scholarly journals MAPK Regulation of Sclerotial Development in Sclerotinia sclerotiorum Is Linked with pH and cAMP Sensing

2004 ◽  
Vol 17 (4) ◽  
pp. 404-413 ◽  
Author(s):  
Changbin Chen ◽  
Arye Harel ◽  
Rena Gorovoits ◽  
Oded Yarden ◽  
Martin B. Dickman
Keyword(s):  
Signaling Pathway ◽  
Sclerotinia Sclerotiorum ◽  
Specific Inhibitor ◽  
Broad Host Range ◽  
Environmental Signals ◽  
Mitogen Activated Protein ◽  
Fungal Phytopathogen ◽  
Ph Conditions ◽  
Sclerotial Development ◽  
Dependent Signaling Pathway

Sclerotial development is fundamental to the disease cycle of the omnivorous broad host range fungal phytopathogen Sclerotinia sclerotiorum. We have isolated a highly conserved homolog of ERK-type mitogen-activated protein kinases (MAPKs) from S. sclerotiorum (Smk1) and have demonstrated that Smk1 is required for sclerotial development. The smk1 transcription and MAPK enzyme activity are induced dramatically during sclerotiogenesis, especially during the production of sclerotial initials. When PD98059 (a specific inhibitor of the activation of MAPK by MAPK kinase) was applied to differentiating cultures or when antisense expression of smk1 was induced, sclerotial maturation was impaired. The smk1 transcript levels were highest under acidic pH conditions, suggesting that Smk1 regulates sclerotial development via a pH-dependent signaling pathway, involving the accumulation of oxalic acid, a previously identified pathogenicity factor that functions at least in part by reducing pH. Addition of cyclic AMP (cAMP) inhibited smk1 transcription, MAPK activation, and sclerotial development. Thus, S. sclerotiorum can coordinate environmental signals (such as pH) to trigger a signaling pathway mediated by Smk1 to induce sclerotia formation, and this pathway is negatively regulated by cAMP.

scholarly journals pH Signaling in Sclerotinia sclerotiorum: Identification of a pacC/RIM1 Homolog

2001 ◽  
Vol 67 (1) ◽  
pp. 75-81 ◽  
Author(s):  
Jeffrey A. Rollins ◽  
Martin B. Dickman
Keyword(s):  
Transcription Factor ◽  
Oxalic Acid ◽  
Signaling Pathway ◽  
Zinc Finger ◽  
Sclerotinia Sclerotiorum ◽  
Culture Conditions ◽  
Phytopathogenic Fungi ◽  
Molecular Signaling ◽  
Ph Conditions ◽  
Zinc Finger Domains

ABSTRACT Sclerotinia sclerotiorum acidifies its ambient environment by producing oxalic acid. This production of oxalic acid during plant infection has been implicated as a primary determinant of pathogenicity in this and other phytopathogenic fungi. We found that ambient pH conditions affect multiple processes in S. sclerotiorum. Exposure to increasing alkaline ambient pH increased the oxalic acid accumulation independent of carbon source, sclerotial development was favored by acidic ambient pH conditions but inhibited by neutral ambient pH, and transcripts encoding the endopolygalacturonase gene pg1 accumulated maximally under acidic culture conditions. We cloned a putative transcription factor-encoding gene, pac1, that may participate in a molecular signaling pathway for regulating gene expression in response to ambient pH. The three zinc finger domains of the predicted Pac1 protein are similar in sequence and organization to the zinc finger domains of the A. nidulans pH-responsive transcription factor PacC. The promoter of pac1 contains eight PacC consensus binding sites, suggesting that this gene, like its homologs, is autoregulated. Consistent with this suggestion, the accumulation ofpac1 transcripts paralleled increases in ambient pH. Pac1 was determined to be a functional homolog of PacC by complementation of an A. nidulans pacC-null strain with pac1. Our results suggest that ambient pH is a regulatory cue for processes linked to pathogenicity, development, and virulence and that these processes may be under the molecular regulation of a conserved pH-dependent signaling pathway analogous to that in the nonpathogenic fungus A. nidulans.

scholarly journals Identification and Characterization of Sclerotinia sclerotiorum NADPH Oxidases

2011 ◽  
Vol 77 (21) ◽  
pp. 7721-7729 ◽  
Author(s):  
Hyo-jin Kim ◽  
Changbin Chen ◽  
Mehdi Kabbage ◽  
Martin B. Dickman
Keyword(s):  
Sclerotinia Sclerotiorum ◽  
Fungal Pathogen ◽  
Ros Generation ◽  
Broad Host Range ◽  
Nadph Oxidases ◽  
Content Type ◽  
Beneficial Effects ◽  
Sclerotial Development ◽  
Identification And Characterization

ABSTRACTNumerous studies have shown both the detrimental and beneficial effects of reactive oxygen species (ROS) in animals, plants, and fungi. These organisms utilize controlled generation of ROS for signaling, pathogenicity, and development. Here, we show that ROS are essential for the pathogenic development ofSclerotinia sclerotiorum, an economically important fungal pathogen with a broad host range. Based on the organism's completed genome sequence, we identified twoS. sclerotiorumNADPH oxidases (SsNox1 and SsNox2), which presumably are involved in ROS generation. RNA interference (RNAi) was used to examine the function of SsNox1 and SsNox2. Silencing of SsNox1 expression indicated a central role for this enzyme in both virulence and pathogenic (sclerotial) development, while inactivation of the SsNox2 gene resulted in limited sclerotial development, but the organism remained fully pathogenic. ΔSsnox1strains had reduced ROS levels, were unable to develop sclerotia, and unexpectedly correlated with significantly reduced oxalate production. These results are in accordance with previous observations indicating that fungal NADPH oxidases are required for pathogenic development and are consistent with the importance of ROS regulation in the successful pathogenesis ofS. sclerotiorum.

