scholarly journals The Regulatory Functions of σ54 Factor in Phytopathogenic Bacteria

2021 ◽  
Vol 22 (23) ◽  
pp. 12692
Author(s):  
Chao Yu ◽  
Fenghuan Yang ◽  
Dingrong Xue ◽  
Xiuna Wang ◽  
Huamin Chen
Keyword(s):  
Bacterial Growth ◽  
Regulatory Network ◽  
Regulatory Role ◽  
Regulatory Function ◽  
Dependent Manner ◽  
Phytopathogenic Bacteria ◽  
Regulatory Pathways ◽  
World Food Security ◽  
Complex Regulatory Network

σ54 factor (RpoN), a type of transcriptional regulatory factor, is widely found in pathogenic bacteria. It binds to core RNA polymerase (RNAP) and regulates the transcription of many functional genes in an enhancer-binding protein (EBP)-dependent manner. σ54 has two conserved functional domains: the activator-interacting domain located at the N-terminal and the DNA-binding domain located at the C-terminal. RpoN directly binds to the highly conserved sequence, GGN10GC, at the −24/−12 position relative to the transcription start site of target genes. In general, bacteria contain one or two RpoNs but multiple EBPs. A single RpoN can bind to different EBPs in order to regulate various biological functions. Thus, the overlapping and unique regulatory pathways of two RpoNs and multiple EBP-dependent regulatory pathways form a complex regulatory network in bacteria. However, the regulatory role of RpoN and EBPs is still poorly understood in phytopathogenic bacteria, which cause economically important crop diseases and pose a serious threat to world food security. In this review, we summarize the current knowledge on the regulatory function of RpoN, including swimming motility, flagella synthesis, bacterial growth, type IV pilus (T4Ps), twitching motility, type III secretion system (T3SS), and virulence-associated phenotypes in phytopathogenic bacteria. These findings and knowledge prove the key regulatory role of RpoN in bacterial growth and pathogenesis, as well as lay the groundwork for further elucidation of the complex regulatory network of RpoN in bacteria.

C/EBPβ and GATA-1 Synergistically Regulate Activity of the Eosinophil Granule Major Basic Protein Promoter: Implication for C/EBPβ Activity in Eosinophil Gene Expression

Blood ◽  
1999 ◽  
Vol 94 (4) ◽  
pp. 1429-1439 ◽  
Author(s):  
Yuji Yamaguchi ◽  
Hitoshi Nishio ◽  
Kenji Kishi ◽  
Steven J. Ackerman ◽  
Toshio Suda
Keyword(s):  
Binding Site ◽  
Cell Line ◽  
Binding Sites ◽  
Basic Protein ◽  
Regulatory Role ◽  
Expression Vectors ◽  
Regulatory Function ◽  
Dependent Manner ◽  
Major Basic Protein ◽  
Eosinophil Granule

Abstract Eosinophil granule major basic protein (MBP) is expressed exclusively in eosinophils and basophils in hematopoietic cells. In our previous study, we demonstrated a major positive regulatory role for GATA-1 and a negative regulatory role for GATA-2 in MBP gene transcription. Further analysis of the MBP promoter region identified a C/EBP (CCAAT/enhancer-binding protein) consensus binding site 6 bp upstream of the functional GATA-binding site in the MBP gene. In the cell line HT93A, which is capable of differentiating towards both the eosinophil and neutrophil lineages in response to retinoic acid (RA), C/EBP mRNA expression decreased significantly concomitant with eosinophilic and neutrophilic differentiation, whereas C/EBPβ expression was markedly increased. Electrophoretic mobility shift assays (EMSAs) showed that recombinant C/EBPβ protein could bind to the potential C/EBP-binding site (bp −90 to −82) in the MBP promoter. Furthermore, we have demonstrated that both C/EBPβ and GATA-1 can bind simultaneously to the C/EBP- and GATA-binding sites in the MBP promoter. To determine the functionality of both the C/EBP- and GATA-binding sites, we analyzed whether C/EBPβ and GATA-1 can stimulate the MBP promoter in the C/EBPβ and GATA-1 negative Jurkat T-cell line. Cotransfection with C/EBPβ and GATA-1 expression vectors produced a 5-fold increase compared with cotransfection with the C/EBPβ or GATA-1 expression vectors individually. In addition, GST pull-down experiments demonstrated a physical interaction between human GATA-1 and C/EBPβ. Expression of FOG (F̲riendo̲fG̲ATA), which binds to GATA-1 and acts as a cofactor for GATA-binding proteins, decreased transactivation activity of GATA-1 for the MBP promoter in a dose-dependent manner. Our results provide the first evidence that both GATA-1 and C/EBPβ synergistically transactivate the promoter of an eosinophil-specific granule protein gene and that FOG may act as a negative cofactor for the eosinophil lineage, unlike its positively regulatory function for the erythroid and megakaryocyte lineages.

