast Cells

Genetics ◽  
1997 ◽  
Vol 147 (3) ◽  
pp. 1063-1076 ◽  
Author(s):  
Michael C Edwards ◽  
Nanette Liegeois ◽  
Joe Horecka ◽  
Ronald A DePinho ◽  
George F Sprague ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Growth Control ◽  
Yeast Cells ◽  
G1 Arrest ◽  
Mating Pheromone ◽  
Cycle Progression ◽  
Yeast Genes

Regulated cell cycle progression depends on the proper integration of growth control pathways with the basic cell cycle machinery. While many of the central molecules such as cyclins, CDKs, and CKIs are known, and many of the kinases and phosphatases that modify the CDKs have been identified, little is known about the additional layers of regulation that impinge upon these molecules. To identify new regulators of cell proliferation, we have selected for human and yeast cDNAs that when overexpressed were capable of specifically overcoming G1 arrest signals from the cell cycle branch of the mating pheromone pathway, while still maintaining the integrity of the transcriptional induction branch. We have identified 13 human CPR (cell cycle progression restoration) genes and 11 yeast OPY (overproduction-induced pheromone-resistant yeast) genes that specifically block the G1 arrest by mating pheromone. The CPR genes represent a variety of biochemical functions including a new cyclin, a tumor suppressor binding protein, chaperones, transcription factors, translation factors, RNA-binding proteins, as well as novel proteins. Several CPR genes require individual CLNs to promote pheromone resistance and those that require CLN3 increase the basal levels of Cln3 protein. Moreover, several of the yeast OPY genes have overlapping functions with the human CPR genes, indicating a possible conservation of roles.

scholarly journals Multiple inputs ensure yeast cell size homeostasis during cell cycle progression

2017 ◽  
Author(s):  
Cecilia Garmendia-Torres ◽  
Olivier Tassy ◽  
Audrey Matifas ◽  
Nacho Molina ◽  
Gilles Charvin
Keyword(s):  
Cell Cycle ◽  
Cell Size ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Size Control ◽  
Large Cell ◽  
Yeast Cells ◽  
Cycle Progression ◽  
Size Variability

AbstractCoordination of cell growth and division is essential for proper cell function. In budding yeast, although some molecular mechanisms responsible for cell size control during G1 have been elucidated, the mechanism by which cell size homeostasis is established and maintained throughout the cell cycle remains to be discovered. Here, we developed a new technique based on quantification of histone levels to monitor cell cycle progression in individual yeast cells with unprecedented accuracy. Our analysis establishes the existence of a strong mechanism controlling bud size in G2/M that prevents premature entry into mitosis, and contributes significantly to the overall control of size variability during the cell cycle. While most G1/S regulation mutants do not display any strongly impaired size homeostasis, mutants in which B-type cyclin regulation is altered display large cell-to-cell size variability. Our study thus demonstrates that size homeostasis is not controlled by a G1-specific mechanism but is likely to be an emergent property resulting from the integration of several mechanisms, including the control of cyclin B-Cdk activity, that coordinate cell and bud growth with division.

A mutation in the yeast heat-shock factor gene causes temperature-sensitive defects in both mitochondrial protein import and the cell cycle

1991 ◽  
Vol 11 (5) ◽  
pp. 2647-2655 ◽  
Author(s):  
B J Smith ◽  
M P Yaffe
Keyword(s):  
Cell Cycle ◽  
Heat Shock ◽  
Cell Cycle Progression ◽  
Protein Import ◽  
Mitochondrial Protein ◽  
Yeast Cells ◽  
Heat Shock Gene ◽  
Temperature Sensitive ◽  
Mitochondrial Protein Import ◽  
Cycle Progression

Yeast cells containing the recessive mas3 mutation display temperature-sensitive defects in both mitochondrial protein import and the cell division cycle. The import defect is characterized by two pools of mitochondrial precursors and a dramatically slower rate of posttranslational import. The effect of mas3 on cell cycle progression occurs within one cell cycle at the nonpermissive temperature and retards progression through the G2 stage. The mas3 mutation maps to the gene encoding yeast heat-shock transcription factor (HSF), and expression of wild-type HSF complements the temperature-sensitive defects. The mas3 lesion has no apparent effect on protein secretion. In mas3 cells, induction of a major heat-shock gene, SSA1, is defective at 37 degrees C. The properties of the mas3 mutant cells indicate that HSF mediates the response to stress of two basic cellular processes: mitochondrial protein import and cell cycle progression.

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