scholarly journals Ribosomal Protein uL11 as a Regulator of Metabolic Circuits Related to Aging and Cell Cycle

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1745
Author(s):  
Mateusz Mołoń ◽  
Eliza Molestak ◽  
Monika Kula-Maximenko ◽  
Przemysław Grela ◽  
Marek Tchórzewski
Keyword(s):  
Cell Cycle ◽  
Ribosomal Protein ◽  
Protein Biosynthesis ◽  
Integrated Approach ◽  
Sole Source ◽  
Energy Restriction ◽  
Living Organisms ◽  
Translational Apparatus ◽  
Yeast Mutants ◽  
Mutant Cells

Aging is a biological phenomenon common to all living organisms. It is thought that the rate of aging is influenced by diverse factors, in many cases related to the control of energy metabolism, i.e., the so-called pro-longevity effects of starvation. Translation, regarded as the main energy consumption process, lies at the center of interest, as it has a significant impact on the longevity phenomenon. It has been shown that perturbations in the translational apparatus may lead to a lower rate of aging. Therefore, the main aim of this study was to investigate aging in relation to the protein biosynthesis circuit, taking into account the uL11 ribosomal protein as a vital ribosomal element. To this end, we used set of yeast mutants with deleted single uL11A or uL11B genes and a double disruptant uL11AB mutant. We applied an integrated approach analyzing a broad range of biological parameters of yeast mutant cells, especially the longevity phenomenon, supplemented with biochemical and high throughput transcriptomic and metobolomic approaches. The analysis showed that the longevity phenomenon is not fully related to the commonly considered energy restriction effect, thus the slow-down of translation does not represent the sole source of aging. Additionally, we showed that uL11 can be classified as a moonlighting protein with extra-ribosomal function having cell-cycle regulatory potential.

scholarly journals The HBx protein of hepatitis B virus regulates the expression, intracellular distribution and functions of ribosomal protein S27a

2012 ◽  
Vol 93 (4) ◽  
pp. 706-715 ◽  
Author(s):  
Grace Fatima ◽  
Ganeshan Mathan ◽  
Vijay Kumar
Keyword(s):  
Cell Cycle ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Ribosomal Protein ◽  
Cell Cycle Progression ◽  
Protein Biosynthesis ◽  
Intracellular Distribution ◽  
Cdna Subtraction ◽  
Remarkable Change ◽  
B Virus

The pleiotropic HBx protein of hepatitis B virus is linked functionally to the development of hepatocellular carcinoma (HCC) via effectors and signalling pathways of the host. To identify such effectors in a macrocarcinogenic environment, a PCR-based cDNA subtraction analysis was carried out in the X15-myc oncomouse model of HCC. Altogether, 19 categories of genes, mainly involved in protein biosynthesis and the electron-transport chain, were found to be upregulated in the liver of these mice. Ribosomal protein S27a (RPS27a), which is a natural fusion protein of N-terminal ubiquitin and C-terminal extension protein (CEP), topped the list of expressed genes, with >20-fold higher expression compared with its normal level. Sustained and elevated expression of RPS27a in the mouse liver and its moderate expression in cell culture in the presence of HBx suggested an indirect role of RPS27a in hepatocarcinogenesis. Nevertheless, a remarkable change in the intracellular distribution of ubiquitin from cytoplasm to late-endosomal lysosomes, and of CEP from nucleoli to the perinucleolar region/nuclear foci, was observed in the presence of HBx. RPS27a accelerated the progression of the cell cycle and cooperated with HBx in this process. Further, the knockdown of RPS27a expression by RNA interference in an HBx microenvironment led to retarded cell-cycle progression and reduced cell size. Thus, these results suggest strongly that RPS27a could be an effector of HBx-mediated hepatocarcinogenesis.

Yeast dom34 Mutants Are Defective in Multiple Developmental Pathways and Exhibit Decreased Levels of Polyribosomes

Genetics ◽  
1998 ◽  
Vol 149 (1) ◽  
pp. 45-56
Author(s):  
Luther Davis ◽  
JoAnne Engebrecht
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Heterologous Expression ◽  
Protein Translation ◽  
Developmental Pathways ◽  
G1 Phase ◽  
Growth Defect ◽  
Wild Type ◽  
Drosophila Homolog ◽  
Mutant Cells

Abstract The DOM34 gene of Saccharomyces cerevisiae is similar togenes found in diverse eukaryotes and archaebacteria. Analysis of dom34 strains shows that progression through the G1 phase of the cell cycle is delayed, mutant cells enter meiosis aberrantly, and their ability to form pseudohyphae is significantly diminished. RPS30A, which encodes ribosomal protein S30, was identified in a screen for high-copy suppressors of the dom34Δ growth defect. dom34Δ mutants display an altered polyribosome profile that is rescued by expression of RPS30A. Taken together, these data indicate that Dom34p functions in protein translation to promote G1 progression and differentiation. A Drosophila homolog of Dom34p, pelota, is required for the proper coordination of meiosis and spermatogenesis. Heterologous expression of pelota in dom34Δ mutants restores wild-type growth and differentiation, suggesting conservation of function between the eukaryotic members of the gene family.

