The role of symmetry in the regulation of bacterial carboxyltransferase

2011 ◽  
Vol 2 (1-2) ◽  
pp. 47-52 ◽  
Author(s):  
Grover L. Waldrop
Keyword(s):  
Gene Expression ◽  
Enzymatic Activity ◽  
Chemical Reaction ◽  
Binding Sites ◽  
Fatty Acid Biosynthesis ◽  
Acid Biosynthesis ◽  
Effective Mechanism ◽  
Acetyl Coa ◽  
Mrna Binding

AbstractCarboxyltransferase is one component of the multifunctional enzyme acetyl-CoA carboxylase which catalyzes the first committed step in fatty acid biosynthesis. Carboxyltransferase is an α2β2heterotetramer and possesses two distinct but integrated functions. One function catalyzes the transfer of carbon dioxide from biotin to acetyl-CoA, whereas the other involves binding to the mRNA encoding both subunits. When carboxyltransferase binds to the mRNA both enzymatic activity and translation of the mRNA are inhibited. However, the substrate acetyl-CoA competes with mRNA for binding. Thus, mRNA binding by carboxyltransferase provides an effective mechanism for regulating enzymatic activity and gene expression. This conceptual review takes the position that regulation of enzymatic activity and gene expression of carboxyltransferase by binding to its own mRNA is at its most fundamental level the result of the symmetry in the chemical reaction catalyzed by the enzyme. The chemical reaction is symmetrical in that both substrates generate enolate anions during the course of catalysis. The chemical symmetry led to a structural symmetry in the enzyme where both the α and β subunits contain oxyanion holes that stabilize the enolate anions. Then the region of the mRNA that codes for the oxyanion holes provided the binding sites for carboxyltransferase. Thus, the symmetry of the chemical reaction formed the foundation for the evolution of the mechanism for regulation of carboxyltransferase.

The role of phosphorylation/dephosphorylation of acetyl-CoA carboxylase in the regulation of mammalian fatty acid biosynthesis

1986 ◽  
Vol 14 (3) ◽  
pp. 559-562 ◽  
Author(s):  
MICHAEL R. MUNDAY ◽  
TIMOTHY A. J. HAYSTEAD ◽  
ROSS HOLLAND ◽  
DAVID A. CARLING ◽  
D. GRAHAME HARDIE
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Biosynthesis ◽  
Acetyl Coa Carboxylase ◽  
Acid Biosynthesis ◽  
Acetyl Coa

scholarly journals Trans-activation of the human SOX3 promoter by MAZ in NT2/D1 cells

2008 ◽  
Vol 60 (3) ◽  
pp. 379-387 ◽  
Author(s):  
Natasa Kovacevic-Grujicic ◽  
Kazunari Yokoyama ◽  
Milena Stevanovic
Keyword(s):  
Gene Expression ◽  
Neuronal Differentiation ◽  
Gene Transcription ◽  
Binding Sites ◽  
Promoter Activity ◽  
Zinc Finger Protein ◽  
Mobility Shift ◽  
Finger Protein ◽  
Sox3 Gene

In this study, we examine the role of three highly conserved putative binding sites for Myc-associated zinc finger protein (MAZ) in regulation of the human SOX3 gene expression. Electrophoretic mobility shift and supershift assays indicate that complexes formed at two out of three MAZ sites of the human SOX3 promoter involve ubiquitously expressed MAZ protein. Furthermore, in cotransfection experiments we demonstrate that MAZ acts as a positive regulator of SOX3 gene transcription in both undifferentiated and RA-differentiated NT2/D1 cells. Although MAZ increased both basal and RA-induced promoter activity, our results suggest that MAZ does not contribute to RA inducibility of the SOX3 promoter during neuronal differentiation of NT2/D1 cells.

Abstract MP204: Pyruvate Dehydrogenase Kinase Isozyme Specific Regulation Of Protein Acetylation In Cardiac Tissue

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Chae-Myeong Ha ◽  
Adam R Wende
Keyword(s):  
Gene Expression ◽  
Heart Disease ◽  
Knockout Mice ◽  
Pyruvate Dehydrogenase ◽  
Cardiac Tissue ◽  
Cell Protein ◽  
Protein Acetylation ◽  
Acetyl Coa ◽  
The Impact

