scholarly journals Xrp1 and Irbp18 trigger a feed-forward loop of proteotoxic stress to induce the loser status

PLoS Genetics ◽  
2021 ◽  
Vol 17 (12) ◽  
pp. e1009946
Author(s):  
Paul F. Langton ◽  
Michael E. Baumgartner ◽  
Remi Logeay ◽  
Eugenia Piddini
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
Stress Response ◽  
Oxidative Stress Response ◽  
Wild Type ◽  
Cell Competition ◽  
Feed Forward ◽  
Feed Forward Loop ◽  
Proteotoxic Stress

Cell competition induces the elimination of less-fit “loser” cells by fitter “winner” cells. In Drosophila, cells heterozygous mutant in ribosome genes, Rp/+, known as Minutes, are outcompeted by wild-type cells. Rp/+ cells display proteotoxic stress and the oxidative stress response, which drive the loser status. Minute cell competition also requires the transcription factors Irbp18 and Xrp1, but how these contribute to the loser status is partially understood. Here we provide evidence that initial proteotoxic stress in RpS3/+ cells is Xrp1-independent. However, Xrp1 is sufficient to induce proteotoxic stress in otherwise wild-type cells and is necessary for the high levels of proteotoxic stress found in RpS3/+ cells. Surprisingly, Xrp1 is also induced downstream of proteotoxic stress, and is required for the competitive elimination of cells suffering from proteotoxic stress or overexpressing Nrf2. Our data suggests that a feed-forward loop between Xrp1, proteotoxic stress, and Nrf2 drives Minute cells to become losers.

scholarly journals Xrp1 and Irbp18 trigger a feed-forward loop of proteotoxic stress to induce the loser status

2021 ◽  
Author(s):  
Paul F Langton ◽  
Michael E Baumgartner ◽  
Remi Logeay ◽  
Eugenia Piddini
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
Stress Response ◽  
Oxidative Stress Response ◽  
Wild Type ◽  
Cell Competition ◽  
Feed Forward ◽  
Feed Forward Loop ◽  
Proteotoxic Stress ◽  
Drosophila Cells

Cell competition induces the elimination of less-fit loser cells by fitter winner cells. In Drosophila, cells heterozygous mutant in ribosome genes, Rp/+, known as Minutes, are eliminated via cell competition by wild-type cells. Rp/+ cells display proteotoxic stress and the oxidative stress response, which drive the loser status. Minute cell competition also relies on the activities of the transcription factors Irbp18 and Xrp1, however how these contribute to the loser status is partially understood. Here, we show that Irbp18 and Xrp1 induce the loser status by promoting proteotoxic stress. We find that Xrp1 is necessary for Rp/+ -induced proteotoxic stress and is sufficient to induce proteotoxic stress in otherwise wild-type cells. Xrp1 is also induced downstream of proteotoxic stress and required for the competitive elimination of cells suffering from proteotoxic stress. Our data suggests that a feed-forward loop between Xrp1, proteotoxic stress, and Nrf2 drives Minute cells to become losers.

Clade III cytokinin response factors share common roles in response to oxidative stress responses linked to cytokinin synthesis

2021 ◽  
Vol 72 (8) ◽  
pp. 3294-3306
Author(s):  
Ariel M Hughes ◽  
H Tucker Hallmark ◽  
Lenka Plačková ◽  
Ondrej Novák ◽  
Aaron M Rashotte
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
Stress Response ◽  
Stress Responses ◽  
Oxidative Stress Response ◽  
Response Factors ◽  
Ontology Term ◽  
Regulated Expression ◽  
Cytokinin Response ◽  
Oxidative Stress Responses

Abstract Cytokinin response factors (CRFs) are transcription factors that are involved in cytokinin (CK) response, as well as being linked to abiotic stress tolerance. In particular, oxidative stress responses are activated by Clade III CRF members, such as AtCRF6. Here we explored the relationships between Clade III CRFs and oxidative stress. Transcriptomic responses to oxidative stress were determined in two Clade III transcription factors, Arabidopsis AtCRF5 and tomato SlCRF5. AtCRF5 was required for regulated expression of >240 genes that are involved in oxidative stress response. Similarly, SlCRF5 was involved in the regulated expression of nearly 420 oxidative stress response genes. Similarities in gene regulation by these Clade III members in response to oxidative stress were observed between Arabidopsis and tomato, as indicated by Gene Ontology term enrichment. CK levels were also changed in response to oxidative stress in both species. These changes were regulated by Clade III CRFs. Taken together, these findings suggest that Clade III CRFs play a role in oxidative stress response as well as having roles in CK signaling.

