scholarly journals Regulation of theCandida albicansCell Wall Damage Response by Transcription Factor Sko1 and PAS Kinase Psk1

2008 ◽  
Vol 19 (7) ◽  
pp. 2741-2751 ◽  
Author(s):  
Jason M. Rauceo ◽  
Jill R. Blankenship ◽  
Saranna Fanning ◽  
Jessica J. Hamaker ◽  
Jean-Sebastien Deneault ◽  
...  
Keyword(s):  
Cell Wall ◽  
Transcription Factor ◽  
Protein Kinase ◽  
Osmotic Stress ◽  
Signal Transduction Pathway ◽  
Environmental Niche ◽  
Regulatory Pathways ◽  
Pas Kinase ◽  
Cell Wall Inhibition ◽  
Inducible Genes

The environmental niche of each fungus places distinct functional demands on the cell wall. Hence cell wall regulatory pathways may be highly divergent. We have pursued this hypothesis through analysis of Candida albicans transcription factor mutants that are hypersensitive to caspofungin, an inhibitor of beta-1,3-glucan synthase. We report here that mutations in SKO1 cause this phenotype. C. albicans Sko1 undergoes Hog1-dependent phosphorylation after osmotic stress, like its Saccharomyces cerevisiae orthologues, thus arguing that this Hog1-Sko1 relationship is conserved. However, Sko1 has a distinct role in the response to cell wall inhibition because 1) sko1 mutants are much more sensitive to caspofungin than hog1 mutants; 2) Sko1 does not undergo detectable phosphorylation in response to caspofungin; 3) SKO1 transcript levels are induced by caspofungin in both wild-type and hog1 mutant strains; and 4) sko1 mutants are defective in expression of caspofungin-inducible genes that are not induced by osmotic stress. Upstream Sko1 regulators were identified from a panel of caspofungin-hypersensitive protein kinase–defective mutants. Our results show that protein kinase Psk1 is required for expression of SKO1 and of Sko1-dependent genes in response to caspofungin. Thus Psk1 and Sko1 lie in a newly described signal transduction pathway.

scholarly journals Transcriptional Coregulation by the Cell Integrity Mitogen-Activated Protein Kinase Slt2 and the Cell Cycle Regulator Swi4

2001 ◽  
Vol 21 (19) ◽  
pp. 6515-6528 ◽  
Author(s):  
Kristin Baetz ◽  
Jason Moffat ◽  
Jennifer Haynes ◽  
Michael Chang ◽  
Brenda Andrews
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Wall ◽  
Transcription Factor ◽  
Protein Kinase ◽  
Mapk Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Regulatory Subunit ◽  
Cell Integrity ◽  
Mitogen Activated Protein

ABSTRACT In Saccharomyces cerevisiae, the heterodimeric transcription factor SBF (for SCB binding factor) is composed of Swi4 and Swi6 and activates gene expression at the G1/S-phase transition of the mitotic cell cycle. Cell cycle commitment is associated not only with major alterations in gene expression but also with highly polarized cell growth; the mitogen-activated protein kinase (MAPK) Slt2 is required to maintain cell wall integrity during periods of polarized growth and cell wall stress. We describe experiments aimed at defining the regulatory pathway involving the cell cycle transcription factor SBF and Slt2-MAPK. Gene expression assays and chromatin immunoprecipitation experiments revealed Slt2-dependent recruitment of SBF to the promoters of the G1 cyclinsPCL1 and PCL2 after activation of the Slt2-MAPK pathway. We performed DNA microarray analysis and identified other genes whose expression was reduced in both SLT2and SWI4 deletion strains. Genes that are sensitive to both Slt2 and Swi4 appear to be uniquely regulated and reveal a role for Swi4, the DNA-binding component of SBF, which is independent of the regulatory subunit Swi6. Some of the Swi4- and Slt2-dependent genes do not require Swi6 for either their expression or for Swi4 localization to their promoters. Consistent with these results, we found a direct interaction between Swi4 and Slt2. Our results establish a new Slt2-dependent mode of Swi4 regulation and suggest roles for Swi4 beyond its prominent role in controlling cell cycle transcription.

