Gene expression in Drosophila: Post-translational modification of aldehyde oxidase and xanthine dehydrogenase

1979 ◽  
Vol 172 (1) ◽  
pp. 37-43 ◽  
Author(s):  
Victoria Finnerty ◽  
Margaret McCarron ◽  
George B. Johnson
Keyword(s):  
Gene Expression ◽  
Aldehyde Oxidase ◽  
Xanthine Dehydrogenase ◽  
Post Translational Modification

scholarly journals POST-TRANSLATIONAL MODIFICATION OF XANTHINE DEHYDROGENASE IN A NATURAL POPULATION OF DROSOPHILA MELANOGASTER

Genetics ◽  
1981 ◽  
Vol 98 (4) ◽  
pp. 817-831
Author(s):  
George Johnson ◽  
Victoria Finnerty ◽  
Daniel Hartl
Keyword(s):  
Drosophila Melanogaster ◽  
Natural Population ◽  
Aldehyde Oxidase ◽  
Xanthine Dehydrogenase ◽  
Chromosome 3 ◽  
Chromosome 2 ◽  
Structural Genes ◽  
Post Translational Modification ◽  
Polymorphic Loci

ABSTRACT Second chromosomes of D. melanogaster were isolated from a single natural population, and 40 were analyzed by gel-sieving electrophoresis for the presence of polymorphic loci on chromosome 2 that act to modify xanthine dehydrogenase and/or aldehyde oxidase, whose structural genes map to chromosome 3. Clear evidence of polymorphism for one or more xanthine dehydrogenase modifier loci was obtained.

scholarly journals POST-TRANSLATIONAL MODIFICATION AS A POTENTIAL EXPLANATION OF HIGH LEVELS OF ENZYME POLYMORPHISM: XANTHINE DEHYDROGENASE AND ALDEHYDE OXIDASE IN DROSOPHILA MELANOGASTER

Genetics ◽  
1979 ◽  
Vol 91 (4) ◽  
pp. 695-722
Author(s):  
Victoria Finnerty ◽  
George Johnson
Keyword(s):  
Drosophila Melanogaster ◽  
Natural Populations ◽  
Aldehyde Oxidase ◽  
Xanthine Dehydrogenase ◽  
Enzyme Polymorphism ◽  
The Body ◽  
Post Translational Modification ◽  
Heritable Variation ◽  
Thermal Stabilities ◽  
Partial Restoration

ABSTRACT Xanthine dehydrogenase (XDH) and aldehyde oxidase (AO) in Drosophila melanogaster require for their activity the action of another unlinked locus, maroon-like (mal), While the XDH and A 0 loci are on chromosome 3, mal maps to the X chromosome. Although functional mal gene product is required for XDH and A 0 activity, it is possible to examine the effects of mutant mal alleles in those cases when pairs of mutants complement to produce a partial restoration of activity. To test whether mal mediates a post-translational modification of the XDH and A0 proteins, we constructed several mal heteroallelic complementing stocks of Drosophila in which the third chromosomes were co-isogenic. Since all lines were co-isogenic for the XDH and A0 structural genes, any variation in these enzymes seen when comparing these stocks must have been produced by post-translational modification by mal. We examined the XDH and A 0 proteins in these stocks by gel-sieving electrophoresis, a procedure that permits independent characterization of a protein's charge and shape, and is capable of discriminating many variants not detected in routine electrophoresis. In every mal heteroallelic combination, there is a significant alteration in protein shape, when compared to wild type. The magnitude of differences in shape of XDH and AO is correlated both with differences in their enzyme activities and with differences in their thermal stabilities. As the body of this variation appears heritable, any functional differences resulting from these variants are of real genetic and evolutionary interest. A similar post-translational modification of XDH and A0 by yet another locus, lxd, was subsequently documented in an analogous manner. The pattern of electrophoretic differences produced by mal and lxd modification is similar to that reported for electrophoretic "alleles" of XDH in natural populations. The implication is that heritable variation in electrophoretic mobility at these two enzyme loci, and potentially at other loci, is not necessarily allelic to the structural gene loci.

