Multiple roles for Gata5 in zebrafish endoderm formation

Development ◽  
2001 ◽  
Vol 128 (1) ◽  
pp. 125-135 ◽  
Author(s):  
J.F. Reiter ◽  
Y. Kikuchi ◽  
D.Y. Stainier
Keyword(s):  
Transcription Factor ◽  
Multiple Roles ◽  
Nodal Signaling ◽  
Wild Type ◽  
Transcription Factor Gene ◽  
Endoderm Development ◽  
Additional Support ◽  
Endodermal Cells ◽  
Relationship Of ◽  
The Relationship

Previous studies have indicated that gata5, a zinc-finger transcription factor gene, is required for the development of the zebrafish gut tube. Here, we show that gata5 mutants also display defects in the development of other endodermal organs such as the liver, pancreas, thyroid and thymus. gata5 is expressed in the endodermal progenitors from late blastula stages, suggesting that it functions early during endoderm development. We indeed find that during gastrulation stages, gata5 mutants form fewer endodermal cells than their wild-type siblings. In addition, the endodermal cells that form in gata5 mutants appear to express lower than wild-type levels of endodermal genes such as sox17 and axial/foxA2. Conversely, overexpression of gata5 leads to expanded endodermal gene expression. These data indicate that Gata5 is involved both in the generation of endodermal cells at late blastula stages and in the maintenance of endodermal sox17 expression during gastrulation. We have also analyzed the relationship of Gata5 to other factors involved in endoderm formation. Using complementary mutant and overexpression analyses, we show that Gata5 regulates endoderm formation in cooperation with the Mix-type transcription factor Bon, that Gata5 and Bon function downstream of Nodal signaling, and that cas function is usually required for the activity of Gata5 in endoderm formation. Finally, we show that fau/gata5, bon and cas exhibit dominant genetic interactions providing additional support that they function in the same pathway. Together, these data demonstrate that Gata5 plays multiple roles in endoderm development in zebrafish, and position Gata5 relative to other regulators of endoderm formation.

scholarly journals ClpP Modulates the Activity of the Bacillus subtilis Stress Response Transcription Factor, σB

2007 ◽  
Vol 189 (17) ◽  
pp. 6168-6175 ◽  
Author(s):  
Adam Reeves ◽  
Ulf Gerth ◽  
Uwe Völker ◽  
W. G. Haldenwang
Keyword(s):  
Transcription Factor ◽  
Bacillus Subtilis ◽  
Nutritional Stress ◽  
Physical Stress ◽  
Adaptive Responses ◽  
Wild Type ◽  
Marked Enhancement ◽  
Activity State ◽  
Relationship Of ◽  
The Relationship

ABSTRACT The general stress regulon of Bacillus subtilis is controlled by the activity state of σB, a transcription factor that is switched on following exposure to either physical or nutritional stress. ClpP is the proteolytic component of an ATP-dependent protease that is essential for the proper regulation of multiple adaptive responses in B. subtilis. Among the proteins whose abundance increases in ClpP− B. subtilis are several known to depend on σB for their expression. In the current work we examine the relationship of ClpP to the activity of σB. The data reveal that the loss of ClpP in otherwise wild-type B. subtilis results in a small increase in σB activity during growth and a marked enhancement of σB activity following its induction by either physical or nutritional stress. It appears to be the persistence of σB's activity rather than its induction that is principally affected by the loss of ClpP. σB-dependent reporter gene activity rose in parallel in ClpP+ and ClpP− B. subtilis strains but failed to display its normal transience in the ClpP− strain. The putative ClpP targets are likely to be stress generated and novel. Enhanced σB activity in ClpP− B. subtilis was triggered by physical stress but not by the induced synthesis of the physical stress pathway's positive regulator (RsbT). In addition, Western blot analyses failed to detect differences in the levels of the principal known σB regulators in ClpP+ and ClpP− B. subtilis strains. The data suggest a model in which ClpP facilitates the turnover of stress-generated factors, which persist in ClpP's absence to stimulate ongoing σB activity.

