scholarly journals Distinct Regulatory Proteins Control the Graded Transcriptional Response to Increasing H2O2 Levels in Fission Yeast Schizosaccharomyces pombe

2002 ◽  
Vol 13 (3) ◽  
pp. 805-816 ◽  
Author(s):  
Janet Quinn ◽  
Victoria J. Findlay ◽  
Keren Dawson ◽  
Jonathan B.A. Millar ◽  
Nic Jones ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Protein Kinase ◽  
Schizosaccharomyces Pombe ◽  
Fission Yeast ◽  
Transcriptional Response ◽  
Regulatory Proteins ◽  
Mitogen Activated Protein Kinase ◽  
Two Component ◽  
Mitogen Activated Protein ◽  
Low Levels

The signaling pathways that sense adverse stimuli and communicate with the nucleus to initiate appropriate changes in gene expression are central to the cellular stress response. Herein, we have characterized the role of the Sty1 (Spc1) stress-activated mitogen-activated protein kinase pathway, and the Pap1 and Atf1 transcription factors, in regulating the response to H2O2 in the fission yeast Schizosaccharomyces pombe. We find that H2O2 activates the Sty1 pathway in a dose-dependent manner via at least two sensing mechanisms. At relatively low levels of H2O2, a two component-signaling pathway, which feeds into either of the two stress-activated mitogen-activated protein kinase kinase kinases Wak1 or Win1, regulates Sty1 phosphorylation. In contrast, at high levels of H2O2, Sty1 activation is controlled predominantly by a two-component independent mechanism and requires the function of both Wak1 and Win1. Individual transcription factors were also found to function within a limited range of H2O2 concentrations. Pap1 activates target genes primarily in response to low levels of H2O2, whereas Atf1 primarily controls the transcriptional response to high concentrations of H2O2. Our results demonstrate that S. pombe uses a combination of stress-responsive regulatory proteins to gauge and effect the appropriate transcriptional response to increasing concentrations of H2O2.

Different roles for the stress-activated protein kinase pathway in the regulation of trehalose metabolism in Schizosaccharomyces pombe

Microbiology ◽  
2003 ◽  
Vol 149 (7) ◽  
pp. 1745-1752 ◽  
Author(s):  
V. Paredes ◽  
A. Franco ◽  
T. Soto ◽  
J. Vicente-Soler ◽  
M. Gacto ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
Protein Kinase ◽  
Osmotic Stress ◽  
Schizosaccharomyces Pombe ◽  
Fission Yeast ◽  
Stress Responses ◽  
Mitogen Activated Protein Kinase ◽  
Wide Range ◽  
Trehalose Metabolism

The Wis1p-Sty1p mitogen-activated protein kinase cascade is a major signalling system in the fission yeast Schizosaccharomyces pombe for a wide range of stress responses. It is known that trehalose functions as a protective metabolite to counteract deleterious effects of environmental stresses. Herein it is reported that the expression of genes related to trehalose metabolism in S. pombe, ntp1 + (neutral trehalase) and tps1 + [trehalose-6-phosphate (T6P) synthase], is partially regulated by the Sty1p kinase under salt-induced osmotic stress and conditions of slight oxidative stress and is fully dependent on this kinase under severe oxidative stress. This control is carried out through transcription factors Atf1p/Pcr1p during osmotic stress and through Pap1p during exposure to low levels of oxidative stress. However, all three transcription factors are needed for gene expression under conditions of extreme oxidative stress. In addition, a role for Sty1p in the modulation of post-transcriptional activation of trehalase mediated by Pka1p/Sck1p kinases, as well as in the activity of T6P synthase under such stressful conditions has been demonstrated. These results reveal a novel dual action of the Wis1p-Sty1p pathway in the regulation of trehalose metabolism in fission yeast.

scholarly journals Transduction of centrifugation-induced gravity forces through mitogen-activated protein kinase pathways in the fission yeast Schizosaccharomyces pombe

Microbiology ◽  
2007 ◽  
Vol 153 (5) ◽  
pp. 1519-1529 ◽  
Author(s):  
Teresa. Soto ◽  
Andrés. Núñez ◽  
Marisa. Madrid ◽  
Jero. Vicente ◽  
Mariano. Gacto ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Schizosaccharomyces Pombe ◽  
Fission Yeast ◽  
Mitogen Activated Protein Kinase ◽  
Induced Gravity ◽  
Gravity Forces ◽  
Mitogen Activated Protein

scholarly journals Molecular Modeling of Differentially Phosphorylated Serine 10 and Acetylated lysine 9/14 of Histone H3 Regulates their Interactions with 14-3-3ζ, MSK1, and MKP1

2013 ◽  
Vol 7 ◽  
pp. BBI.S12449 ◽  
Author(s):  
Ajit K. Sharma ◽  
Abhilasha Mansukh ◽  
Ashok Varma ◽  
Nikhil Gadewal ◽  
Sanjay Gupta
Keyword(s):  
Molecular Modeling ◽  
Protein Kinase ◽  
Chromatin Structure ◽  
In Silico ◽  
Association Studies ◽  
Regulatory Proteins ◽  
Mitogen Activated Protein Kinase ◽  
Site Specific ◽  
Mitogen Activated Protein ◽  
Neighboring Site