scholarly journals Mechanism of Mpk1 Mitogen-Activated Protein Kinase Binding to the Swi4 Transcription Factor and Its Regulation by a Novel Caffeine-Induced Phosphorylation

2009 ◽  
Vol 29 (24) ◽  
pp. 6449-6461 ◽  
Author(s):  
Andrew W. Truman ◽  
Ki-Young Kim ◽  
David E. Levin
Keyword(s):  
Cell Wall ◽  
Transcription Factor ◽  
Protein Kinase ◽  
Dna Binding ◽  
Binding Site ◽  
Mutational Analysis ◽  
Cell Wall Integrity ◽  
Mitogen Activated Protein Kinase ◽  
Activation Mechanism ◽  
Mitogen Activated Protein

ABSTRACT The Mpk1 mitogen-activated protein kinase (MAPK) of the cell wall integrity signaling pathway uses a noncatalytic mechanism to activate the SBF (Swi4/Swi6) transcription factor. Active Mpk1 forms a complex with Swi4, the DNA-binding subunit of SBF, conferring the ability to bind DNA. Because SBF activation is independent of Mpk1 catalytic activity but requires Mpk1 to be in an active conformation, we sought to understand how Mpk1 interacts with Swi4. Mutational analysis revealed that binding and activation of Swi4 by Mpk1 requires an intact D-motif-binding site, a docking surface common to MAPKs that resides distal to the phosphorylation loop but does not require the substrate-binding site, revealing a novel mechanism for MAPK target regulation. Additionally, we found that Mpk1 binds near the autoinhibitory C terminus of Swi4, suggesting an activation mechanism in which Mpk1 substitutes for Swi6 in promoting Swi4 DNA binding. Finally, we show that caffeine is an atypical activator of cell wall integrity signaling, because it induces phosphorylation of the Mpk1 C-terminal extension at Ser423 and Ser428. These phosphorylations were dependent on the DNA damage checkpoint kinases, Mec1/Tel1 and Rad53. Phosphorylation of Ser423 specifically blocked SBF activation by preventing Mpk1 association with Swi4, revealing a novel mechanism for regulating MAPK target specificity.

scholarly journals Glucocorticoids and protein kinase A coordinately modulate transcription factor recruitment at a glucocorticoid-responsive unit.

1995 ◽  
Vol 15 (10) ◽  
pp. 5346-5354 ◽  
Author(s):  
M L Espinás ◽  
J Roux ◽  
R Pictet ◽  
T Grange
Keyword(s):  
Transcription Factor ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Cell Lines ◽  
Transcription Factor Binding ◽  
Tyrosine Aminotransferase ◽  
Dependent Manner ◽  
Regulatory Pathways ◽  
Factor Binding ◽  
Kinase A

The rat tyrosine aminotransferase gene is a model system to study transcriptional regulation by glucocorticoid hormones. We analyzed transcription factor binding to the tyrosine aminotransferase gene glucocorticoid-responsive unit (GRU) at kb -2.5, using in vivo footprinting studies with both dimethyl sulfate and DNase I. At this GRU, glucocorticoid activation triggers a disruption of the nucleosomal structure. We show here that various regulatory pathways affect transcription factor binding to this GRU. The binding differs in two closely related glucocorticoid-responsive hepatoma cell lines. In line H4II, glucocorticoid induction promotes the recruitment of hepatocyte nuclear factor 3 (HNF3), presumably through the nucleosomal disruption. However, the footprint of the glucocorticoid receptor (GR) is not visible, even though a regular but transient interaction of the GR is necessary to maintain HNF3 binding. In contrast, in line FTO2B, HNF3 binds to the GRU in the absence of glucocorticoids and nucleosomal disruption, showing that a "closed" chromatin conformation does not repress the binding of certain transcription factors in a uniform manner. In FTO2B cells, the footprint of the GR is detectable, but this requires the activation of protein kinase A. In addition, protein kinase A stimulation also improves the recruitment of HNF3 independently of glucocorticoids and enhances the glucocorticoid response mediated by this GRU in an HNF3-dependent manner. In conclusion, the differences in the behavior of this regulatory sequence in the two cell lines show that various regulatory pathways are integrated at this GRU through modulation of interrelated events: transcription factor binding to DNA and nucleosomal disruption.