Relationship of the cGMP-binding activity to the cGMP-specific phosphodiesterase in Dictyostelium discoideum

1986 ◽  
Vol 64 (6) ◽  
pp. 528-534 ◽  
Author(s):  
A. M. Parissenti ◽  
M. B. Coukell
Keyword(s):  
Dictyostelium Discoideum ◽  
Kinase Activity ◽  
Deae Cellulose ◽  
Binding Activity ◽  
Wild Type ◽  
Dependent Protein ◽  
Low Levels ◽  
Relationship Of ◽  
The Relationship ◽  
Type Strains

Optimal conditions for assaying and stabilizing the soluble cGMP-binding activity in Dictyostelium discoideum were established. Using these procedures, we investigated the relationship between the cGMP-binding activity and the cGMP-specific phosphodiesterase in this organism. In wild-type strains, the binding and phosphodiesterase activities were found to be regulated differently during development. Also, stmF mutants, which possess very low levels of cGMP-specific phosphodiesterase activity, exhibited normal levels of cGMP-binding activity. Fractionation studies revealed that the binding and phosphodiesterase activities could be resolved by DEAE-cellulose chromatography. Finally, the effect of pH on cGMP binding was different from that reported for cGMP-mediated activation of the phosphodiesterase. Taken together, these results indicate that the cGMP-binding protein and the cGMP-specific phosphodiesterase are probably unrelated. In addition, the cGMP-binding activity is not associated with cGMP-stimulated kinase activity and it does not elute from DEAE-cellulose like the highly conserved cGMP-dependent protein kinases found in other systems.

scholarly journals Mapping of the inducible IkappaB phosphorylation sites that signal its ubiquitination and degradation.

1996 ◽  
Vol 16 (4) ◽  
pp. 1295-1304 ◽  
Author(s):  
J DiDonato ◽  
F Mercurio ◽  
C Rosette ◽  
J Wu-Li ◽  
H Suyang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Tumor Necrosis ◽  
Interleukin 1 ◽  
Phosphorylation Sites ◽  
Wild Type ◽  
Rapid Degradation ◽  
Extracellular Stimuli ◽  
Nf Kappab ◽  
The Relationship ◽  
Necrosis Factor

Extracellular stimuli that activate the transcription factor NF-kappaB cause rapid phosphorylation of the IkappaBalpha inhibitor, which retains NF-kappaB in the cytoplasm of nonstimulated cells. Phosphorylation of IkappaBalpha is followed by its rapid degradation, the inhibition of which prevents NF-kappaB activation. To determine the relationship between these events, we mapped the inducible phosphorylation sites of IkappaBalpha. We found that two residues, serines 32 and 36, were phosphorylated in response to either tumor necrosis factor, interleukin-1, or phorbol ester. Substitution of either serine blocks or slows down induction of IkappaBalpha degradation. Substitutions of the homologous sites in IkappaBbeta, serines 19 and 23, also prevent inducible IkappaBbeta degradation. We suggest that activation of a single IkappaB kinas e or closely related IkappaB kinases is the first cr itical step in NF-kappaB activation. Once phosphorylated, IkappaB is ubiquitinated. Unlike wild-type IkappaBalpha, the phosphorylation-defective mutants do not undergo inducible polyubiquitination. As substitution of a conserved lysine residue slows down the ubiquitination and degradation of IkappaBalpha without affecting its phosphorylation, polyubiquitination is required for inducible IkappaB degradation.

The Relationship of Mutations in the MTHFR, Prothrombin, and PAI-1 Genes to Plasma Levels of Homocysteine, Prothrombin, and PAI-1 in Children and Adults

1999 ◽  
Vol 81 (05) ◽  
pp. 739-744 ◽  
Author(s):  
Vinod Balasa ◽  
Charles Glueck ◽  
Davis Stroop ◽  
Ann Becker ◽  
Ann Pillow ◽  
...  
Keyword(s):  
Plasma Levels ◽  
Methylenetetrahydrofolate Reductase ◽  
Stepwise Multiple Regression ◽  
Similar Data ◽  
Wild Type ◽  
Normal Children ◽  
Increased Risk ◽  
Relationship Of ◽  
The Relationship ◽  
Pai 1

