Browse
Submit Data
Databases
API
Help

Dataset Information

9 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Chloramphenicol inhibits eukaryotic Ser/Thr phosphatase and infection-specific cell differentiation in the rice blast fungus.

ABSTRACT: Chloramphenicol (Cm) is a broad-spectrum classic antibiotic active against prokaryotic organisms. However, Cm has severe side effects in eukaryotes of which the cause remains unknown. The plant pathogenic fungus Magnaporthe oryzae, which causes rice blast, forms an appressorium to infect the host cell via single-cell differentiation. Chloramphenicol specifically inhibits appressorium formation, which indicates that Cm has a novel molecular target (or targets) in the rice blast fungus. Application of the T7 phage display method inferred that MoDullard, a Ser/Thr-protein phosphatase, may be a target of Cm. In animals Dullard functions in cell differentiation and protein synthesis, but in fungi its role is poorly understood. In vivo and in vitro analyses showed that MoDullard is required for appressorium formation, and that Cm can bind to and inhibit MoDullard function. Given that human phosphatase CTDSP1 complemented the MoDullard function during appressorium formation by M. oryzae, CTDSP1 may be a novel molecular target of Cm in eukaryotes.

SUBMITTER: Nozaka A

PROVIDER: S-EPMC6594944 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Phosphorylation of Mycobacterium tuberculosis Ser/Thr phosphatase by PknA and PknB.

Project description:The integrated functions of 11 Ser/Thr protein kinases (STPKs) and one phosphatase manipulate the phosphorylation levels of critical proteins in Mycobacterium tuberculosis. In this study, we show that the lone Ser/Thr phosphatase (PstP) is regulated through phosphorylation by STPKs.PstP is phosphorylated by PknA and PknB and phosphorylation is influenced by the presence of Zn(2+)-ions and inorganic phosphate (Pi). PstP is differentially phosphorylated on the cytosolic domain with Thr(137), Thr(141), Thr(174) and Thr(290) being the target residues of PknB while Thr(137) and Thr(174) are phosphorylated by PknA. The Mn(2+)-ion binding residues Asp(38) and Asp(229) are critical for the optimal activity of PstP and substitution of these residues affects its phosphorylation status. Native PstP and its phosphatase deficient mutant PstP(c) (D38G) are phosphorylated by PknA and PknB in E. coli and addition of Zn(2+)/Pi in the culture conditions affect the phosphorylation level of PstP. Interestingly, the phosphorylated phosphatase is more active than its unphosphorylated equivalent.This study establishes the novel mechanisms for regulation of mycobacterial Ser/Thr phosphatase. The results indicate that STPKs and PstP may regulate the signaling through mutually dependent mechanisms. Consequently, PstP phosphorylation may play a critical role in regulating its own activity. Since, the equilibrium between phosphorylated and non-phosphorylated states of mycobacterial proteins is still unexplained, understanding the regulation of PstP may help in deciphering the signal transduction pathways mediated by STPKs and the reversibility of the phenomena.

| S-EPMC3052367 | biostudies-literature

Marine Longilenes, Oxasqualenoids with Ser-Thr Protein Phosphatase 2A Inhibition Activity.

Project description:The red seaweed Laurencia viridis is a rich source of oxygenated secondary metabolites that were derived from squalene. We report here the structures of three novel compounds, (+)-longilene peroxide (1), longilene (2), and (+)-prelongilene (3) that were isolated from this alga, in addition to other substances, 4 and 5, resulting from their acid-mediated degradation. The effect of compounds 1 and 3 against Ser-Thr protein phosphatase type 2A (PP2A) was evaluated, showing that (+)-longilene peroxide (1) inhibited PP2A (IC50 11.3 μM). In order to explain the interaction between PP2A and compounds 1 and 3, molecular docking simulations onto the PP2A enzyme-binding region were used.

| S-EPMC5923418 | biostudies-literature

Transcriptome analysis of the eukaryotic-type ser/thr kinase PknB in Staphylococcus aureus