scholarly journals Involvement of the Pleiotropic Drug Resistance Response, Protein Kinase C Signaling, and Altered Zinc Homeostasis in Resistance of Saccharomyces cerevisiae to Diclofenac

2011 ◽  
Vol 77 (17) ◽  
pp. 5973-5980 ◽  
Author(s):  
Jolanda S. van Leeuwen ◽  
Nico P. E. Vermeulen ◽  
J. Chris Vos
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Drug Resistance ◽  
Cell Wall ◽  
Transcription Factor ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Zinc Homeostasis ◽  
Yeast Cells ◽  
Pleiotropic Drug Resistance ◽  
Kinase C

ABSTRACTDiclofenac is a widely used analgesic drug that can cause serious adverse drug reactions. We usedSaccharomyces cerevisiaeas a model eukaryote with which to elucidate the molecular mechanisms of diclofenac toxicity and resistance. Although most yeast cells died during the initial diclofenac treatment, some survived and started growing again. Microarray analysis of the adapted cells identified three major processes involved in diclofenac detoxification and tolerance. In particular, pleiotropic drug resistance (PDR) genes and genes under the control of Rlm1p, a transcription factor in the protein kinase C (PKC) pathway, were upregulated in diclofenac-adapted cells. We tested if these processes or pathways were directly involved in diclofenac toxicity or resistance. Of the pleiotropic drug resistance gene products, the multidrug transporter Pdr5p was crucially important for diclofenac tolerance. Furthermore, deletion of components of the cell wall stress-responsive PKC pathway increased diclofenac toxicity, whereas incubation of cells with the cell wall stressor calcofluor white before the addition of diclofenac decreased its toxicity. Also, diclofenac induced flocculation, which might trigger the cell wall alterations. Genes involved in ribosome biogenesis and rRNA processing were downregulated, as were zinc-responsive genes. Paradoxically, deletion of the zinc-responsive transcription factor Zap1p or addition of the zinc chelator 1,10-phenanthroline significantly increased diclofenac toxicity, establishing a regulatory role for zinc in diclofenac resistance. In conclusion, we have identified three new pathways involved in diclofenac tolerance in yeast, namely, Pdr5p as the main contributor to the PDR response, cell wall signaling via the PKC pathway, and zinc homeostasis, regulated by Zap1p.

scholarly journals Slt2p phosphorylation induces cyclin C nuclear-to-cytoplasmic translocation in response to oxidative stress

2014 ◽  
Vol 25 (8) ◽  
pp. 1396-1407 ◽  
Author(s):  
Chunyan Jin ◽  
Randy Strich ◽  
Katrina F. Cooper
Keyword(s):  
Transcription Factor ◽  
Protein Kinase ◽  
Cell Fate ◽  
Mitochondrial Fission ◽  
Signal Transduction Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Downstream Effectors ◽  
Cyclin C ◽  
Mitogen Activated Protein ◽  
Cytoplasmic Translocation