SummaryStudies in adults have demonstrated that the genetic mutations C677T methylenetetrahydrofolate reductase (MTHFR), prothrombin 20210A, and the 4G polymorphism of the plasminogen activator inhibitor-1 (PAI-1) gene are associated with elevated plasma levels of homocysteine, prothrombin and PAI-1, respectively and with an increased risk of thrombosis. No similar data is available in children. Therefore, we assessed the relationship of plasma levels of homocysteine, prothrombin and PAI-1 with their respective mutations in 197 normal children, compared to 40 adults. By stepwise multiple regression, homocysteine was positively associated with age, PAI-1 activity was negatively associated with age, while PAI-1 antigen and prothrombin levels were associated with gender, being higher in girls than boys. When the genotypes were added to the regression model as additional explanatory variables, the MTHFR genotype accounted for 2.9% of the variance of homocysteine (p = 0.024), and the PAI-1 gene accounted for 2.7% of the variance of PAI-1 antigen levels (p = 0.023). Of children homozygous for the MTHFR mutation, 35% had homocysteine levels ≥ the age-specific 95th percentile, compared to 2% hetero-zygotes and 5% wild type normals (p = 0.0001). The mean homocysteine level was higher in children homozygous for the MTHFR gene (8.4 μmol/l) than in heterozygotes (5.5 μmol/l), p <0.05. Of children homozygous for the 4G polymorphism of the PAI-1 gene, 19% had PAI-1 activity levels ≥ the age-specific 95th percentile, compared to 2% of heterozygotes and 3% of wild type normals (p = 0.003). Studies of the incidence of the MTHFR, prothrombin, and PAI-1 4G/5G genotypes in children with thrombosis, when compared to these healthy normals, will provide evidence as to which of these genes are associated with thrombophilia.This work was carried out following an institutional research committee approved protocol with signed informed consent.

scholarly journals PATHOGENIC MECHANISMS OF GENERALIZED PERIODONTITIS FROM THE POSITION OF POLYMORPHISM OF NUCLEAR TRANSCRIPTION FACTOR NF- κВ1

2017 ◽  
Author(s):  
N. V. Hasiuk
Keyword(s):  
Transcription Factor ◽  
Young People ◽  
Periodontal Diseases ◽  
Pathogenic Mechanisms ◽  
Nuclear Transcription Factor ◽  
Polymorphic Gene ◽  
Polymerase Chain ◽  
Relationship Of ◽  
The Relationship ◽  
Determining Factor

Background. Periodontal diseases are a topical issue of contemporary dentistry because they are accompanied by severe morphological and functional disorders of maxillodental system; and are characterized by polyetiology and a number of metabolic disorders.The purpose of this study was to substantiate the pathogenic mechanisms of generalized periodontitis in relation to polymorphism of nuclear transcription factor NF- κB1.Objective. The aim of the study was to determine the genetic factors in the development of generalized periodontitis and the relationship of this parameter with immunohistochemical affiliation for cellular infiltrate of the lamina propria of gum at this nosology in young people. Hence, 2 groups were formed: І – control and II – observational.Methods. Polymorphic gene section NF-κB1 was determined using the cells of buccal epithelium of the examined people by means of polymerase chain reaction. Collection of material was performed with sterile disposable dental brush, followed by the introduction of a reagent in ependorph with DNA Express reagent (LyTeh NPF, Russia). Genome deoxyribonucleic acid was isolated by DNA Express set (LyTeh, Moscow).Results. The lack of correlation in this case indicates that no matter how parameters change, relatively major genotype (Del/Del) in this case is unchanged and the determining factor causes the development of generalized periodontitis, clinical picture of which is rapidly progressing.Conclusions. Results of correlation analysis proved that genotype (Del/Del), as polymorphic variant of gene transcription factor NF-κB1, was significantly associated with the emergence of rapidly progressive periodontitis in young people.

scholarly journals Clinical significance of the BRAFV600E mutation in PTC and its effect on radioiodine therapy