Histone modifications occur in precise patterns, with several modifications known to affect the binding of proteins. These interactions affect the chromatin structure, gene regulation, and cell cycle events. The dual modifications on the H3 tail, serine10 phosphorylation, and lysine14 acetylation (H3Ser10PLys14Ac) are reported to be crucial for interaction with 14-3-3ζ. However, the mechanism by which H3Ser10P along with neighboring site-specific acetylation(s) is targeted by its regulatory proteins, including kinase and phosphatase, is not fully understood. We carried out molecular modeling studies to understand the interaction of 14-3-3ζ, and its regulatory proteins, mitogen-activated protein kinase phosphatase-1 (MKP1), and mitogen- and stress-activated protein kinase-1 (MSK1) with phosphorylated H3Ser10 alone or in combination with acetylated H3Lys9 and Lys14. In silico molecular association studies suggested that acetylated Lys14 and phosphorylated Ser10 of H3 shows the highest binding affinity towards 14-3-3ζ. In addition, acetylation of H3Lys9 along with Ser10PLys14Ac favors the interaction of the phosphatase, MKP1, for dephosphorylation of H3Ser10P. Further, MAP kinase, MSK1 phosphorylates the unmodified H3Ser10 containing N-terminal tail with maximum affinity compared to the N-terminal tail with H3Lys9AcLys14Ac. The data clearly suggest that opposing enzymatic activity of MSK1 and MKP1 corroborates with non-acetylated and acetylated, H3Lys9Lys14, respectively. Our in silico data highlights that site-specific phosphorylation (H3Ser10P) and acetylation (H3Lys9 and H3Lys14) of H3 are essential for the interaction with their regulatory proteins (MKP1, MSK1, and 14-3-3ζ) and plays a major role in the regulation of chromatin structure.

scholarly journals A Redox-Sensitive Thiol in Wis1 Modulates the Fission Yeast Mitogen-Activated Protein Kinase Response to H2O2 and Is the Target of a Small Molecule

2020 ◽  
Vol 40 (7) ◽  
Author(s):  
Johanna J. Sjölander ◽  
Agata Tarczykowska ◽  
Cecilia Picazo ◽  
Itziar Cossio ◽  
Itedale Namro Redwan ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Fission Yeast ◽  
Inhibitory Effect ◽  
Mitogen Activated Protein Kinase ◽  
Activation Loop ◽  
Content Type ◽  
Kinase Activation ◽  
Mitogen Activated Protein

ABSTRACT Oxidation of a highly conserved cysteine (Cys) residue located in the kinase activation loop of mitogen-activated protein kinase kinases (MAPKK) inactivates mammalian MKK6. This residue is conserved in the fission yeast Schizosaccharomyces pombe MAPKK Wis1, which belongs to the H2O2-responsive MAPK Sty1 pathway. Here, we show that H2O2 reversibly inactivates Wis1 through this residue (C458) in vitro. We found that C458 is oxidized in vivo and that serine replacement of this residue significantly enhances Wis1 activation upon addition of H2O2. The allosteric MAPKK inhibitor INR119, which binds in a pocket next to the activation loop and C458, prevented the inhibition of Wis1 by H2O2 in vitro and significantly increased Wis1 activation by low levels of H2O2 in vivo. We propose that oxidation of C458 inhibits Wis1 and that INR119 cancels out this inhibitory effect by binding close to this residue. Kinase inhibition through the oxidation of a conserved Cys residue in MKK6 (C196) is thus conserved in the S. pombe MAPKK Wis1.

scholarly journals Transcriptomic and Network Analysis Identifies Shared and Unique Pathways across Dementia Spectrum Disorders

2020 ◽  
Vol 21 (6) ◽  
pp. 2050 ◽  
Author(s):  
Jose A. Santiago ◽  
Virginie Bottero ◽  
Judith A. Potashkin
Keyword(s):  
Transcription Factors ◽  
Protein Kinase ◽  
Mapk Signaling ◽  
Pentose Phosphate ◽  
Mitogen Activated Protein Kinase ◽  
Health Concern ◽  
Mitogen Activated Protein ◽  
Common Etiology ◽  
Nuclear Factor Kappa Beta ◽  
Upregulated Genes

Background: Dementia is a growing public health concern with an estimated prevalence of 50 million people worldwide. Alzheimer’s disease (AD) and vascular and frontotemporal dementias (VaD, FTD), share many clinical, genetical, and pathological features making the diagnosis difficult. Methods: In this study, we compared the transcriptome from the frontal cortex of patients with AD, VaD, and FTD to identify dysregulated pathways. Results: Upregulated genes in AD were enriched in adherens and tight junctions, mitogen-activated protein kinase, and phosphatidylinositol 3-kinase and protein kinase B/Akt signaling pathways, whereas downregulated genes associated with calcium signaling. Upregulated genes in VaD were centered on infectious diseases and nuclear factor kappa beta signaling, whereas downregulated genes are involved in biosynthesis of amino acids and the pentose phosphate pathway. Upregulated genes in FTD were associated with ECM receptor interactions and the lysosome, whereas downregulated genes were involved in glutamatergic synapse and MAPK signaling. The transcription factor KFL4 was shared among the 3 types of dementia. Conclusions: Collectively, we identified similarities and differences in dysregulated pathways and transcription factors among the dementias. The shared pathways and transcription factors may indicate a potential common etiology, whereas the differences may be useful for distinguishing dementias.