2010-03-11 | GSE15346 | GEO

Transcriptome analysis of the eukaryotic-type ser/thr kinase PknB in Staphylococcus aureus

Project description:The function of the Staphylococcus aureus eukaryotic-like serine/threonine protein kinase PknB was investigated by transcriptome analysis using DNA-microarray technology and biochemical assays. The transcriptional profile reveals a strong regulatory impact of PknB on the expression of genes encoding proteins which are involved in purine and pyrimidine biosynthesis, cell wall metabolism, autolysis, and glutamine synthesis. To investigate the functional role of PknB in S. aureus DNA microarray experiments were performed. In this experiment, the impact of the deletion of PknB was investigated. Each experiment was performed 5 times including a dye swap resulting in five chips per competitive comparison to increase reproducibility. All hybridizations were done with equal amounts of cDNA probes.

2010-05-05 | E-GEOD-15346 | biostudies-arrayexpress

Optimization of a cyclic peptide inhibitor of Ser/Thr phosphatase PPM1D (Wip1).

Project description:PPM1D (PP2Cδ or Wip1) was identified as a wild-type p53-induced Ser/Thr phosphatase that accumulates after DNA damage and classified into the PP2C family. It dephosphorylates and inactivates several proteins critical for cellular stress responses, including p38 MAPK, p53, and ATM. Furthermore, PPM1D is amplified and/or overexpressed in a number of human cancers. Thus, inhibition of its activity could constitute an important new strategy for therapeutic intervention to halt the progression of several different cancers. Previously, we reported the development of a cyclic thioether peptide with low micromolar inhibitory activity toward PPM1D. Here, we describe important improvements in the inhibitory activity of this class of cyclic peptides and also present a binding model based upon the results. We found that specific interaction of an aromatic ring at the X1 position and negative charge at the X5 and X6 positions significantly increased the inhibitory activity of the cyclic peptide, with the optimized molecule having a K(i) of 110 nM. To the best of our knowledge, this represents the highest inhibitory activity reported for an inhibitor of PPM1D. We further developed an inhibitor selective for PPM1D over PPM1A with a K(i) of 2.9 μM. Optimization of the cyclic peptide and mutagenesis experiments suggest that a highly basic loop unique to PPM1D is related to substrate specificity. We propose a new model for the catalytic site of PPM1D and inhibition by the cyclic peptides that will be useful both for the subsequent design of PPM1D inhibitors and for identification of new substrates.

| S-EPMC3508689 | biostudies-literature

Chitin-deacetylase activity induces appressorium differentiation in the rice blast fungus Magnaporthe oryzae.

Project description:The rice blast fungus Magnaporthe oryzae differentiates a specialized infection structure called an appressorium to invade rice cells. In this report, we show that CBP1, which encodes a chitin-deacetylase, is involved in the induction phase of appressorium differentiation. We demonstrate that the enzymatic activity of Cbp1 is critical for appressorium formation. M. oryzae has six CDA homologues in addition to Cbp1, but none of these are indispensable for appressorium formation. We observed chitosan localization at the fungal cell wall using OGA488. This observation suggests that Cbp1-catalysed conversion of chitin into chitosan occurs at the cell wall of germ tubes during appressorium differentiation by M. oryzae. Taken together, our results provide evidence that the chitin deacetylase activity of Cbp1 is necessary for appressorium formation.

| S-EPMC5575296 | biostudies-literature

Extremely Low Concentrations of Acetic Acid Stimulate Cell Differentiation in Rice Blast Fungus.

Project description:Metabolic switching and rewiring play a dynamic role in programmed cell differentiation. Many pathogenic microbes need to survive in nutrient-deficient conditions and use the glyoxylate cycle, an anaplerotic pathway of the tricarboxylic acid cycle, to produce carbohydrates. The plant pathogenic fungus Magnaporthe oryzae (Pyricularia oryzae) has a unique chitin deacetylase, Cbp1. The spatiotemporal activity of this protein is required for modification of the M. oryzae wall and for cell differentiation into the specialized infection structure (appressorium). Here we show that acetic acid, another product released by the Cbp1-catalyzed conversion of chitin into chitosan, induces appressorium formation. An extremely low concentration (fM) of acetic acid restored cell differentiation in a Δcbp1 mutant possibly through the glyoxylate cycle.

| S-EPMC6941858 | biostudies-literature

Functional characterization of a mitochondrial Ser/Thr protein phosphatase in cell death regulation.

