scholarly journals YBP1 and Its Homologue YBP2/YBH1 Influence Oxidative-Stress Tolerance by Nonidentical Mechanisms in Saccharomyces cerevisiae

2004 ◽  
Vol 3 (2) ◽  
pp. 318-330 ◽  
Author(s):  
Kailash Gulshan ◽  
Sherry A. Rovinsky ◽  
W. Scott Moye-Rowley
Keyword(s):  
Oxidative Stress ◽  
Saccharomyces Cerevisiae ◽  
Transcription Factor ◽  
Protein Interactions ◽  
Nuclear Accumulation ◽  
Protein Protein Interactions ◽  
Homologous Proteins ◽  
Oxidative Stresses ◽  
Double Mutant Strain ◽  
Biochemical Analyses

ABSTRACT In the yeast Saccharomyces cerevisiae, the transcription factor Yap1p is a central determinant of resistance to oxidative stress. Previous work has demonstrated that Yap1p is recruited from the cytoplasm to the nucleus upon exposure to the oxidants diamide and H2O2 in a process that requires the transient covalent linkage of the glutathione peroxidase Gpx3p to Yap1p. Genetic and biochemical analyses indicate that while both oxidants trigger nuclear accumulation of Yap1p, the function and regulation of this transcription factor is different under these two different oxidative stresses. Ybp1p (Yap1p-binding protein) has recently been demonstrated to be required for Yap1p-mediated H2O2 resistance but not diamide resistance. A Ybp1p homologous protein (Ybh1p/Ybp2p) was also detected in the S. cerevisiae genome. Here we compare the actions of these two closely related proteins and provide evidence that while both factors influence H2O2 tolerance, they do so by nonidentical mechanisms. A double mutant strain lacking both YBP1 and YBH1 genes is more sensitive to H2O2 and more defective in activation of Yap1p-dependent gene expression than either single mutant. Ybp1p has a more pronounced effect on these phenotypes than does Ybh1p. Protein-protein interactions between Yap1p and Ybp1p could be detected by either the yeast two-hybrid or coimmunoprecipitation approach while neither technique could demonstrate Yap1p-Ybh1p interactions. Overexpression experiments indicated that high levels of Ybh1p but not Ybp1p could bypass the H2O2 hypersensitivity of a gpx3Δ strain. Together, these data argue that these two homologous proteins act as parallel positive regulators of H2O2 tolerance.

GRR1 of Saccharomyces cerevisiae is required for glucose repression and encodes a protein with leucine-rich repeats

1991 ◽  
Vol 11 (10) ◽  
pp. 5101-5112
Author(s):  
J S Flick ◽  
M Johnston
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Protein Interactions ◽  
Tandem Repeats ◽  
Glucose Repression ◽  
Molecular Data ◽  
Primary Response ◽  
Yeast Cells ◽  
Cell Fractionation ◽  
Protein Protein Interactions ◽  
Yeast Saccharomyces Cerevisiae

Growth of the yeast Saccharomyces cerevisiae on glucose leads to repression of transcription of many genes required for alternative carbohydrate metabolism. The GRR1 gene appears to be of central importance to the glucose repression mechanism, because mutations in GRR1 result in a pleiotropic loss of glucose repression (R. Bailey and A. Woodword, Mol. Gen. Genet. 193:507-512, 1984). We have isolated the GRR1 gene and determined that null mutants are viable and display a number of growth defects in addition to the loss of glucose repression. Surprisingly, grr1 mutations convert SUC2, normally a glucose-repressed gene, into a glucose-induced gene. GRR1 encodes a protein of 1,151 amino acids that is expressed constitutively at low levels in yeast cells. GRR1 protein contains 12 tandem repeats of a sequence similar to leucine-rich motifs found in other proteins that may mediate protein-protein interactions. Indeed, cell fractionation studies are consistent with this view, suggesting that GRR1 protein is tightly associated with a particulate protein fraction in yeast extracts. The combined genetic and molecular data are consistent with the idea that GRR1 protein is a primary response element in the glucose repression pathway and is required for the generation or interpretation of the signal that induces glucose repression.

scholarly journals Glycyrrhizic Acid for COVID-19: Findings of Targeting Pivotal Inflammatory Pathways Triggered by SARS-CoV-2