scholarly journals Increasing Oxygen Partial Pressures Induce a Distinct Transcriptional Response in Human PBMC: A Pilot Study on the “Normobaric Oxygen Paradox”

2021 ◽  
Vol 22 (1) ◽  
pp. 458
Author(s):  
Deborah Fratantonio ◽  
Fabio Virgili ◽  
Alessandro Zucchi ◽  
Kate Lambrechts ◽  
Tiziana Latronico ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
Stress Response ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Oxidative Stress Response ◽  
Molecular Characteristics ◽  
Nuclear Factor ◽  
Normobaric Oxygen ◽  
Oxygen Paradox

The term “normobaric oxygen paradox” (NOP), describes the response to the return to normoxia after a hyperoxic event, sensed by tissues as oxygen shortage, and resulting in up-regulation of the Hypoxia-inducible factor 1α (HIF-1α) transcription factor activity. The molecular characteristics of this response have not been yet fully characterized. Herein, we report the activation time trend of oxygen-sensitive transcription factors in human peripheral blood mononuclear cells (PBMCs) obtained from healthy subjects after one hour of exposure to mild (MH), high (HH) and very high (VHH) hyperoxia, corresponding to 30%, 100%, 140% O2, respectively. Our observations confirm that MH is perceived as a hypoxic stress, characterized by the activation of HIF-1α and Nuclear factor (erythroid-derived 2)-like 2 (NRF2), but not Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB). Conversely, HH is associated to a progressive loss of NOP response and to an increase in oxidative stress leading to NRF2 and NF-kB activation, accompanied by the synthesis of glutathione (GSH). After VHH, HIF-1α activation is totally absent and oxidative stress response, accompanied by NF-κB activation, is prevalent. Intracellular GSH and Matrix metallopeptidase 9 (MMP-9) plasma levels parallel the transcription factors activation pattern and remain elevated throughout the observation time. In conclusion, our study confirms that, in vivo, the return to normoxia after MH is sensed as a hypoxic trigger characterized by HIF-1α activation. On the contrary, HH and VHH induce a shift toward an oxidative stress response, characterized by NRF2 and NF-κB activation in the first 24 h post exposure.

scholarly journals Virulence of Streptococcus pneumoniae: PsaA Mutants Are Hypersensitive to Oxidative Stress

2002 ◽  
Vol 70 (3) ◽  
pp. 1635-1639 ◽  
Author(s):  
Hsing-Ju Tseng ◽  
Alastair G. McEwan ◽  
James C. Paton ◽  
Michael P. Jennings
Keyword(s):  
Oxidative Stress ◽  
Streptococcus Pneumoniae ◽  
Stress Response ◽  
Nadh Oxidase ◽  
Redox Homeostasis ◽  
Oxidative Stress Response ◽  
Wild Type ◽  
Regulation Of Expression ◽  
Altered Expression ◽  
Transport Complex

ABSTRACT psaA encodes a 37-kDa pneumococcal lipoprotein which is part of an ABC Mn(II) transport complex. Streptococcus pneumoniae D39 psaA mutants have previously been shown to be significantly less virulent than wild-type D39, but the mechanism underlying the attenuation has not been resolved. In this study, we have shown that psaA and psaD mutants are highly sensitive to oxidative stress, i.e., to superoxide and hydrogen peroxide, which might explain why they are less virulent than the wild-type strain. Our investigations revealed altered expression of the key oxidative-stress response enzymes superoxide dismutase and NADH oxidase in psaA and psaD mutants, suggesting that PsaA and PsaD may play important roles in the regulation of expression of oxidative-stress response enzymes and intracellular redox homeostasis.

scholarly journals Identification of ubiquitin Ser57 kinases regulating the oxidative stress response in yeast

2020 ◽  
Author(s):  
Nathaniel L. Hepowit ◽  
Kevin N. Pereira ◽  
Jessica M. Tumolo ◽  
Walter J. Chazin ◽  
Jason A. MacGurn
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Membrane Trafficking ◽  
Stress Responses ◽  
Protein Quality ◽  
Oxidative Stress Response ◽  
Post Translational Modifications ◽  
Cellular Processes ◽  
Proteotoxic Stress ◽  
Substrate Proteins