Project description:Protein phosphorylation is a major form of posttranslational modification critical to cell signaling that also occurs in mitochondrial proteome. Yet, only very limited studies have been performed to characterize mitochondrial-targeted protein kinases or phosphatases. Recently, we identified a novel member of PP2C family (PP2Cm) that is a resident mitochondrial protein phosphatase which plays an important role in normal development and cell survival. In this chapter, we will describe the methods applied in the identification of PP2Cm as a resident mitochondrial protein phosphatase based on sequence analysis and biochemical characterization. We will also provide experimental protocols used to establish the intracellular localization of PP2Cm, to achieve loss and gain function of PP2Cm in cultured cells and intact tissue, and to assess the impact of PP2Cm deficiency on cell death, mitochondria oxidative phosphorylation and permeability transition pore opening.

| S-EPMC3705213 | biostudies-literature

The type 2C Ser/Thr phosphatase PP2Cgamma is a pre-mRNA splicing factor.

Project description:To identify activities involved in human pre-mRNA splicing, we have developed a procedure to separate HeLa cell nuclear extract into five complementing fractions. An activity called SCF1 was purified from one of these fractions by assaying for reconstitution of splicing in the presence of the remaining four fractions. A component of SCF1 is shown to be PP2Cgamma, a type 2C Ser/Thr phosphatase of previously unknown function. Previous work suggested that dephosphorylation of splicing factors may be important for catalysis after spliceosome assembly, although the identities of the specific phosphatases involved remain unclear. Here we show that human PP2Cgamma is physically associated with the spliceosome in vitro throughout the splicing reaction, but is first required during the early stages of spliceosome assembly for efficient formation of the A complex. The phosphatase activity is required for the splicing function of PP2Cgamma, as an active site mutant does not support spliceosome assembly. The requirement for PP2Cgamma is highly specific, as the closely related phosphatase PP2Calpha cannot substitute for PP2Cgamma. Consistent with a role in splicing, PP2Cgamma localizes to the nucleus in vivo. We conclude that at least one specific dephosphorylation event catalyzed by PP2Cgamma is required for formation of the spliceosome.

| S-EPMC316367 | biostudies-literature

Elevated levels of Ser/Thr protein phosphatase 5 (PP5) in human breast cancer.

Project description:Ser/Thr protein phosphatase 5 (PP5) regulates several signaling-cascades that suppress growth and/or facilitate apoptosis in response to genomic stress. The expression of PP5 is responsive to hypoxia inducible factor-1 (HIF-1) and estrogen, which have both been linked to the progression of human breast cancer. Still, it is not clear if PP5 plays a role in the development of human cancer. Here, immunostaining of breast cancer tissue-microarrays (TMAs) revealed a positive correlation between PP5 over-expression and ductal carcinoma in situ (DCIS; P value 0.0028), invasive ductal carcinoma (IDC; P value 0.012) and IDC with metastases at the time of diagnosis (P value 0.0001). In a mouse xenograft model, the constitutive over-expression of PP5 was associated with an increase in the rate of tumor growth. In a MCF-7 cell culture model over-expression correlated with both an increase in the rate of proliferation and protection from cell death induced by oxidative stress, UVC-irradiation, adriamycin, and vinblastine. PP5 over-expression had no apparent effect on the sensitivity of MCF-7 cells to taxol or rapamycin. Western analysis of extracts from cells over-expressing PP5 revealed a decrease in the phosphorylation of known substrates for PP5. Together, these studies indicate that elevated levels of PP5 protein occur in human breast cancer and suggest that PP5 over-expression may aid tumor progression.

| S-EPMC2505351 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data