2021 ◽  
Vol 12 ◽  
Author(s):  
Wenjiang Zheng ◽  
Xiufang Huang ◽  
Yanni Lai ◽  
Xiaohong Liu ◽  
Yong Jiang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Protein Interactions ◽  
Glycyrrhizic Acid ◽  
Enrichment Analysis ◽  
Host Factors ◽  
Pathway Enrichment Analysis ◽  
Protein Protein Interactions ◽  
Health Crisis ◽  
Inflammatory Pathways ◽  
Anti Inflammatory

Background: Coronavirus disease 2019 (COVID-19) is now a worldwide public health crisis. The causative pathogen is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Novel therapeutic agents are desperately needed. Because of the frequent mutations in the virus and its ability to cause cytokine storms, targeting the viral proteins has some drawbacks. Targeting cellular factors or pivotal inflammatory pathways triggered by SARS-CoV-2 may produce a broader range of therapies. Glycyrrhizic acid (GA) might be beneficial against SARS-CoV-2 because of its anti-inflammatory and antiviral characteristics and possible ability to regulate crucial host factors. However, the mechanism underlying how GA regulates host factors remains to be determined.Methods: In our report, we conducted a bioinformatics analysis to identify possible GA targets, biological functions, protein-protein interactions, transcription-factor-gene interactions, transcription-factor-miRNA coregulatory networks, and the signaling pathways of GA against COVID-19.Results: Protein-protein interactions and network analysis showed that ICAM1, MMP9, TLR2, and SOCS3 had higher degree values, which may be key targets of GA for COVID-19. GO analysis indicated that the response to reactive oxygen species was significantly enriched. Pathway enrichment analysis showed that the IL-17, IL-6, TNF-α, IFN signals, complement system, and growth factor receptor signaling are the main pathways. The interactions of TF genes and miRNA with common targets and the activity of TFs were also recognized.Conclusions: GA may inhibit COVID-19 through its anti-oxidant, anti-viral, and anti-inflammatory effects, and its ability to activate the immune system, and targeted therapy for those pathways is a predominant strategy to inhibit the cytokine storms triggered by SARS-CoV-2 infection.

Carnoquinolines Target Copper Dyshomeostasis, Aberrant Protein–Protein Interactions, and Oxidative Stress

2020 ◽  
Vol 26 (70) ◽  
pp. 16690-16705
Author(s):  
Francesco Bellia ◽  
Giuseppa Ida Grasso ◽  
Ikhlas Mohamed Mohamud Ahmed ◽  
Valentina Oliveri ◽  
Graziella Vecchio
Keyword(s):  
Oxidative Stress ◽  
Protein Interactions ◽  
Protein Protein Interactions ◽  
Aberrant Protein ◽  
Copper Dyshomeostasis ◽  
And Oxidative Stress

scholarly journals Saccharomyces cerevisiae as a Tool to Investigate Plant Potassium and Sodium Transporters

2019 ◽  
Vol 20 (9) ◽  
pp. 2133 ◽  
Author(s):  
Antonella Locascio ◽  
Nuria Andrés-Colás ◽  
José Miguel Mulet ◽  
Lynne Yenush
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Protein Interactions ◽  
Model System ◽  
Protein Protein Interactions ◽  
Alkali Cations ◽  
Yeast Saccharomyces Cerevisiae ◽  
Future Directions ◽  
Sodium Transporters ◽  
Adverse Environmental Conditions ◽  
Sodium And Potassium

Sodium and potassium are two alkali cations abundant in the biosphere. Potassium is essential for plants and its concentration must be maintained at approximately 150 mM in the plant cell cytoplasm including under circumstances where its concentration is much lower in soil. On the other hand, sodium must be extruded from the plant or accumulated either in the vacuole or in specific plant structures. Maintaining a high intracellular K+/Na+ ratio under adverse environmental conditions or in the presence of salt is essential to maintain cellular homeostasis and to avoid toxicity. The baker’s yeast, Saccharomyces cerevisiae, has been used to identify and characterize participants in potassium and sodium homeostasis in plants for many years. Its utility resides in the fact that the electric gradient across the membrane and the vacuoles is similar to plants. Most plant proteins can be expressed in yeast and are functional in this unicellular model system, which allows for productive structure-function studies for ion transporting proteins. Moreover, yeast can also be used as a high-throughput platform for the identification of genes that confer stress tolerance and for the study of protein–protein interactions. In this review, we summarize advances regarding potassium and sodium transport that have been discovered using the yeast model system, the state-of-the-art of the available techniques and the future directions and opportunities in this field.