ABSTRACTUbiquitination regulates many different cellular processes, including protein quality control, membrane trafficking, and stress responses. The diversity of ubiquitin functions in the cell is partly due to its ability to form chains with distinct linkages that can alter the fate of substrate proteins in unique ways. The complexity of the ubiquitin code is further enhanced by post-translational modifications on ubiquitin itself, the biological functions of which are not well understood. Here, we present genetic and biochemical evidence that serine 57 (Ser57) phosphorylation of ubiquitin functions in stress responses in Saccharomyces cerevisiae, including the oxidative stress response. We also identify and characterize the first known Ser57 ubiquitin kinases in yeast and human cells, and we report that two Ser57 ubiquitin kinases regulate the oxidative stress response in yeast. These studies implicate ubiquitin phosphorylation at the Ser57 position as an important modifier of ubiquitin function, particularly in response to proteotoxic stress.

scholarly journals Kynurenine Metabolism Lifespan Extension Mediated by Oxidative Stress Response and Hypoxic Response in C. elegans

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 684-684
Author(s):  
Raul Castro-Portuguez ◽  
Jeremy Meyers ◽  
Sam Freitas ◽  
Hope Dang ◽  
Emily Turner ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
Stress Response ◽  
Aging Process ◽  
De Novo ◽  
Kynurenine Pathway ◽  
Oxidative Stress Response ◽  
Lifespan Extension ◽  
Hypoxic Stress ◽  
C Elegans

Abstract Aging is characterized by a progressive decline in the normal physiological functions of an organism, ultimately leading to mortality. Metabolic changes throughout the aging process disrupt the balance and homeostasis of the cell. The kynurenine metabolic pathway is the sole de novo biosynthetic pathway for producing NAD+ from ingested tryptophan. Altered kynurenine pathway activity is associated with both aging and a variety of age-associated diseases, and kynurenine-based interventions can extend lifespan in Caenorhabditis elegans. Our laboratory recently demonstrated knockdown of the kynurenine pathway enzymes kynureninase (KYNU) or 3-hydroxyanthranilic acid dioxygenase (HAAO) increases lifespan by 20-30% in C elegans. However, the mechanism of how these interventions may modulate response against different stressors during the aging process has yet to be explored. Fluorescent reporter strains show the stress-responsive transcription factors skn-1 (ortholog of NRF2/NFE2L2; oxidative stress response) and hif-1 (ortholog of HIF1A; hypoxic stress response) to be highly upregulated when the kynurenine pathway is inhibited. We also demonstrated the increase expression of gst-4 and gcs-1 (transcriptional targets skn-1), which are involved in production of the antioxidant glutathione (GSH), as well as upregulation of cysl-2 (transcriptional target of hif-1), a regulator of cysteine biosynthesis from serine. We hypothesize that lifespan extension resulting from kynurenine pathway inhibition is mediated, at least in part, by upregulation of these transcription factors, providing elevated defense against oxidative stress and hypoxic stress.

scholarly journals Transcriptional Response of Leptospira interrogans to Iron Limitation and Characterization of a PerR Homolog

2010 ◽  
Vol 78 (11) ◽  
pp. 4850-4859 ◽  
Author(s):  
Miranda Lo ◽  
Gerald L. Murray ◽  
Chen Ai Khoo ◽  
David A. Haake ◽  
Richard L. Zuerner ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Iron Homeostasis ◽  
Storage Proteins ◽  
Iron Acquisition ◽  
Bacterial Species ◽  
Transcriptional Response ◽  
Oxidative Stress Response ◽  
Wild Type ◽  
In The Wild

ABSTRACT Leptospirosis is a globally significant zoonosis caused by Leptospira spp. Iron is essential for growth of most bacterial species. Since iron availability is low in the host, pathogens have evolved complex iron acquisition mechanisms to survive and establish infection. In many bacteria, expression of iron uptake and storage proteins is regulated by Fur. L. interrogans encodes four predicted Fur homologs; we have constructed a mutation in one of these, la1857. We conducted microarray analysis to identify iron-responsive genes and to study the effects of la1857 mutation on gene expression. Under iron-limiting conditions, 43 genes were upregulated and 49 genes were downregulated in the wild type. Genes encoding proteins with predicted involvement in inorganic ion transport and metabolism (including TonB-dependent proteins and outer membrane transport proteins) were overrepresented in the upregulated list, while 54% of differentially expressed genes had no known function. There were 16 upregulated genes of unknown function which are absent from the saprophyte L. biflexa and which therefore may encode virulence-associated factors. Expression of iron-responsive genes was not significantly affected by mutagenesis of la1857, indicating that LA1857 is not a global regulator of iron homeostasis. Upregulation of heme biosynthetic genes and a putative catalase in the mutant suggested that LA1857 is more similar to PerR, a regulator of the oxidative stress response. Indeed, the la1857 mutant was more resistant to peroxide stress than the wild type. Our results provide insights into the role of iron in leptospiral metabolism and regulation of the oxidative stress response, including genes likely to be important for virulence.