scholarly journals Novel Strategy for Improvement of the Bioleaching Efficiency of Acidithiobacillus ferrooxidans Based on the AfeI/R Quorum Sensing System

Minerals ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 222 ◽  
Author(s):  
Xue-Yan Gao ◽  
Xiu-Jie Liu ◽  
Chang-Ai Fu ◽  
Xiu-Feng Gu ◽  
Jian-Qiang Lin ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Acidithiobacillus Ferrooxidans ◽  
Extracellular Polymeric Substances ◽  
Genetic Manipulation ◽  
Regulatory Function ◽  
Regulatory Pathways ◽  
Sensing System ◽  
Quorum Sensing System ◽  
Novel Strategy

Acidithiobacillus ferrooxidans is an acidophilic and chemolithotrophic sulfur- and iron-oxidizing bacterium that has been widely used in the bioleaching process for extracting metals. Extracellular polymeric substances (EPS) are essential for bacteria-ore interactions, and the regulation of EPS synthesis could be an important way of influencing the efficiency of the bioleaching process. Therefore, exploring and utilizing the regulatory pathways of EPS synthesis to improve the bacterial bioleaching capability have posed a challenge in the study and application of bioleaching bacteria. Here, several engineering strains were constructed using genetic manipulation methods. And we revealed the regulatory function of the AfeI/R quorum sensing (QS) system in EPS synthesis and biofilm formation of A. ferrooxidans, and the AfeI/R-mediated EPS synthesis could influence bacteria-substrate interactions and the efficiency of bioleaching. Finally, an AfeI/R-mediated bioleaching model was proposed to illustrate the role of QS system in this process. This study provided new insights into and clues for developing highly efficient bioleaching bacteria and modulating the bioleaching process.

scholarly journals Oncogenic Landscape of Somatic Mutations Perturbing Pan-Cancer lncRNA-ceRNA Regulation

2021 ◽  
Vol 9 ◽  
Author(s):  
Yuanfu Zhang ◽  
Peng Han ◽  
Qiuyan Guo ◽  
Yangyang Hao ◽  
Yue Qi ◽  
...  
Keyword(s):  
Regulatory Network ◽  
Somatic Mutations ◽  
Low Frequency ◽  
Oncogenic Signaling ◽  
Regulatory Pathways ◽  
Multiple Cancers ◽  
Competing Endogenous Rnas ◽  
Cancer Types ◽  
Significant Mechanism