2019 ◽  
Vol 8 (6) ◽  
pp. 754-763 ◽  
Author(s):  
Guoquan Zhu ◽  
Yuying Deng ◽  
Liqin Pan ◽  
Wei Ouyang ◽  
Huijuan Feng ◽  
...  
Keyword(s):  
Radioactive Iodine ◽  
Radioiodine Therapy ◽  
Distant Metastases ◽  
Recurrence Risk ◽  
Capsular Invasion ◽  
Wild Type ◽  
Significant Difference ◽  
Clinicopathologic Factors ◽  
Relationship Of ◽  
The Relationship

The goal of this study was to explore the relationship of the BRAFV600E mutation with clinicopathologic factors and evaluate the effect of radioactive iodine (RAI) therapy in a large group of intermediate- and high-risk papillary thyroid cancer (PTC) patients with the BRAFV600E mutation and without distant metastases. We collected data for PTC patients who underwent total or near-total thyroidectomy and RAI treatment in our hospital from January 2014–December 2017. There were 1220 PTC patients who met the criteria, and the BRAFV600E mutation was observed in 979 of them (80.2%). Multivariate analysis identified that the BRAFV600E mutation remained independently associated with age at diagnosis, and bilaterality (OR = 1.023, 95% CI = 1.012–1.039, P < 0.001; OR = 1.685, 95% CI = 1.213–2.341, P = 0.002, respectively). In addition, the patients with bilateral PTCs had a higher prevalence of extrathyroid invasion, capsular invasion and fusion of metastatic lymph nodes than the unilateral PTC patients. The response to RAI therapy was evaluated in both the entire series and the patients with a high recurrence risk; no significant difference was discerned between the BRAFV600E mutation and the wild-type groups (P = 0.237 and P = 0.498, respectively). To summarize, our results confirmed that PTC patients with the BRAFV600E mutation exhibit more aggressive characteristics. In addition, the patients with bilateral PTC have a higher incidence of extrathyroid invasion. Moreover, BRAFV600E mutation PTC patients did not show a poorer clinical response after postsurgical RAI therapy, suggesting that RAI therapy may improve the general clinical outcome of these patients.

scholarly journals THE RELATIONSHIP OF THIOL STATUS, AND COMPONENTS OF SIGNALING PATHWAYS THAT REGULATE INFLAMMATION IN CONVALESCENTS WITH COMMUNITY-ACQUIRED PNEUMONIA

2018 ◽  
Vol 8 (6) ◽  
pp. 451-457
Author(s):  
S. S. Bondar ◽  
I. V. Terekhov ◽  
V. K. Parfenyuk ◽  
N. V. Bondar ◽  
V. S. Nikiforov
Keyword(s):  
Transcription Factor ◽  
Protein Kinase ◽  
Signaling Pathways ◽  
Mononuclear Cells ◽  
Negative Relationship ◽  
Specific Effect ◽  
Community Acquired Pneumonia ◽  
Nuclear Transcription Factor ◽  
Relationship Of ◽  
The Relationship

The study discusses the relationship of thiol concentrations in intercellular fluid with the level of peripheral blood mononuclear cells (MNCs) in convalescents with community-acquired pneumonia (CAP) components MAPK/SAPK and JAK/STAT-signaling pathways, nuclear transcription factor NF-KB. The content and level of phosphorylation of JAK2 protein kinase, signal transducers and transcription activators STAT3, STAT5A, STAT6, NFKB nuclear transcription factor inhibitor (IkBa), stress-activated protein kinases JNK, ERK, the level of the p50 subunit of nuclear transcription factor NF-κB were determined by enzyme immunoassay in MNC. The results of the study indicate that the stage of reconvalescence of CAP is characterized by a lack of antioxidant protection, manifested by a decrease in the concentration of thiol compounds in the supernatant against which there is a decrease in the level of phosphorylation of protein kinase JAK2, factors STAT3, STAT5, STAT6, JNK, which is also associated with an increase in the level of phosphorylation of protein kinase ERK. The analysis showed that the thiol status is characterized by a positive relationship with the activity of STAT5A, JNK, p50. The level of thiols and ERK, as well as STAT3, was characterized by a negative relationship. Thus, the increase in the level of thiols contributes to the increase in the activity of the transcription factor STAT5A and decrease-STAT3 with a corresponding change in cell reactivity with respect to specific cytokines, as well as a specific effect on the differentiation of individual populations of immunocompetent cells.