Heart disease is the number one cause of death in developed countries. Metabolic diseases influence the severity of heart disease linked to risk factors which are thought to alter epigenetic mechanisms. Pyruvate dehydrogenase (PDH) kinases (PDK), which phosphorylate and reduce the activity of PDH the nexus of glucose oxidation and fatty acid oxidation are sensitive to metabolic status. Four isozymes of PDK (PDK1-4) exist with PDK2 and PDK4 as the major regulators in cardiac tissue. Owing to the role of PDH in regulating pyruvate to acetyl-CoA, we hypothesized that PDK inhibition may regulate protein acetylation through increasing acetyl-CoA because of PDH activation leading to post-translational modifications both directly to proteins in metabolic pathways as well as to histones associated with the genes encoding them. To test this, we utilized PDK2 germline knockout mice (P2KO), PDK4 germline knockout mice (P4KO), and PDK2 and PDK4 double knockout (DKO) mice for molecular analysis. Our results identify a novel increase in whole-cell protein acetylation in P2KO left ventricle tissue (LV). However, protein acetylation in P4KO LV was not changed compared to WT mice. The most robust protein acetylation was observed in the DKO LV. Furthermore, when we explored sub-cellular distribution of protein acetylation, the greatest increases were found on cytoplasmic proteins, with moderate changes in mitochondrial proteins. We also found PDK2 ablation induces histone H3 acetylation, which may also lead to changes in gene expression. Moreover, this protein acetylation in P2KO and DKO was not seen in other tissues examined (e.g., liver, skeletal muscle). The hyperacetylation is robust in male LV compared to female LV. In conclusion, our study supports a novel protein acetylation mechanism that is both tissue and PDK isozyme specific highlighting the role of PDK2, which is relatively understudied compared to PDK4 in heart disease. Further study will evaluate if the hyperacetylation has a beneficial effect in various heart disease settings as well as identify the impact on changes in gene expression. This study supports PDK isozyme-specific inhibition strategies will be required to develop therapeutic targets of cardiovascular disease with metabolic inflexibility.

The role of β-ketoacyl-acyl carrier protein synthase III in the condensation steps of fatty acid biosynthesis in sunflower

Planta ◽  
2010 ◽  
Vol 231 (6) ◽  
pp. 1277-1289 ◽  
Author(s):  
Damián González-Mellado ◽  
Penny von Wettstein-Knowles ◽  
Rafael Garcés ◽  
Enrique Martínez-Force
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Biosynthesis ◽  
Acyl Carrier Protein ◽  
Carrier Protein ◽  
Acid Biosynthesis

scholarly journals Direct and widespread role for the nuclear receptor EcR in mediating the response to ecdysone in Drosophila

2019 ◽  
Vol 116 (20) ◽  
pp. 9893-9902 ◽  
Author(s):  
Christopher M. Uyehara ◽  
Daniel J. McKay
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Nuclear Receptor ◽  
Binding Sites ◽  
Transcriptional Responses ◽  
Enhancer Activity ◽  
Developmental Transitions ◽  
Experimental Systems ◽  
The Impact

The ecdysone pathway was among the first experimental systems employed to study the impact of steroid hormones on the genome. In Drosophila and other insects, ecdysone coordinates developmental transitions, including wholesale transformation of the larva into the adult during metamorphosis. Like other hormones, ecdysone controls gene expression through a nuclear receptor, which functions as a ligand-dependent transcription factor. Although it is clear that ecdysone elicits distinct transcriptional responses within its different target tissues, the role of its receptor, EcR, in regulating target gene expression is incompletely understood. In particular, EcR initiates a cascade of transcription factor expression in response to ecdysone, making it unclear which ecdysone-responsive genes are direct EcR targets. Here, we use the larval-to-prepupal transition of developing wings to examine the role of EcR in gene regulation. Genome-wide DNA binding profiles reveal that EcR exhibits widespread binding across the genome, including at many canonical ecdysone response genes. However, the majority of its binding sites reside at genes with wing-specific functions. We also find that EcR binding is temporally dynamic, with thousands of binding sites changing over time. RNA-seq reveals that EcR acts as both a temporal gate to block precocious entry to the next developmental stage as well as a temporal trigger to promote the subsequent program. Finally, transgenic reporter analysis indicates that EcR regulates not only temporal changes in target enhancer activity but also spatial patterns. Together, these studies define EcR as a multipurpose, direct regulator of gene expression, greatly expanding its role in coordinating developmental transitions.