The yeast C-type cyclin represses the transcription of genes required for the stress response and meiosis. To relieve this repression, cyclin C undergoes nuclear-to-cytoplasmic translocation in response to many stressors, including hydrogen peroxide, where it is destroyed by ubiquitin-mediated proteolysis. Before its destruction, cyclin C promotes stress-induced mitochondrial fission and programmed cell death, indicating that relocalization is an important cell fate regulator. Here we show that cyclin C cytoplasmic translocation requires the cell wall integrity (CWI) mitogen-activated protein kinase Slt2p, its pseudokinase paralogue, Kdx1p, and an associating transcription factor, Ask10p. Furthermore, Slt2p and Kdx1p regulate cyclin C stability through different but required mechanisms. Slt2p associates with, and directly phosphorylates, cyclin C at Ser-266. Eliminating or mimicking phosphorylation at this site restricts or enhances cyclin C cytoplasmic translocation and degradation, respectively. Conversely, Kdx1p does not bind cyclin C but instead coimmunoprecipitates with Ask10p, a transcription factor previously identified as a regulator of cyclin C destruction. These results reveal a complex regulatory circuitry involving both downstream effectors of the CWI mitogen-activated protein kinase signal transduction pathway to target the relocalization and consequent destruction of a single transcriptional repressor.

scholarly journals Targeting the MEF2-Like Transcription Factor Smp1 by the Stress-Activated Hog1 Mitogen-Activated Protein Kinase

2003 ◽  
Vol 23 (1) ◽  
pp. 229-237 ◽  
Author(s):  
Eulàlia de Nadal ◽  
Laura Casadomé ◽  
Francesc Posas
Keyword(s):  
Transcription Factor ◽  
Protein Kinase ◽  
Osmotic Stress ◽  
Stationary Phase ◽  
Osmotic Shock ◽  
Critical Role ◽  
Mitogen Activated Protein Kinase ◽  
Yeast Cells ◽  
Dependent Manner ◽  
Mitogen Activated Protein

ABSTRACT Exposure of Saccharomyces cerevisiae to increases in extracellular osmolarity activates the stress-activated Hog1 mitogen-activated protein kinase (MAPK), which is essential for cell survival upon osmotic stress. Yeast cells respond to osmotic stress by inducing the expression of a very large number of genes, and the Hog1 MAPK plays a critical role in gene transcription upon stress. To understand how Hog1 controls gene expression, we designed a genetic screen to isolate new transcription factors under the control of the MAPK and identified the MEF2-like transcription factor, Smp1, as a target for Hog1. Overexpression of SMP1 induced Hog1-dependent expression of osmoresponsive genes such as STL1, whereas smp1Δ cells were defective in their expression. Consistently, smp1Δ cells displayed reduced viability upon osmotic shock. In vivo coprecipitation and phosphorylation studies showed that Smp1 and Hog1 interact and that Smp1 is phosphorylated upon osmotic stress in a Hog1-dependent manner. Hog1 phosphorylated Smp1 in vitro at the C-terminal region. Phosphorylation of Smp1 by the MAPK is essential for its function, since a mutant allele unable to be phosphorylated by the MAPK displays impaired stress responses. Thus, our data indicate that Smp1 acts downstream of Hog1, controlling a subset of the responses induced by the MAPK. Moreover, Smp1 concentrates in the nucleus during the stationary phase, and the lack of SMP1 results in cells that lose viability in the stationary phase. Localization of Smp1 depends on HOG1, and consistently, hog1Δ cells also lose viability during this growth phase. These data suggest that Smp1 could be mediating a role for the Hog1 MAPK during the stationary phase.

scholarly journals Saccharomyces cerevisiae Heat Shock Transcription Factor Regulates Cell Wall Remodeling in Response to Heat Shock

2005 ◽  
Vol 4 (6) ◽  
pp. 1050-1056 ◽  
Author(s):  
Hiromi Imazu ◽  
Hiroshi Sakurai
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Wall ◽  
Transcription Factor ◽  
Heat Shock ◽  
Protein Kinase ◽  
Elevated Temperatures ◽  
Heat Shock Transcription Factor ◽  
Mitogen Activated Protein Kinase ◽  
Temperature Sensitive ◽  
Cell Wall Remodeling