Review of Progress in Predicting Protein Methylation Sites

2019 ◽  
Vol 23 (15) ◽  
pp. 1663-1670 ◽  
Author(s):  
Chunyan Ao ◽  
Shunshan Jin ◽  
Yuan Lin ◽  
Quan Zou
Keyword(s):  
Gene Expression ◽  
Signal Transduction ◽  
Transcriptional Activity ◽  
Regulation Of Gene Expression ◽  
Protein Methylation ◽  
Biological Processes ◽  
Post Translational Modification ◽  
Regulatory Enzymes ◽  
Lysine Residues ◽  
Arginine Residues

Protein methylation is an important and reversible post-translational modification that regulates many biological processes in cells. It occurs mainly on lysine and arginine residues and involves many important biological processes, including transcriptional activity, signal transduction, and the regulation of gene expression. Protein methylation and its regulatory enzymes are related to a variety of human diseases, so improved identification of methylation sites is useful for designing drugs for a variety of related diseases. In this review, we systematically summarize and analyze the tools used for the prediction of protein methylation sites on arginine and lysine residues over the last decade.

scholarly journals Androgen signaling uses a writer and a reader of ADP-ribosylation to regulate protein complex assembly

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Chun-Song Yang ◽  
Kasey Jividen ◽  
Teddy Kamata ◽  
Natalia Dworak ◽  
Luke Oostdyk ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Interactions ◽  
Prostate Cancer Cells ◽  
Protein Protein Interactions ◽  
Post Translational Modification ◽  
Complex Assembly ◽  
Adp Ribosylation ◽  
Signaling Axis ◽  
Regulate Protein ◽  
Protein Complex Assembly

AbstractAndrogen signaling through the androgen receptor (AR) directs gene expression in both normal and prostate cancer cells. Androgen regulates multiple aspects of the AR life cycle, including its localization and post-translational modification, but understanding how modifications are read and integrated with AR activity has been difficult. Here, we show that ADP-ribosylation regulates AR through a nuclear pathway mediated by Parp7. We show that Parp7 mono-ADP-ribosylates agonist-bound AR, and that ADP-ribosyl-cysteines within the N-terminal domain mediate recruitment of the E3 ligase Dtx3L/Parp9. Molecular recognition of ADP-ribosyl-cysteine is provided by tandem macrodomains in Parp9, and Dtx3L/Parp9 modulates expression of a subset of AR-regulated genes. Parp7, ADP-ribosylation of AR, and AR-Dtx3L/Parp9 complex assembly are inhibited by Olaparib, a compound used clinically to inhibit poly-ADP-ribosyltransferases Parp1/2. Our study reveals the components of an androgen signaling axis that uses a writer and reader of ADP-ribosylation to regulate protein-protein interactions and AR activity.

scholarly journals Identification of a new mutation in the human xanthine dehydrogenase responsible for xanthinuria type I

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Cristina Collazo Abal ◽  
Susana Romero Santos ◽  
Carmen González Mao ◽  
Emilio C. Pazos Lago ◽  
Francisco Barros Angueira ◽  
...  
Keyword(s):  
Aldehyde Oxidase ◽  
Renal Calculi ◽  
Xanthine Dehydrogenase ◽  
Type I ◽  
Dietary Recommendations ◽  
New Mutation ◽  
Case Presentation ◽  
Hereditary Xanthinuria ◽  
Urine Levels ◽  
Made In

Abstract Objectives Hereditary xanthinuria is a rare, autosomal and recessive disorder characterized by severe hypouricemia and increased xanthine excretion, caused by a deficiency of xanthine dehydrogenase/oxidase (XDH/XO, EC: 1.17.1.4/1.17.3.2) in type I, or by a deficiency of XDH/XO and aldehyde oxidase (AOX, EC: 1.2.3.1) in type II. Case presentation We describe a novel point mutation in the XDH gene in homozygosis found in a patient with very low serum and urine levels of uric acid, together with xanthinuria. He was asymptomatic but renal calculi were discovered during imaging. Additional cases were found in his family and dietary recommendations were made in order to prevent further complications. Conclusions Hereditary xanthinuria is an underdiagnosed pathology, often found in a routine analysis that shows hypouricemia. It is important for Laboratory Medicine to acknowledge how to guide clinicians in the diagnosis.