Competing endogenous RNAs (ceRNA) are transcripts that communicate with and co-regulate each other by competing for the binding of shared microRNAs (miRNAs). Long non-coding RNAs (lncRNAs) as a type of ceRNA constitute a competitive regulatory network determined by miRNA response elements (MREs). Mutations in lncRNA MREs destabilize their original regulatory pathways. Study of the effects of lncRNA somatic mutations on ceRNA mechanisms can clarify tumor mechanisms and contribute to the development of precision medicine. Here, we used somatic mutation profiles collected from TCGA to characterize the role of lncRNA somatic mutations in the ceRNA regulatory network in 33 cancers. The 31,560 mutation sites identified by TargetScan and miRanda affected the balance of 70,811 ceRNA regulatory pathways. Putative mutations were categorized as high or low based on mutation frequencies. Multivariate multiple regression revealed a significant effect of 162 high-frequency mutations in six cancer types on the expression levels of target mRNAs (ceMs) through the ceRNA mechanism. Low-frequency mutations in multiple cancers perturbing 1624 ceM have been verified by Student’s t-test, indicating a significant mechanism of changes in the expression level of oncogenic genes. Oncogenic signaling pathway studies involving ceMs indicated functional heterogeneity of multiple cancers. Furthermore, we identified that lncRNA, perturbing ceMs associated with patient survival, have potential as biomarkers. Our collective findings revealed individual differences in somatic mutations perturbing ceM expression and impacting tumor heterogeneity.

scholarly journals Immunomodulatory effects of probiotics

2020 ◽  
pp. 135-144
Author(s):  
E. Yu. Plotnikova ◽  
Yu. V. Zakharova
Keyword(s):  
Immune System ◽  
Intestinal Microbiota ◽  
Regulatory Role ◽  
Regulatory Pathways ◽  
Intestinal Microbes ◽  
Beneficial Effects ◽  
Susceptibility To Infection ◽  
Key Species ◽  
Mucous Membranes

Today, there is an explosion of discoveries related to a growing understanding of the role of microbial communities, key species of bacteria, products or metabolites derived from commensals, and in particular the relationship between some of these components and painful conditions in humans. Microbiota plays a fundamental role in the induction, training and functioning of the host’s immune system. In turn, the immune system has evolved significantly as a means of maintaining the host’s symbiotic relations with these very diverse and developing microbes. At optimal performance, this alliance of the immune system and microbiota allows to induce protective reactions to pathogens and maintain regulatory pathways involved in maintaining tolerance to harmless antigens. In this review, we outline the role of the intestinal microbiota in the immune system, starting with initial information supporting further insights into the effects of intestinal microbiota dysbacteriosis on the host’s susceptibility to infection. Probiotics are considered a good form of therapy to control harmful intestinal microorganisms, improve digestion and the absorption of nutrients. The beneficial effects of probiotics have been demonstrated in many diseases. One of the main mechanisms of probiotics is the regulation of the immune response of the host. The article reviews and discusses the regulatory role of probiotics in the “intestine-lungs” system and the immune system of mucous membranes for potential antiviral mechanisms. The unique role of probiotics in modulation of intestinal microbes and establishment of intestinal homeostasis and production of interferon as antiviral mechanism is described. In addition, the regulatory role of probiotics in the system «intestine-lungs» and the immune system of the mucous membranes for potential antiviral mechanisms, including in COVID-19 is considered and discussed. Symbiotic products Bac-Set® Forte and Bac-Set® Cold/Flu are described.

scholarly journals CRZ1 regulator and calcium cooperatively modulate holocellulases gene expression in Trichoderma reesei QM6a

2019 ◽  
Author(s):  
Leonardo Martins-Santana ◽  
Renato Graciano de Paula ◽  
Adriano Gomes Silva ◽  
Douglas Christian Borges Lopes ◽  
Roberto do Nascimento Silva ◽  
...  
Keyword(s):  
Gene Expression ◽  
Trichoderma Reesei ◽  
Regulatory Network ◽  
Plant Biomass ◽  
Transcriptional Regulators ◽  
Regulatory Role ◽  
Cellulolytic Enzymes ◽  
Strong Increase ◽  
New Evidence