ABSTRACT The heat shock transcription factor Hsf1 of the yeast Saccharomyces cerevisiae regulates expression of genes encoding heat shock proteins and a variety of other proteins as well. To better understand the cellular roles of Hsf1, we screened multicopy suppressor genes of a temperature-sensitive hsf1 mutation. The RIM15 gene, encoding a protein kinase that is negatively regulated by the cyclic AMP-dependent protein kinase, was identified as a suppressor, but Rim15-regulated stress-responsive transcription factors, such as Msn2, Msn4, and Gis1, were unable to rescue the temperature-sensitive growth phenotype of the hsf1 mutant. Another class of suppressors encoded cell wall stress sensors, Wsc1, Wsc2, and Mid2, and the GDP/GTP exchange factor Rom2 that interacts with these cell wall sensors. Activation of a protein kinase, Pkc1, which is induced by these cell wall sensor proteins upon heat shock, but not activation of the Pkc1-regulated mitogen-activated protein kinase cascade, was necessary for the hsf1 suppression. Like Wsc-Pkc1 pathway mutants, hsf1 cells exhibited an osmotic remedial cell lysis phenotype at elevated temperatures. Several of the other suppressors were found to encode proteins functioning in cell wall organization. These results suggest that Hsf1 in concert with Pkc1 regulates cell wall remodeling in response to heat shock.

scholarly journals Rice (Oryza Sativa L.) Whole Grain Genome-Wide Association Study for Neutral Sugar Content

2021 ◽  
Author(s):  
Rahele Panahabadi ◽  
Lauren S. McKee ◽  
Asadollah Ahmadikhah ◽  
Pär K. Ingvarsson ◽  
Naser Farrokhi
Keyword(s):  
Cell Wall ◽  
Transcription Factor ◽  
Protein Kinase ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Arabinogalactan Protein ◽  
Whole Grain ◽  
Genome Wide ◽  
Cell Wall Matrix

Abstract Background Cell wall matrix polysaccharides are structurally complex and diverse, but our knowledge about their synthesis is limited. The building blocks (monosaccharides) of these polysaccharides have critical role in defining the number and the ultrastructure (size) of rice grains, and therefore would have great influence on seed vigor, yield and quality. Genome-wide association study (GWAS) is a method of choice for fine mapping of QTLs involved in defining plant cell wall structure and modifications. The monosaccharides that contribute to major cell wall matrix polysaccharides in whole grains of 197 rice accessions were quantified using acid hydrolysis and high-performance anion-exchange chromatography with pulsed amperometric detection. A GWAS of calculated monosaccharide content in rice whole grain (RWG) was carried out using 33,812 single-nucleotide polymorphisms (SNPs) to identify corresponding markers in 200 kbp flanking regions.Results In total, 49 significant SNPs contained in 19 genomic regions (QTLs) on eight chromosomes of rice were determined to be associated with monosaccharides content. The candidate genes in QTL regions included the following: arabinose content was associated with α-N-arabinofuranosidase, pectinesterase inhibitor, a glycoside hydrolase (GH) from family 16 (GH16 enzyme); xylose content was associated with ethylene-responsive element-binding protein and a pyruvate kinase; mannose content was associated with a MYB family transcription factor and S-domain receptor-like protein kinase; galactose content was associated with a glycocyltransferase (GT) from family 8 (GT8 enzyme), GRAS family transcription factor, glutathione S-transferase, GH16 and GH17 enzymes; fucose content was associated with a GH16 enzyme, lysine-rich arabinogalactan protein 19 and a receptor protein kinase; and finally rhamnose content was associated with OsFBX41, pectinesterase, COBRA-like protein, and OsSAUR13 (Auxin-responsive SAUR).Conclusion The results of this study should improve our understanding of the genetic basis of the factors that might be involved in the biosynthesis and turnover of major matrix polysaccharides present in RWG. Several QTLs were identified on different chromosomes, all are reported for first. Further, our data provide insight that will be useful in the design of future breeding programs, allowing breeders to use available genetic resources more effectively in meeting global food demand and supply.

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