The possible role of BnaA10.SOI.a in seed fatty acid biosynthesis of rapeseed

2019 ◽  
Vol 139 (1) ◽  
pp. 167-175
Author(s):  
Jingyun Gong ◽  
Dong Li ◽  
Xinye Li ◽  
Xuchen Yu ◽  
Yuan Guo ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Biosynthesis ◽  
Acid Biosynthesis ◽  
Seed Fatty Acid

Effect of Thiolactomycin on de novo Fatty Acid Biosynthesis in Plants

1990 ◽  
Vol 45 (5) ◽  
pp. 518-520 ◽  
Author(s):  
Manfred Focke ◽  
Andrea Feld ◽  
Hartmut K. Lichtenthaler
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Biosynthesis ◽  
De Novo ◽  
Fatty Acid Synthetase ◽  
Acetate Incorporation ◽  
Acid Biosynthesis ◽  
Acetyl Coa ◽  
Malonyl Coa ◽  
Total Fatty Acids

Thiolactomycin was shown to be a potent inhibitor of de novo fatty acid biosynthesis in intact isolated chloroplasts (measured as [14C]acetate incorporation into total fatty acids). In our attempt to further localize the inhibition site we confirmed the inhibition with a fatty acid synthetase preparation, measuring the incorporation of [14C]malonyl-CoA into total fatty acids. From the two proposed enzymic targets of the fatty acid synthetase by thiolactomycin we could exclude the acetyl-CoA: ACP transacetylase. It appears that the inhibition by thiolactomycin occurs on the level of the condensing enzymes, i.e. the 3-oxoacyl-ACP synthases. We also demonstrated that the two starting enzymes of de novo fatty acid biosynthesis, the acetyl-CoA synthetase and the acetyl-CoA carboxylase, are not affected by thiolactomycin.

scholarly journals Pituitary transcription factor Prop-1 stimulates porcine pituitary glycoprotein hormone α subunit gene expression

2006 ◽  
Vol 37 (2) ◽  
pp. 341-352 ◽  
Author(s):  
Takanobu Sato ◽  
Kousuke Kitahara ◽  
Takao Susa ◽  
Takako Kato ◽  
Yukio Kato
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Binding Sites ◽  
Gh3 Cells ◽  
Pituitary Hormone ◽  
Transcriptional Level ◽  
Β Subunit ◽  
Glycoprotein Hormone ◽  
Α Subunit

Recently, we have reported that a Prophet of Pit-1 homeodomain factor, Prop-1, is a novel transcription factor for the porcine follicle-stimulating hormone β subunit (FSHβ) gene. This study subsequently aimed to examine the role of Prop-1 in the gene expression of two other porcine gonadotropin subunits, pituitary glycoprotein hormone α subunit (αGSU), and luteinizing hormone β subunit (LHβ). A series of deletion mutants of the porcine αGSU (up to −1059 bp) and LHβ (up to −1277 bp) promoters were constructed in the reporter vector, fused with the secreted alkaline phosphatase gene (pSEAP2-Basic). Transient transfection studies using GH3 cells were carried out to estimate the activation of the porcine αGSU and LHβ promoters by Prop-1, which was found to activate the αGSU promoter of −1059/+12 bp up to 11.7-fold but not the LHβ promoter. Electrophoretic mobility shift assay and DNase I footprinting analysis revealed that Prop-1 binds to six positions, −1038/−1026, −942/−928, −495/−479, −338/−326, −153/−146, and −131/−124 bp, that comprise the A/T cluster. Oligonucleotides of six Prop-1 binding sites were directly connected to the minimum promoter of αGSU, fused in the pSEAP2-Basic vector, followed by transfecting GH3 cells to determine the cis-acting activity. Finally, we concluded that at least five Prop-1 binding sites are the cis-acting elements for αGSU gene expression. The present results revealed a notable feature of the proximal region, where three Prop-1-binding sites are close to and/or overlap the pituitary glycoprotein hormone basal element, GATA-binding element, and junctional regulatory element. To our knowledge, this is the first demonstration of the role of Prop-1 in the regulation of αGSU gene expression. These results, taken together with our previous finding that Prop-1 is a transcription factor for FSHβ gene, confirm that Prop-1 modulates the synthesis of FSH at the transcriptional level. On the other hand, the defects of Prop-1 are known to cause dwarfism and combined pituitary hormone deficiency accompanying hypogonadism. Accordingly, the present observations provide a novel view to understand the hypogonadism caused by Prop-1 defects at the molecular level through the regulatory mechanism of αGSU and FSHβ gene expressions.

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