AbstractBackgroundTrichoderma reesei is the main filamentous fungus used in industry to produce cellulases. Over the last decades, there have been a strong increase in the understanding of the regulatory network controlling cellulase-coding gene expression in response to a number of inducers and environmental signals. In this sense, the role of calcium and the Calcineurin-responsive protein (CRZ1) has been investigated in industrially relevant strains of T. reesei RUT-C30, but this system has not been investigated in wild-type reference strain of this fungus.ResultsHere, we investigated the role of CRZ1 and Ca2+ signaling in the fungus T. reesei QM6a. For this, we first searched for potential CRZ1 binding sites in promoter regions of key genes coding holocellulases, as well as transcriptional regulators and sugar and calcium transporters. Using a nearly constructed T. reesei Δcrzl strain, we demonstrated that most of the genes expected to be regulated by CRZ1 were affected in the mutant strain induced with sugarcane bagasse (SCB) and cellulose. In particular, our data demonstrate that Ca2+ acts synergistically with CRZ1 to modulate gene expression, but also exerts CRZ1-independent regulatory role in gene expression in T. reesei, suggesting the existence of additional Ca2+ sensing mechanisms in this fungus.ConclusionsThis work presents new evidence on the regulatory role of CRZ1 and Ca2+ sensing in the regulation of cellulolytic enzymes in T. reesei, evidencing significant and previously unknown function of this Ca2+ sensing system in the control key transcriptional regulators (XYR1 and CRE1) and on the expression of genes related to sugar and Ca2+ transport. Taken together, the data obtained here provide new evidence on the regulatory network of T. reesei related to plant biomass deconstruction.

scholarly journals Regulation of PP2A, PP4, and PP6 holoenzyme assembly by carboxyl-terminal methylation

2021 ◽  
Author(s):  
Scott P. Lyons ◽  
Elora C. Greiner ◽  
Lauren E. Cressey ◽  
Mark E. Adamo ◽  
Arminja N. Kettenbach
Keyword(s):  
Cell Lines ◽  
Regulatory Subunit ◽  
Regulatory Function ◽  
Dependent Manner ◽  
Catalytic Subunits ◽  
Transformed Cell ◽  
The Family ◽  
Carboxyl Terminal ◽  
Transformed Cell Lines

The family of Phosphoprotein Phosphatases (PPPs) is responsible for most cellular serine and threonine dephosphorylation. PPPs achieve substrate specificity and selectivity by forming multimeric holoenzymes. PPP holoenzyme assembly is tightly controlled, and changes in the cellular repertoire of PPPs are linked to human disease, including cancer and neurodegeneration. For PP2A, PP4, and PP6, holoenzyme formation is in part regulated by carboxyl (C)-terminal methyl-esterification (often referred to as methylation). Here, we use mass spectrometry-based proteomics, methylation-ablating mutations, and genome editing to elucidate the role of C-terminal methylation on PP2A, PP4, and PP6 holoenzyme assembly. We find that the catalytic subunits of PP2A, PP4, and PP6 are frequently methylated in cancer cells and that deletion of the C-terminal leucine faithfully recapitulates loss of methylation. We observe that loss of PP2A methylation consistently reduced B55, B56, and B72 regulatory subunit binding in cancer and non-transformed cell lines. However, Striatin subunit binding is only affected in non-transformed cells. For PP4, we find that PP4R1 and PP4R3β bind in a methylation-dependent manner. Intriguingly, loss of methylation does not affect PP6 holoenzymes. Our analyses demonstrate in an unbiased, comprehensive, and isoform-specific manner the crucial regulatory function of endogenous PPP methylation in transformed and non-transformed cell lines.

scholarly journals Steroid hormones modulate galectin-1 in the trophoblast HTR-8/SVneocell line

2008 ◽  
Vol 60 (1) ◽  
pp. 11-23 ◽  
Author(s):  
Zanka Bojic-Trbojevic ◽  
Milica Bozic ◽  
Ljiljana Vicovac
Keyword(s):  
Steroid Hormones ◽  
Cell Invasion ◽  
Regulatory Role ◽  
Dependent Manner ◽  
Data Support ◽  
Low Concentrations ◽  
Dose Dependent

