scholarly journals Identification and Characterization of Plant Cell Death–Inducing Secreted Proteins From Ustilaginoidea virens

2016 ◽  
Vol 29 (5) ◽  
pp. 405-416 ◽  
Author(s):  
Anfei Fang ◽  
Yanqing Han ◽  
Nan Zhang ◽  
Min Zhang ◽  
Lijuan Liu ◽  
...  
Keyword(s):  
Cell Death ◽  
Active Sites ◽  
Secreted Proteins ◽  
Ustilaginoidea Virens ◽  
Induce Cell Death ◽  
Functional Studies ◽  
Secretion Signal ◽  
Villosiclava Virens ◽  
Catalytic Active Sites ◽  
Trigger Cell Death

Ustilaginoidea virens (Cooke) Takah (telemorph Villosiclava virens) is an ascomycetous fungus that causes rice false smut, one of the most important rice diseases. Fungal effectors often play essential roles in host-pathogen coevolutionary interactions. However, little is known about the functions of U. virens effectors. Here, we performed functional studies on putative effectors in U. virens and demonstrated that 13 of 119 putative effectors caused necrosis or necrosis-like phenotypes in Nicotiana benthamiana. Among them, 11 proteins were confirmed to be secreted, using a yeast secretion system, and the corresponding genes are all highly induced during infection, except UV_44 and UV_4753. Eight secreted proteins were proven to trigger cell death or defenses in rice protoplasts and the secretion signal of these proteins is essential for their cell death–inducing activity. The ability of UV_44 and UV_1423 to trigger cell death is dependent on the predicted serine peptidase and ribonuclease catalytic active sites, respectively. We demonstrated that UV_1423 and UV_6205 are N-glycosylated proteins, which glycosylation has different impacts on their abilities to induce cell death. Collectively, the study identified multiple secreted proteins in U. virens with specific structural motifs that induce cell death or defense machinery in nonhost and host plants.

scholarly journals Apoplastic effector candidates of a foliar forest pathogen trigger cell death in host and non-host plants

2021 ◽  
Author(s):  
Lukas Hunziker ◽  
Mariana Tarallo ◽  
Keiko Gough ◽  
Melissa Guo ◽  
Cathy Hargreaves ◽  
...  
Keyword(s):  
Cell Death ◽  
Host Plants ◽  
Secreted Proteins ◽  
Natural Forests ◽  
Crop Species ◽  
Forest Pathogen ◽  
Immune Receptors ◽  
Forest Pathogens ◽  
Dothistroma Needle Blight ◽  
Trigger Cell Death

Forests are under threat from pests, pathogens, and changing climate. One of the major forest pathogens worldwide is Dothistroma septosporum, which causes dothistroma needle blight (DNB) of pines. D. septosporum is a hemibiotrophic fungus related to well-studied Dothideomycete pathogens, such as Cladosporium fulvum. These pathogens use small secreted proteins, termed effectors, to facilitate the infection of their hosts. The same effectors, however, can be recognised by plants carrying corresponding immune receptors, resulting in resistance responses. Hence, effectors are increasingly being exploited to identify and select disease resistance in crop species. In gymnosperms, however, such research is scarce. We predicted and investigated apoplastic D. septosporum candidate effectors (DsCEs) using bioinformatics and plant-based experiments. We discovered secreted proteins that trigger cell death in the angiosperm Nicotiana spp., suggesting their recognition by immune receptors in non-host plants. In a first for foliar forest pathogens, we also developed a novel protein infiltration method to show that tissue-cultured pine shoots can respond with a cell death response to one of our DsCEs, as well as to a reference cell death-inducing protein. These results contribute to our understanding of forest pathogens and may ultimately provide clues to disease immunity in both commercial and natural forests.

scholarly journals c-di-GMP induction ofDictyosteliumcell death requires the polyketide DIF-1

2015 ◽  
Vol 26 (4) ◽  
pp. 651-658 ◽  
Author(s):  
Yu Song ◽  
Marie-Françoise Luciani ◽  
Corinne Giusti ◽  
Pierre Golstein
Keyword(s):  
Cell Death ◽  
Infected Animal ◽  
Model Organism ◽  
Dictyostelium Cell ◽  
Animal Cells ◽  
Induce Cell Death ◽  
Cell Monolayers ◽  
Developmental Cell Death ◽  
Trigger Cell Death

Cell death in the model organism Dictyostelium, as studied in monolayers in vitro, can be induced by the polyketide DIF-1 or by the cyclical dinucleotide c-di-GMP. c-di-GMP, a universal bacterial second messenger, can trigger innate immunity in bacterially infected animal cells and is involved in developmental cell death in Dictyostelium. We show here that c-di-GMP was not sufficient to induce cell death in Dictyostelium cell monolayers. Unexpectedly, it also required the DIF-1 polyketide. The latter could be exogenous, as revealed by a telling synergy between c-di-GMP and DIF-1. The required DIF-1 polyketide could also be endogenous, as shown by the inability of c-di-GMP to induce cell death in Dictyostelium HMX44A cells and DH1 cells upon pharmacological or genetic inhibition of DIF-1 biosynthesis. In these cases, c-di-GMP–induced cell death was rescued by complementation with exogenous DIF-1. Taken together, these results demonstrated that c-di-GMP could trigger cell death in Dictyostelium only in the presence of the DIF-1 polyketide or its metabolites. This identified another element of control to this cell death and perhaps also to c-di-GMP effects in other situations and organisms.