scholarly journals The MAPK Hog1p Modulates Fps1p-dependent Arsenite Uptake and Tolerance in Yeast

2006 ◽  
Vol 17 (10) ◽  
pp. 4400-4410 ◽  
Author(s):  
Michael Thorsen ◽  
Yujun Di ◽  
Carolina Tängemo ◽  
Montserrat Morillas ◽  
Doryaneh Ahmadpour ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Transcriptional Response ◽  
Mitogen Activated Protein Kinase ◽  
Regulatory Mechanisms ◽  
Signaling Mechanisms ◽  
Mitogen Activated Protein ◽  
Detoxification Systems ◽  
Arsenic Sensing

Arsenic is widely distributed in nature and all organisms possess regulatory mechanisms to evade toxicity and acquire tolerance. Yet, little is known about arsenic sensing and signaling mechanisms or about their impact on tolerance and detoxification systems. Here, we describe a novel role of the S. cerevisiae mitogen-activated protein kinase Hog1p in protecting cells during exposure to arsenite and the related metalloid antimonite. Cells impaired in Hog1p function are metalloid hypersensitive, whereas cells with elevated Hog1p activity display improved tolerance. Hog1p is phosphorylated in response to arsenite and this phosphorylation requires Ssk1p and Pbs2p. Arsenite-activated Hog1p remains primarily cytoplasmic and does not mediate a major transcriptional response. Instead, hog1Δ sensitivity is accompanied by elevated cellular arsenic levels and we demonstrate that increased arsenite influx is dependent on the aquaglyceroporin Fps1p. Fps1p is phosphorylated on threonine 231 in vivo and this phosphorylation critically affects Fps1p activity. Moreover, Hog1p is shown to affect Fps1p phosphorylation. Our data are the first to demonstrate Hog1p activation by metalloids and provides a mechanism by which this kinase contributes to tolerance acquisition. Understanding how arsenite/antimonite uptake and toxicity is modulated may prove of value for their use in medical therapy.

scholarly journals Biological Significance of Nuclear Localization of Mitogen-activated Protein Kinase Pmk1 in Fission Yeast

2012 ◽  
Vol 287 (31) ◽  
pp. 26038-26051 ◽  
Author(s):  
Laura Sánchez-Mir ◽  
Alejandro Franco ◽  
Marisa Madrid ◽  
Jero Vicente-Soler ◽  
M. Antonia Villar-Tajadura ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Fission Yeast ◽  
Nuclear Localization ◽  
Biological Significance ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein

scholarly journals Stress-Activated Protein Kinase Pathway Functions To Support Protein Synthesis and Translational Adaptation in Response to Environmental Stress in Fission Yeast

2005 ◽  
Vol 4 (11) ◽  
pp. 1785-1793 ◽  
Author(s):  
Isabelle Dunand-Sauthier ◽  
Carol A. Walker ◽  
Jana Narasimhan ◽  
Amanda K. Pearce ◽  
Ronald C. Wek ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Protein Kinase ◽  
Osmotic Stress ◽  
Environmental Stress ◽  
Fission Yeast ◽  
Translation Initiation ◽  
Mitogen Activated Protein Kinase ◽  
Wild Type ◽  
Eif2α Phosphorylation ◽  
Mitogen Activated Protein

ABSTRACT The stress-activated protein kinase (SAPK) pathway plays a central role in coordinating gene expression in response to diverse environmental stress stimuli. We examined the role of this pathway in the translational response to stress in Schizosaccharomyces pombe. Exposing wild-type cells to osmotic stress (KCl) resulted in a rapid but transient reduction in protein synthesis. Protein synthesis was further reduced in mutants disrupting the SAPK pathway, including the mitogen-activated protein kinase Wis1 or the mitogen-activated protein kinase Spc1/Sty1, suggesting a role for these stress response factors in this translational control. Further polysome analyses revealed a role for Spc1 in supporting translation initiation during osmotic stress, and additionally in facilitating translational adaptation. Exposure to oxidative stress (H2O2) resulted in a striking reduction in translation initiation in wild-type cells, which was further reduced in spc1 − cells. Reduced translation initiation correlated with phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2α) in wild-type cells. Disruption of Wis1 or Spc1 kinase or the downstream bZip transcription factors Atf1 and Pap1 resulted in a marked increase in eIF2α phosphorylation which was dependent on the eIF2α kinases Hri2 and Gcn2. These findings suggest a role for the SAPK pathway in supporting translation initiation and facilitating adaptation to environmental stress in part through reducing eIF2α phosphorylation in fission yeast.

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