scholarly journals O-GlcNAc regulates gene expression by controlling detained intron splicing

2020 ◽  
Vol 48 (10) ◽  
pp. 5656-5669 ◽  
Author(s):  
Zhi-Wei Tan ◽  
George Fei ◽  
Joao A Paulo ◽  
Stanislav Bellaousov ◽  
Sara E S Martin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Intron Splicing ◽  
Post Translational Modification ◽  
Substantial Fraction ◽  
Control Gene Expression ◽  
Almost All ◽  
Glcnac Transferase ◽  
Eukaryotic Genomes ◽  
Specific Inhibitors ◽  
Nutrient Conditions

Abstract Intron detention in precursor RNAs serves to regulate expression of a substantial fraction of genes in eukaryotic genomes. How detained intron (DI) splicing is controlled is poorly understood. Here, we show that a ubiquitous post-translational modification called O-GlcNAc, which is thought to integrate signaling pathways as nutrient conditions fluctuate, controls detained intron splicing. Using specific inhibitors of the enzyme that installs O-GlcNAc (O-GlcNAc transferase, or OGT) and the enzyme that removes O-GlcNAc (O-GlcNAcase, or OGA), we first show that O-GlcNAc regulates splicing of the highly conserved detained introns in OGT and OGA to control mRNA abundance in order to buffer O-GlcNAc changes. We show that OGT and OGA represent two distinct paradigms for how DI splicing can control gene expression. We also show that when DI splicing of the O-GlcNAc-cycling genes fails to restore O-GlcNAc homeostasis, there is a global change in detained intron levels. Strikingly, almost all detained introns are spliced more efficiently when O-GlcNAc levels are low, yet other alternative splicing pathways change minimally. Our results demonstrate that O-GlcNAc controls detained intron splicing to tune system-wide gene expression, providing a means to couple nutrient conditions to the cell's transcriptional regime.

Constitutive Activation of SHP2 Protein Tyrosine Phosphatase Cooperates with HoxA10 Overexpression for Progression to Acute Myeloid Leukemia in a Murine Model

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 752-752
Author(s):  
Hao Wang ◽  
Stephan Lindsey ◽  
Iwona Konieczna ◽  
Elizabeth Horvath ◽  
Ling Bei ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Protein Tyrosine Phosphatase ◽  
Myeloid Leukemia ◽  
Tyrosine Phosphatase ◽  
Post Translational Modification ◽  
Protein Tyrosine ◽  
Acute Myeloid ◽  
Myeloid Progenitors

Abstract HOX genes encode highly conserved homeodomain (HD) transcription factors and are arranged in four groups (A–D). During definitive hematopoiesis, HOX gene expression is activated 3′ to 5′ through each group. Therefore, HOX1-4 are actively transcribed in hematopoietic stem cells and HOX7-11 in committed progenitors. Under normal conditions, HoxA7-11 expression decreases during CD34+ to CD34− maturation. Abnormal Hox expression is characteristic of several poor prognosis subtypes of Acute Myeloid Leukemia (AML) including AML with translocations or duplications of the MLL gene. In such leukemias, expression of HoxB3, B4 and A7-11 is sustained in CD34−CD38+ cells. In murine bone marrow transplantation experiments, expression of MLL fusion proteins, HoxA9 or HoxA10 induces a myeloproliferative disorder (MPD) characterized by increased neutrophils (PMN). Over time, the mice progress to AML with circulating myeloid blasts. These results suggest overexpression of HoxA9 or HoxA10 is adequate for MPD, but differentiation block (AML) requires additional lesions. We found that HoxA9 and HoxA10 proteins not only decrease in expression during the CD34+ to CD34− transition, but also are tyrosine phosphorylated. In additional studies, we found that HoxA10 tyrosine phosphorylation state is relevant for differentiation stage-specific target gene expression during myelopoiesis. HoxA10 represses genes encoding phagocyte effector proteins in undifferentiated myeloid cells. During myelopoiesis, phosphorylation of conserved HD-HoxA10 tyrosines decreases binding to these genes, permitting phenotypic and functional differentiation. HoxA10 activates transcription of the gene encoding Mkp2 (Dusp4) in myeloid progenitors. Decrease in HoxA10-binding to this gene as differentiation proceeds decreases transcription and renders the cells susceptible to Jnk induced apoptosis. Therefore, we hypothesized that genetic lesions which influence post translational modification might cooperate with HoxA10 overexpression to lead from MPD to AML. In myeloid progenitors, HoxA10 is maintained in a non-phosphorylated state by SHP2 protein tyrosine phosphatase. SHP2 activity decreases as differentiation proceeds. Activating mutations in SHP2 have been described in AML. We found that such activated SHP2 mutants dephosphorylate HoxA10 through out ex vivo myelopoiesis. Therefore, we investigated cooperation between these two leukemia associated abnormalities in vivo. Mice were transplanted with bone marrow overexpressing HoxA10 (or empty vector control) with or without activated SHP2 (E76K). To control for SHP2 overexpression, other mice were transplanted with bone marrow overexpressing HoxA10 and wild type SHP2. Mice transplanted with bone marrow overexpressing HoxA10 (±SHP2) developed MPD which evolved to AML over 4 mos, consistent with previous observations. However, mice transplanted with bone marrow overexpressing HoxA10 and E76K SHP2 developed AML within 4 wks. This rapid development of AML correlated with abnormalities in expression of myeloid specific HoxA10 target genes. These studies indicate the importance of HoxA10 post translational modification for physiologically relevant function and identify cooperating lesions which may be significant for disease progression in human AML.