scholarly journals DDRE-03. IDH1-MUTANT GBM CELLS ARE HIGHLY SENSITIVE TO COMBINATION OF KDM6A/B AND HDAC INHIBITORS

2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. i6-i7
Author(s):  
Alişan Kayabölen ◽  
Gizem Nur Sahin ◽  
Fidan Seker ◽  
Ahmet Cingöz ◽  
Bekir Isik ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Mutant Cell ◽  
Glioma Cells ◽  
Epigenetic Therapy ◽  
Low Grade ◽  
Orthotopic Model ◽  
Cycle Arrest ◽  
Mutant Cells

Abstract Mutations in IDH1 and IDH2 genes are common in low grade gliomas and secondary GBM and are known to cause a distinct epigenetic landscape in these tumors. To interrogate the epigenetic vulnerabilities of IDH-mutant gliomas, we performed a chemical screen with inhibitors of chromatin modifiers and identified 5-azacytidine, Chaetocin, GSK-J4 and Belinostat as potent agents against primary IDH1-mutant cell lines. Testing the combinatorial efficacy of these agents, we demonstrated GSK-J4 and Belinostat combination as a very effective treatment for the IDH1-mutant glioma cells. Engineering established cell lines to ectopically express IDH1R132H, we showed that IDH1R132H cells adopted a different transcriptome with changes in stress-related pathways that were reversible with the mutant IDH1 inhibitor, GSK864. The combination of GSK-J4 and Belinostat was highly effective on IDH1R132H cells, but not on wt glioma cells or nonmalignant fibroblasts and astrocytes. The cell death induced by GSK-J4 and Belinostat combination involved the induction of cell cycle arrest and apoptosis. RNA sequencing analyses revealed activation of inflammatory and unfolded protein response pathways in IDH1-mutant cells upon treatment with GSK-J4 and Belinostat conferring increased stress to glioma cells. Specifically, GSK-J4 induced ATF4-mediated integrated stress response and Belinostat induced cell cycle arrest in primary IDH1-mutant glioma cells; which were accompanied by DDIT3/CHOP-dependent upregulation of apoptosis. Moreover, to dissect out the responsible target histone demethylase, we undertook genetic approach and demonstrated that CRISPR/Cas9 mediated ablation of both KDM6A and KDM6B genes phenocopied the effects of GSK-J4 in IDH1-mutant cells. Finally, GSK-J4 and Belinostat combination significantly decreased tumor growth and increased survival in an orthotopic model in mice. Together, these results suggest a potential combination epigenetic therapy against IDH1-mutant gliomas.

scholarly journals Far3 and Five Interacting Proteins Prevent Premature Recovery from Pheromone Arrest in the Budding Yeast Saccharomyces cerevisiae

2003 ◽  
Vol 23 (5) ◽  
pp. 1750-1763 ◽  
Author(s):  
Hilary A. Kemp ◽  
George F. Sprague,
Keyword(s):  
Cell Cycle ◽  
Budding Yeast ◽  
Open Reading Frames ◽  
Velocity Sedimentation ◽  
Interacting Proteins ◽  
Yeast Saccharomyces Cerevisiae ◽  
Cycle Arrest ◽  
Mutant Cells ◽  
Two Hybrid ◽  
Reading Frames

ABSTRACT In budding yeast, diffusible mating pheromones initiate a signaling pathway that culminates in several responses, including cell cycle arrest. Only a handful of genes required for the interface between pheromone response and the cell cycle have been identified, among them FAR1 and FAR3; of these, only FAR1 has been extensively characterized. In an effort to learn about the mechanism by which Far3 acts, we used the two-hybrid method to identify interacting proteins. We identified five previously uncharacterized open reading frames, dubbed FAR7, FAR8, FAR9, FAR10, and FAR11, that cause a far3-like pheromone arrest defect when disrupted. Using two-hybrid and coimmunoprecipitation analysis, we found that all six Far proteins interact with each other. Moreover, velocity sedimentation experiments suggest that Far3 and Far7 to Far11 form a complex. The phenotype of a sextuple far3far7-far11 mutant is no more severe than any single mutant. Thus, FAR3 and FAR7 to FAR11 all participate in the same pathway leading to G1 arrest. These mutants initially arrest in response to pheromone but resume budding after 10 h. Under these conditions, wild-type cells fail to resume budding even after several days whereas far1 mutant cells resume budding within 1 h. We conclude that the FAR3-dependent arrest pathway is functionally distinct from that which employs FAR1.