The effects of steroids on galectin-1 (gal-1) were studied in HTR-8/SVneo cells by immunocytochemistry, cell-based ELISA, the MTT proliferation test and the Matrigel TM invasion test. Dexamethasone (DEX), progesterone (PRG), and mifepristone (RU486) were used. Gal-1 was modulated in a steroid- and dose-dependent manner by DEX, which mildly but significantly stimulated production at low concentrations (0.1-10 nM), and inhibited it at 100 nM, while the effects of PRG and RU486 were opposite. HTR-8/SVneo cell invasion of Matrigel was significantly decreased in the presence of DEX and lactose. The obtained data support the proposed regulatory role of steroids in trophoblast gal-1 production.

scholarly journals A Potential Probiotic for Diarrhea: Clostridium tyrobutyricum Protects Against LPS-Induced Epithelial Dysfunction via IL-22 Produced By Th17 Cells in the Ileum

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhiping Xiao ◽  
Lujie Liu ◽  
Xun Pei ◽  
Wanjing Sun ◽  
Yuyue Jin ◽  
...  
Keyword(s):  
Th17 Cells ◽  
Intestinal Inflammation ◽  
Flow Cytometric Analysis ◽  
Protective Role ◽  
Regulatory Function ◽  
Clostridium Tyrobutyricum ◽  
Dependent Manner ◽  
Protective Function

Probiotics are clinically used for diarrhea and inflammatory bowel diseases in both humans and animals. Previous studies have shown that Clostridium tyrobutyricum (Ct) protects against intestinal dysfunction, while its regulatory function in the gut needs further investigation and the related mechanisms are still not fully elucidated. This study aims to further verify the protective function of Ct and reveal its underlying mechanisms in alleviating diarrhea and intestinal inflammation. Ct inhibited LPS-induced diarrhea and intestinal inflammation in the ileum. IL-22 was identified and the protective role of Ct in the ileum presented an IL-22-dependent manner according to the transcriptomic analysis and in vivo interference mice experiments. The flow cytometric analysis of immune cells in the ileum showed that Ct enhanced the proportions of Th17 cells in response to LPS. The results of in situ hybridization further verified that Ct triggered Th17 cells to produce IL-22, which combined with IL-22RA1 expressed in the epithelial cells. Moreover, Ct was unable to enhance the levels of short-chain fatty acids (SCFAs) in the ileum, suggesting that the protective role of Ct in the ileum was independent of SCFAs. This study uncovered the role of Ct in alleviating diarrhea and inflammation with the mechanism of stimulating Th17 cells in the lamina propria to produce IL-22, highlighting its potential application as a probiotic for diarrhea and inflammation in the ileum.

scholarly journals Regulatory role of sphingolipid metabolites, sphingosine-1-phosphate and C16:0 ceramide, in immunogenic cell death of colon cancer cells induced by Bak/Bax-activation.

2021 ◽  
Author(s):  
Jeremy A. Hengst ◽  
Asvelt J. Nduwumwami ◽  
Jong K. Yun
Keyword(s):  
Colon Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Chemotherapeutic Agents ◽  
Regulatory Role ◽  
Immunogenic Cell Death ◽  
Dependent Manner ◽  
Colon Cancer Cells ◽  
Sphingosine 1 Phosphate