Expression Profile and up-Regulation of Telomere-Associated Proteins In Multiple Myeloma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4050-4050
Author(s):  
Rafael Díaz de la Guardia ◽  
Carolina Elosua ◽  
Purificación Catalina ◽  
Brian A Walker ◽  
David C Johnson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Telomere Length ◽  
Conflicts Of Interest ◽  
Telomerase Activity ◽  
Telomere Maintenance ◽  
Post Translational Modification ◽  
Human Telomerase Reverse Transcriptase ◽  
Immortal Cells ◽  
Human Telomerase

Abstract Abstract 4050 The role of the telomeres in the mechanisms of ageing and carcinogenesis has generated a considerable interest as a novel approach to the treatment of many cancers. Telomeres are nucleoproteins structures that protect the ends of eukaryotic chromosomes, which are particularly vulnerable due to progressive shortening in almost all dividing cells. The telomere length was observed as a critical factor in the initiation and progression of human cancers, and it is associated to chromosomal instability. Most immortal cells possess enzymatic activity of telomerase. This suggests that telomerase activity and telomere length maintenance may be required for unlimited cell proliferation, tumorigenesis, and protection, allowing the evasion of apoptosis in cancer development. The telomerase activity could also be regulated positively or negatively by post-trancriptional and/or post-translational modification of the enzyme without transcriptional up-regulation of human telomerase reverse transcriptase (hTERT) mRNA. In this work, we analyze the expression data of all genes involved in telomerase activity. Patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), multiple myeloma (MM) and plasma cell leukemia (PLC) were studied through gene expression profiling analysis (Human Genome U133 Plus 2.0 arrays, Affymetrix). We identify 21 deregulated genes, implicated directly in telomere length maintenance activity in clonal plasma cells compared with normal cells (20 up-regulated and 1 down-regulated). These genes are MYC, KRAS, HSPA9, RB1 and members of the families: Small nucleolar ribonucleoproteins (H/ACA snoRNPs), A/B subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs), and 14-3 -3 family. In conclusion, the myeloma cells acquire the telomere maintenance capability without deregulation of the human telomerase RNA gene (hTERC) and hTERT gene expression. It is an alternative lengthening of telomeres mechanism that has effect in the regulation of the BAD activity in apoptosis. The mechanism is based on preventing the partially-denatured proteins from aggregating, telomere maintenance through the correct processing and intranuclear trafficking of hTERC, telomerase reactivation and telomere stabilization, and efficient accumulation of hTERT in the nucleus. Thus, the findings of this study may help to improve telomerase-based therapy for multiple myeloma. Disclosures: No relevant conflicts of interest to declare.

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