Identification of spatial specifically expressed genes in rice (Oryza sativa) seedlings using cDNA microarray

2004 ◽  
Vol 1 (2) ◽  
pp. 133-139
Author(s):  
Sun Liang-Xian ◽  
Dong Hai-Tao ◽  
Zhuang Xiao-Feng ◽  
Zhang Feng ◽  
Li De-Bao
Keyword(s):  
Ribosomal Protein ◽  
Lipid Transfer Protein ◽  
Protein Biosynthesis ◽  
Critical Role ◽  
Phosphoglycerate Kinase ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Metabolic Reaction ◽  
Lipid Transfer ◽  
Molecular Physiology

AbstractMembranous cDNA microarrays containing 2200 unique rice transcripts were designed for screening the characteristics of spatially expressed genes in post-germination rice seedlings. By comparing the profiles obtained, 31 genes were identified as expressed specifically in the plumule, 36 in the mesocotyl and 73 in the radicle. Several genes, such as polyubiquitin, UDP-glucose pyrophosphorylase, sucrose synthase and phosphoglycerate kinase, which encode components of the carbohydrate or protein metabolic reaction cascades, were expressed specifically in the mesocotyl, indicating that degradation reactions of the endospermous reserve starch and proteins occur mainly in the mesocotyl during the post-germination stage. A number of genes involved in defence mechanisms or in the processes of replication, transcription and translation were identified as expressed specifically in the plumule or radicle. Among plumule specifically expressed genes, translation initiation factor 5a, 40s ribosomal protein s28 and ribosomal protein 136 are considered to have a critical role in protein biosynthesis; while allergenic protein, β-D-glucan exohydrolase and actin 11 are genes with defending functions. Among the catalogue of radicle specifically expressed genes, EF-1a, Tat binding protein, replication protein A2, histone h3.2, ribosomal protein s29a and 40s ribosomal protein s19 are genes that function in the process of replication, transcription or translation; whereas glycine-rich protein, wound-induced basic protein, Bowman-Birk proteinase inhibitor and lipid transfer protein-2 are genes involved in defence responses. Results of this experiment have provided insight into post-germination molecular physiology at the genomic level of gene expression.

scholarly journals Ribosomal Protein S6 Gene Haploinsufficiency Is Associated with Activation of a p53-Dependent Checkpoint during Gastrulation

2006 ◽  
Vol 26 (23) ◽  
pp. 8880-8891 ◽  
Author(s):  
Linda Panić ◽  
Sanda Tamarut ◽  
Melanie Sticker-Jantscheff ◽  
Martina Barkić ◽  
Davor Solter ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Embryonic Development ◽  
Ribosomal Protein ◽  
Ribosome Biogenesis ◽  
Fetal Liver ◽  
Genetic Inactivation ◽  
Developmental Program ◽  
Ribosomal Protein S6 ◽  
M Phase ◽  
Insight Into

ABSTRACT Nascent ribosome biogenesis is required during cell growth. To gain insight into the importance of this process during mouse oogenesis and embryonic development, we deleted one allele of the ribosomal protein S6 gene in growing oocytes and generated S6-heterozygous embryos. Oogenesis and embryonic development until embryonic day 5.5 (E5.5) were normal. However, inhibition of entry into M phase of the cell cycle and apoptosis became evident post-E5.5 and led to perigastrulation lethality. Genetic inactivation of p53 bypassed this checkpoint and prolonged development until E12.5, when the embryos died, showing decreased expression of D-type cyclins, diminished fetal liver erythropoiesis, and placental defects. Thus, a p53-dependent checkpoint is activated during gastrulation in response to ribosome insufficiency to prevent improper execution of the developmental program.

Mild temperature shock alters the transcription of a discrete class of Saccharomyces cerevisiae genes

1983 ◽  
Vol 3 (3) ◽  
pp. 457-465
Author(s):  
C H Kim ◽  
J R Warner
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Ribosomal Protein ◽  
Ribosomal Proteins ◽  
Temperature Shift ◽  
Restrictive Temperature ◽  
Ribosomal Protein Genes ◽  
Wild Type ◽  
Temperature Shock ◽  
Mild Temperature ◽  
Mutant Cells