We have previously identified sphingolipid metabolism as a key intracellular process associated with immunogenic cell death (ICD) induced by mitoxantrone in colon cancer cells. Specifically, we have demonstrated that inhibition of the sphingosine kinases (SphKs) synergistically enhanced production of hallmarks of ICD including ectoCRT production. To better understand the mechanism associated with ICD enhanced by SphK1-inhibition, we focused on the ER stress-associated intracellular signaling pathways leading to ectoCRT production. It is known that ABT-263 and AZD-5991 (ABT/AZD) are inhibitors of Bcl-2/Bcl-XL and MCL-1, respectively, leading to activation of Bak/Bax. Herein, we now provide evidence that treatment of DLD-1 colon cancer cells with ABT/AZD results in the production of ectoCRT indicative of ICD. Additionally, our data show that ABT/AZD-induced ectoCRT production is significantly enhanced by combination treatment with the SphK1 inhibitor, PF-543. Mechanistically, we demonstrate that combined treatment of ABT/AZD+PF-543 induces ectoCRT exposure in a caspase 8-dependent manner. Accordingly, we have identified a Bak/Bax activation-dependent pathway that leads to activation of a pro-survival SphK1/sphingosine-1-phosphate (S1P) signaling that attenuates ectoCRT production. Additionally, we have identified a regulatory role of ceramide synthase 6 (CerS6)-C16:0 Cer in transporting of dimeric CRT to the cell surface (ectoCRT). Together, these results indicate that sphingolipid metabolites, such as S1P and C16:0 Cer, have a key regulatory role for survival/death decisions of cancer cells in response to ICD-inducing chemotherapeutic agents such as mitoxantrone and ABT/AZD. Hence, targeting SphKs may be an innovative means to enhance the efficacy of ICD-inducing chemotherapeutic agents promoting anti-tumor innate/adaptive immune response since SphK inhibition blocks the anti-ICD effects of S1P while simultaneously accumulating sphingosine (Sph) leading to pro-ICD C16:0 Cer synthesis.

scholarly journals A Genome-wide microRNA screen identifies the microRNA-183/96/182 cluster as a modulator of circadian rhythms

2020 ◽  
Author(s):  
Lili Zhou ◽  
Caitlyn Miller ◽  
Loren J. Miraglia ◽  
Angelica Romero ◽  
Ludovic S. Mure ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Circadian Clock ◽  
Luciferase Reporter ◽  
Regulatory Function ◽  
Mirna Cluster ◽  
Dependent Manner ◽  
Genome Wide ◽  
A Genome

AbstractThe regulatory mechanisms of circadian rhythms have been studied primarily at the level of the transcription-translation feedback loops of protein coding genes. Regulatory modules involving non-coding RNAs are less thoroughly understood. In particular, emerging evidence has revealed the important role of miRNAs in maintaining the robustness of the circadian system. To identify miRNAs that have the potential to modulate circadian rhythms, we conducted a genome-wide miRNA screen using U2OS luciferase reporter cells. Among 989 miRNAs in the library, 120 changed the period length in a dosage-dependent manner. We further validated the circadian regulatory function of a miRNA cluster, miR-183/96/182, both in vitro and in vivo. We found that all three members of this miRNA cluster can modulate circadian rhythms. Particularly, miR-96 directly targeted a core circadian clock gene, PER2. The knockout of the miR-183/96/182 cluster in mice showed tissue-specific effects on circadian parameters and altered circadian rhythms at the behavioral level. This study identified a large number of miRNAs, including the miR-183/96/182 cluster, as circadian modulators. We provide a resource for further understanding the role of miRNAs in the circadian network and highlight the importance of miRNAs as a novel genome-wide layer of circadian clock regulation.Significance StatementAlthough miRNAs are emerging as important regulators of diverse physiological and pathological processes, our knowledge of their potential role in regulation of circadian rhythms is still limited. We deployed a cell-based genome-wide screening approach, and successfully identified mature miRNAs as cell-autonomous circadian modulators. We then specifically focused on the miR-183/96/182 cluster among the candidate miRNA hits and revealed their circadian function both in vitro and in vivo from the unbiased screen. This study provides resources for further understanding the role of miRNAs in the circadian network. It also highlights the importance of miRNAs as a novel genome-wide layer of circadian clock regulation.

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