scholarly journals Calcium-binding protein 39 facilitates molecular interaction between Ste20p proline alanine-rich kinase and oxidative stress response 1 monomers

2012 ◽  
Vol 303 (11) ◽  
pp. C1198-C1205 ◽  
Author(s):  
José Ponce-Coria ◽  
Kenneth B. Gagnon ◽  
Eric Delpire
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Calcium Binding ◽  
Binding Protein ◽  
Oxidative Stress Response ◽  
Calcium Binding Protein ◽  
Domain Swapping ◽  
Xenopus Laevis Oocytes ◽  
Wild Type ◽  
Kinase Activation

X-ray crystallography of the catalytic domain of oxidative stress response 1 (OSR1) has provided evidence for dimerization and domain swapping. However, the functional significance of dimer formation or domain swapping has yet to be addressed. In this study, we used nine glutamine residues to link the carboxyl end of one SPAK (related Ste20 kinase) monomer to the amino end of another SPAK monomer to assess the role of kinase monomers versus dimers in Na-K-2Cl cotransporter 1 (NKCC1) activation. Transport studies in Xenopus laevis oocytes show that forcing dimerization of two wild-type SPAK molecules results in cotransporter activation when calcium-binding protein 39 (Cab39) is coexpressed, indicating that the presence of Cab39 can bypass the upstream phosphorylation requirement of SPAK normally associated with kinase activation. We determined that monomers are the functional units of the kinase as concatamers consisting of an active and various inactive monomers were still functional. Furthermore, we found that two different nonfunctional SPAK mutants could be linked together in a concatamer and activated, presumably by domain swapping, indicating that dimerization and domain swapping are both important components of kinase activation. Finally, we demonstrate rescue of a nonfunctional SPAK mutant by domain swapping with wild-type OSR1, indicating that heterodimers of the two Ste20-related kinases are possible and therefore potentially relevant to the regulation of NKCC1 activity.

scholarly journals Bach1Deficiency and Accompanying Overexpression of Heme Oxygenase-1 Do Not Influence Aging or Tumorigenesis in Mice

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Kazushige Ota ◽  
Andrey Brydun ◽  
Ari Itoh-Nakadai ◽  
Jiying Sun ◽  
Kazuhiko Igarashi
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Heme Oxygenase ◽  
Transcriptional Activity ◽  
Oxidative Stress Response ◽  
Acute Injury ◽  
Heme Oxygenase 1 ◽  
Wild Type ◽  
Environmental Perturbations ◽  
Deficient Mice

Oxidative stress contributes to both aging and tumorigenesis. The transcription factor Bach1, a regulator of oxidative stress response, augments oxidative stress by repressing the expression of heme oxygenase-1 (HO-1) gene (Hmox1) and suppresses oxidative stress-induced cellular senescence by restricting the p53 transcriptional activity. Here we investigated the lifelong effects ofBach1deficiency on mice.Bach1-deficient mice showed longevity similar to wild-type mice. Although HO-1 was upregulated in the cells ofBach1-deficient animals, the levels of ROS inBach1-deficient HSCs were comparable to those in wild-type cells.Bach1−/−;p53−/−mice succumbed to spontaneous cancers as frequently asp53-deficient mice.Bach1deficiency significantly altered transcriptome in the liver of the young mice, which surprisingly became similar to that of wild-type mice during the course of aging. The transcriptome adaptation toBach1deficiency may reflect how oxidative stress response is tuned upon genetic and environmental perturbations. We concluded thatBach1deficiency and accompanying overexpression of HO-1 did not influence aging or p53 deficiency-driven tumorigenesis. Our results suggest that it is useful to target Bach1 for acute injury responses without inducing any apparent deteriorative effect.

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