scholarly journals Molecular strategies to increase yeast iron accumulation and resistance

Metallomics ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1245-1256 ◽  
Author(s):  
Lucía Ramos-Alonso ◽  
Nadine Wittmaack ◽  
Isabel Mulet ◽  
Carlos A. Martínez-Garay ◽  
Josep Fita-Torró ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Saccharomyces Cerevisiae ◽  
Transcription Factor ◽  
Oxygen Consumption ◽  
Iron Accumulation

The expression of the constitutive Saccharomyces cerevisiae Aft1-1UP transcription factor increases iron accumulation, oxidative stress and iron-sensitivity, but diminishes oxygen consumption.

scholarly journals SET7/9-dependent methylation of ARTD1 at K508 stimulates poly-ADP-ribose formation after oxidative stress

Open Biology ◽  
2013 ◽  
Vol 3 (10) ◽  
pp. 120173 ◽  
Author(s):  
Ingrid Kassner ◽  
Anneli Andersson ◽  
Monika Fey ◽  
Martin Tomas ◽  
Elisa Ferrando-May ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein Interactions ◽  
Protein Function ◽  
Dependent Manner ◽  
Protein Protein Interactions ◽  
Post Translational Modification ◽  
Target Proteins ◽  
Protein Methyltransferase

ADP-ribosyltransferase diphtheria toxin-like 1 (ARTD1, formerly PARP1) is localized in the nucleus, where it ADP-ribosylates specific target proteins. The post-translational modification (PTM) with a single ADP-ribose unit or with polymeric ADP-ribose (PAR) chains regulates protein function as well as protein–protein interactions and is implicated in many biological processes and diseases. SET7/9 (Setd7, KMT7) is a protein methyltransferase that catalyses lysine monomethylation of histones, but also methylates many non-histone target proteins such as p53 or DNMT1. Here, we identify ARTD1 as a new SET7/9 target protein that is methylated at K508 in vitro and in vivo . ARTD1 auto-modification inhibits its methylation by SET7/9, while auto-poly-ADP-ribosylation is not impaired by prior methylation of ARTD1. Moreover, ARTD1 methylation by SET7/9 enhances the synthesis of PAR upon oxidative stress in vivo . Furthermore, laser irradiation-induced PAR formation and ARTD1 recruitment to sites of DNA damage in a SET7/9-dependent manner. Together, these results reveal a novel mechanism for the regulation of cellular ARTD1 activity by SET7/9 to assure efficient PAR formation upon cellular stress.

scholarly journals Luciferase-LOV BRET enables versatile and specific transcriptional readout of cellular protein-protein interactions

2019 ◽  
Author(s):  
Christina K. Kim ◽  
Kelvin F. Cho ◽  
Min Woo Kim ◽  
Alice Y. Ting
Keyword(s):  
Transcription Factor ◽  
Small Molecule ◽  
High Throughput ◽  
Protein Interactions ◽  
High Throughput Screening ◽  
Cellular Protein ◽  
Protein Protein Interactions ◽  
Lov Domain ◽  
Omics Technologies ◽  
Lower Background

Technologies that convert transient protein-protein interactions (PPIs) into stable expression of a reporter gene are useful for genetic selections, high-throughput screening, and multiplexing with omics technologies. We previously reported SPARK (Kim et al., 2017), a transcription factor that is activated by the coincidence of blue light and a PPI. Here, we report an improved, second-generation SPARK2 that incorporates a luciferase moiety to control the light-sensitive LOV domain. SPARK2 can be temporally gated by either external light or addition of a small-molecule luciferin, which causes luciferase to open LOV via proximity-dependent BRET. Furthermore, the nested “AND” gate design of SPARK2—in which both protease recruitment to the membrane-anchored transcription factor and LOV domain opening are regulated by the PPI of interest—yields a lower-background system and improved PPI specificity. We apply SPARK2 to high-throughput screening for GPCR agonists and for the detection of trans-cellular contacts, all with versatile transcriptional readout.

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