scholarly journals Fine-tuning of SUMOylation modulates drought tolerance

2021 ◽  
Author(s):  
Qingmei Guan ◽  
Xuewei Li ◽  
Shuang-Xi Zhou ◽  
Liyuan Lu ◽  
Huan Dang ◽  
...  
Keyword(s):  
Drought Stress ◽  
Drought Tolerance ◽  
Molecular Mechanisms ◽  
Plant Biology ◽  
Fine Tuning ◽  
Wild Type ◽  
Tight Control ◽  
Drought Tolerant ◽  
Relationship Of ◽  
The Relationship

SUMOylation is involved in various aspects of plant biology, including drought stress. However, the relationship between SUMOylation and drought stress tolerance is complex; whether SUMOylation has a crosstalk with ubiquitination in response to drought stress remains largely unclear. In this study, we found that both increased and decreased SUMOylation led to increased survival of apple (Malus × domestica) under drought stress: both transgenic MdSUMO2A overexpressing (OE) plants and MdSUMO2 RNAi plants exhibited enhanced drought tolerance. We further confirmed that MdDREB2A is one of the MdSUMO2 targets. Both transgenic MdDREB2A OE and MdDREB2AK192R OE plants (which lacked the key site of SUMOylation by MdSUMO2A) were more drought tolerant than wild-type plants. However, MdDREB2AK192R OE plants had a much higher survival rate than MdDREB2A OE plants. We further showed SUMOylated MdDREB2A was conjugated with ubiquitin by MdRNF4 under drought stress, thereby triggering its protein degradation. In addition, MdRNF4 RNAi plants were more tolerant to drought stress. These results revealed the molecular mechanisms that underlie the relationship of SUMOylation with drought tolerance and provided evidence for the tight control of MdDREB2A accumulation under drought stress mediated by SUMOylation and ubiquitination.

scholarly journals Inactivation of Transcription Factor Gene ACE2 in the Fungal Pathogen Candida glabrata Results in Hypervirulence

2004 ◽  
Vol 3 (2) ◽  
pp. 546-552 ◽  
Author(s):  
Mohammed Kamran ◽  
Ana-Maria Calcagno ◽  
Helen Findon ◽  
Elaine Bignell ◽  
Michael D. Jones ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Candida Glabrata ◽  
Critical Role ◽  
Innate Immune ◽  
Clear Understanding ◽  
Wild Type ◽  
Transcription Factor Gene ◽  
Factor Gene ◽  
Systemic Infections

ABSTRACT During an infection, the coordinated orchestration of many factors by the invading organism is required for disease to be initiated and to progress. The elucidation of the processes involved is critical to the development of a clear understanding of host-pathogen interactions. For Candida species, the inactivation of many fungal attributes has been shown to result in attenuation. Here we demonstrate that the Candida glabrata homolog of the Saccharomyces cerevisiae transcription factor gene ACE2 encodes a function that mediates virulence in a novel way. Inactivation of C. glabrata ACE2 does not result in attenuation but, conversely, in a strain that is hypervirulent in a murine model of invasive candidiasis. C. glabrata ace2 null mutants cause systemic infections characterized by fungal escape from the vasculature, tissue penetration, proliferation in vivo, and considerable overstimulation of the proinflammatory arm of the innate immune response. Compared to the case with wild-type fungi, mortality occurs much earlier in mice infected with C. glabrata ace2 cells, and furthermore, 200-fold lower doses are required to induce uniformly fatal infections. These data demonstrate that C. glabrata ACE2 encodes a function that plays a critical role in mediating the host-Candida interaction. It is the first virulence-moderating gene to be described for a Candida species.

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