In Saccharomyces cerevisiae the synthesis of ribosomal proteins declines temporarily after a culture has been subjected to a mild temperature shock, i.e., a shift from 23 to 36 degrees C, each of which support growth. Using cloned genes for several S. cerevisiae ribosomal proteins, we found that the changes in the synthesis of ribosomal proteins parallel the changes in the concentration of mRNA of each. The disappearance and reappearance of the mRNA is due to a brief but severe inhibition of the transcription of each of the ribosomal protein genes, although the total transcription of mRNA in the cells is relatively unaffected by the temperature shock. The precisely coordinated response of these genes, which are scattered throughout the genome, suggests that either they or the enzyme which transcribes them has unique properties. In certain S. cerevisiae mutants, the synthesis of ribosomal proteins never recovers from a temperature shift. Yet both the decline and the resumption of transcription of these genes during the 30 min after the temperature shift are indistinguishable from those in wild-type cells. The failure of the mutant cells to grow at the restrictive temperature appears to be due to their inability to process the RNA transcribed from genes which have introns (Rosbash et al., Cell 24:679-686, 1981), a large proportion of which appear to be ribosomal protein genes.

scholarly journals dE2F2-Independent Rescue of Proliferation in Cells Lacking an Activator dE2F1

2007 ◽  
Vol 27 (24) ◽  
pp. 8561-8570 ◽  
Author(s):  
Aaron M. Ambrus ◽  
Brandon N. Nicolay ◽  
Vanya I. Rasheva ◽  
Richard J. Suckling ◽  
Maxim V. Frolov
Keyword(s):  
Cell Cycle ◽  
Morphogenetic Furrow ◽  
Independent Manner ◽  
Dead Box ◽  
Cycle Arrest ◽  
Eye Disc ◽  
Severe Reduction ◽  
Functional Inactivation ◽  
Mutant Cells ◽  
Dependent Mechanism

ABSTRACT In Drosophila melanogaster, the loss of activator de2f1 leads to a severe reduction in cell proliferation and repression of E2F targets. To date, the only known way to rescue the proliferation block in de2f1 mutants was through the inactivation of dE2F2. This suggests that dE2F2 provides a major contribution to the de2f1 mutant phenotype. Here, we report that in mosaic animals, in addition to de2f2, the loss of a DEAD box protein Belle (Bel) also rescues proliferation of de2f1 mutant cells. Surprisingly, the rescue occurs in a dE2F2-independent manner since the loss of Bel does not relieve dE2F2-mediated repression. In the eye disc, bel mutant cells fail to undergo a G1 arrest in the morphogenetic furrow, delay photoreceptor recruitment and differentiation, and show a reduction of the transcription factor Ci155. The down-regulation of Ci155 is important since it is sufficient to partially rescue proliferation of de2f1 mutant cells. Thus, mutation of bel relieves the dE2F2-mediated cell cycle arrest in de2f1 mutant cells through a novel Ci155-dependent mechanism without functional inactivation of the dE2F2 repressor.

scholarly journals COMPLEX ASSESSMENT OF BIOSOLID FOR AGRICULTURE USING LIVING ORGANISMS UNDER LABORATORY CONDITIONS

AGROFOR ◽  
2020 ◽  
Vol 5 (3) ◽  
Author(s):  
Ksenia PONOGAYBO ◽  
Liudmila VORONINA
Keyword(s):  
Tetrahymena Pyriformis ◽  
Integrated Approach ◽  
Water Soluble ◽  
Municipal Sewage ◽  
Municipal Sewage Sludge ◽  
Soil Extraction ◽  
Luminescent Bacteria ◽  
Wide Range ◽  
Test Organisms ◽  
Living Organisms

The use of biosolids (treated municipal sewage sludge) as a fertilizer is the best way of their disposal. However, not all of them are suitable for use as a fertilizer. Biosolids should be subject to mandatory laboratory control to confirm their safety. Two directions of research on biosolids are being improved: chemical and biological. Chemical analysis methods allow us to determine the qualitative composition of complex waste. The biological approach (use of living organisms) allows us to estimate the total toxicity of all the components. Accordingly, a distinctive characteristic of biological methods is the integrated approach. We examined biosolid extract using a wide range of bioassay methods. As test organisms, we took Daphnia magna Straus, Paramecium caudatum Ehrenberg, Tetrahymena pyriformis, luminescent bacteria Escherichia coli. In addition, a phytotest was carried out on the culture of Avena sativa L. and Raphanus sativus L. None of the tests revealed a high toxicity of biosolid. Biosolid safety was confirmed by a low content of potentially toxic water-soluble elements – (μg /l): Al3+ – 980; Ba2+ – 19; B – 140; Mn – 360; Cu – 61; As – 57; Ni – 200; Pb – 1,4; Sr2+ – 302; Cr – 18; Zn2+ – 310; Co – 30; Mo – 56; (mg/l): Na+ – 16,8; Fe – 1,0. The bioassay methods make it possible to give an indicative safety assessment of this type of object by the effect of readily soluble (readily available) components from this object on living organisms and plants. The use of bioassay methods using soil extraction as a control tool allows to take into account the combined effect of the presence in the extraction of not only toxic elements that suppress the vital activity of organisms, but also of elements that attract and stimulate the activity of test-organisms.

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