scholarly journals Mitogen-Activated Protein Kinase Kinase 2, a Novel E2-Interacting Protein, Promotes the Growth of Classical Swine Fever Virus via Attenuation of the JAK-STAT Signaling Pathway

2016 ◽  
Vol 90 (22) ◽  
pp. 10271-10283 ◽  
Author(s):  
Jinghan Wang ◽  
Shucheng Chen ◽  
Yajin Liao ◽  
Enyu Zhang ◽  
Shuo Feng ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Signaling Pathway ◽  
Classical Swine Fever Virus ◽  
Specific Inhibitor ◽  
Classical Swine Fever ◽  
Fever Virus ◽  
Mitogen Activated Protein Kinase ◽  
Stat Signaling ◽  
Mitogen Activated Protein ◽  
Protein Kinase Kinase

ABSTRACTThe mitogen-activated protein kinase kinase/extracellular regulated kinase (MEK1/2/ERK1/2) cascade is involved in the replication of several members of theFlaviviridaefamily, including hepatitis C virus and dengue virus. The effects of the cascade on the replication of classical swine fever virus (CSFV), a fatal pestivirus of pigs, remain unknown. In this study, MEK2 was identified as a novel binding partner of the E2 protein of CSFV using yeast two-hybrid screening. The E2-MEK2 interaction was confirmed by glutathioneS-transferase pulldown, coimmunoprecipitation, and laser confocal microscopy assays. The C termini of E2 (amino acids [aa] 890 to 1053) and MEK2 (aa 266 to 400) were mapped to be crucial for the interaction. Overexpression of MEK2 significantly promoted the replication of CSFV, whereas knockdown of MEK2 by lentivirus-mediated small hairpin RNAs dramatically inhibited CSFV replication. In addition, CSFV infection induced a biphasic activation of ERK1/2, the downstream signaling molecules of MEK2. Furthermore, the replication of CSFV was markedly inhibited in PK-15 cells treated with U0126, a specific inhibitor for MEK1/2/ERK1/2, whereas MEK2 did not affect CSFV replication after blocking the interferon-induced Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway by ruxolitinib, a JAK-STAT-specific inhibitor. Taken together, our results indicate that MEK2 positively regulates the replication of CSFV through inhibiting the JAK-STAT signaling pathway.IMPORTANCEMitogen-activated protein kinase kinase 2 (MEK2) is a kinase that operates immediately upstream of extracellular regulated kinase 1/2 (ERK1/2) and links to Raf and ERK via phosphorylation. Currently, little is known about the role of MEK2 in the replication of classical swine fever virus (CSFV), a devastating porcine pestivirus. Here, we investigated the roles of MEK2 and the MEK2/ERK1/2 cascade in the growth of CSFV for the first time. We show that MEK2 positively regulates CSFV replication. Notably, we demonstrate that MEK2 promotes CSFV replication through inhibiting the interferon-induced JAK-STAT signaling pathway, a key antiviral pathway involved in innate immunity. Our work reveals a novel role of MEK2 in CSFV infection and sheds light on the molecular basis by which pestiviruses interact with the host cell.

scholarly journals Oxalic Acid Is an Elicitor of Plant Programmed Cell Death during Sclerotinia sclerotiorum Disease Development

2008 ◽  
Vol 21 (5) ◽  
pp. 605-612 ◽  
Author(s):  
Kyoung Su Kim ◽  
Ji-Young Min ◽  
Martin B. Dickman
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Oxalic Acid ◽  
Sclerotinia Sclerotiorum ◽  
Plant Pathogens ◽  
Broad Host Range ◽  
Disease Development ◽  
Oxygen Species ◽  
Pathogenicity Determinant ◽  
Sclerotial Development

Accumulating evidence supports the idea that necrotrophic plant pathogens interact with their hosts by controlling cell death. Sclerotinia sclerotiorum is a necrotrophic ascomycete fungus with a broad host range (>400 species). Previously, we established that oxalic acid (OA) is an important pathogenicity determinant of this fungus. In this report, we describe a mechanism by which oxalate contributes to the pathogenic success of this fungus; namely, that OA induces a programmed cell death (PCD) response in plant tissue that is required for disease development. This response exhibits features associated with mammalian apoptosis, including DNA laddering and TUNEL reactive cells. Fungal mutants deficient in OA production are nonpathogenic, and apoptotic-like characteristics are not observed following plant inoculation. The induction of PCD by OA is independent of the pH-reducing abilities of this organic acid, which is required for sclerotial development. Moreover, oxalate also induces increased reactive oxygen species (ROS) levels in the plant, which correlate to PCD. When ROS induction is inhibited, apoptotic-like cell death induced by OA does not occur. Taken together, we show that Sclerotinia spp.-secreted OA is an elicitor of PCD in plants and is responsible for induction of apoptotic-like features in the plant during disease development. This PCD is essential for fungal pathogenicity and involves ROS. Thus, OA appears to function by triggering in the plant pathways responsible for PCD. Further, OA secretion by Sclerotinia spp. is not directly toxic but, more subtly, may function as a signaling molecule.

TNF-α in Combination with Palmitate Enhances IL-8 Production via TLR4-Dependent Signaling Pathway—Potential Relevance to Metabolic Inflammation

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1730-P
Author(s):  
RASHEED AHMAD ◽  
NADEEM AKHTER ◽  
SHIHAB P. KOCHUMON ◽  
AREEJ ABU ALROUB ◽  
REEBY S. THOMAS ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Metabolic Inflammation ◽  
Tnf Α ◽  
Dependent Signaling Pathway
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