Fluorous photosensitizers enhance photodynamic therapy with perfluorocarbon nanoemulsions

2017 ◽  
Author(s):  
Ellen Sletten ◽  
Rachael A. Day ◽  
Daniel A. Estabrook ◽  
Jessica K. Logan
Keyword(s):  
Cell Death ◽  
Photodynamic Therapy ◽  
Induce Cell Death ◽  
Perfluorocarbon Nanoemulsions

<p>Photodynamic therapy (PDT) requires photosensitizer, light, and oxygen to induce cell death. The majority of efforts to advance PDT focus only on the first two components. Here, we employ perfluorocarbon nanoemulsions to simultaneously deliver oxygen and photosensitizer. We find that the implementation of fluorous soluble photosensitizers enhances the efficacy of PDT. </p>

Inhibition of Autophagy Potentiated Hippocampal Cell Death Induced by Endoplasmic Reticulum Stress and its Activation by Trehalose Failed to be Neuroprotective

2019 ◽  
Vol 16 (1) ◽  
pp. 3-11
Author(s):  
Luisa Halbe ◽  
Abdelhaq Rami
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Er Stress ◽  
Cell Damage ◽  
Protective Mechanism ◽  
Unfolded Proteins ◽  
Neuronal Viability ◽  
Hippocampal Cell ◽  
Trigger Cell Death ◽  
Autophagy Inhibition

Introduction: Endoplasmic reticulum (ER) stress induced the mobilization of two protein breakdown routes, the proteasomal- and autophagy-associated degradation. During ERassociated degradation, unfolded ER proteins are translocated to the cytosol where they are cleaved by the proteasome. When the accumulation of misfolded or unfolded proteins excels the ER capacity, autophagy can be activated in order to undertake the degradative machinery and to attenuate the ER stress. Autophagy is a mechanism by which macromolecules and defective organelles are included in autophagosomes and delivered to lysosomes for degradation and recycling of bioenergetics substrate. Materials and Methods: Autophagy upon ER stress serves initially as a protective mechanism, however when the stress is more pronounced the autophagic response will trigger cell death. Because autophagy could function as a double edged sword in cell viability, we examined the effects autophagy modulation on ER stress-induced cell death in HT22 murine hippocampal neuronal cells. We investigated the effects of both autophagy-inhibition by 3-methyladenine (3-MA) and autophagy-activation by trehalose on ER-stress induced damage in hippocampal HT22 neurons. We evaluated the expression of ER stress- and autophagy-sensors as well as the neuronal viability. Results and Conclusion: Based on our findings, we conclude that under ER-stress conditions, inhibition of autophagy exacerbates cell damage and induction of autophagy by trehalose failed to be neuroprotective.

scholarly journals Transcriptional CDK inhibitors, CYC065 and THZ1 promote Bim-dependent apoptosis in primary and recurrent GBM through cell cycle arrest and Mcl-1 downregulation

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Viktorija Juric ◽  
Lance Hudson ◽  
Joanna Fay ◽  
Cathy E. Richards ◽  
Hanne Jahns ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Cell Cycle Arrest ◽  
Cortical Neurons ◽  
Apoptotic Cell ◽  
Cdk Inhibitors ◽  
Induce Cell Death ◽  
Viability Loss ◽  
Cycle Arrest ◽  
Recurrent Gbm

AbstractActivation of cyclin-dependent kinases (CDKs) contributes to the uncontrolled proliferation of tumour cells. Genomic alterations that lead to the constitutive activation or overexpression of CDKs can support tumourigenesis including glioblastoma (GBM), the most common and aggressive primary brain tumour in adults. The incurability of GBM highlights the need to discover novel and more effective treatment options. Since CDKs 2, 7 and 9 were found to be overexpressed in GBM, we tested the therapeutic efficacy of two CDK inhibitors (CKIs) (CYC065 and THZ1) in a heterogeneous panel of GBM patient-derived cell lines (PDCLs) cultured as gliomaspheres, as preclinically relevant models. CYC065 and THZ1 treatments suppressed invasion and induced viability loss in the majority of gliomaspheres, irrespective of the mutational background of the GBM cases, but spared primary cortical neurons. Viability loss arose from G2/M cell cycle arrest following treatment and subsequent induction of apoptotic cell death. Treatment efficacies and treatment durations required to induce cell death were associated with proliferation velocities, and apoptosis induction correlated with complete abolishment of Mcl-1 expression, a cell cycle-regulated antiapoptotic Bcl-2 family member. GBM models generally appeared highly dependent on Mcl-1 expression for cell survival, as demonstrated by pharmacological Mcl-1 inhibition or depletion of Mcl-1 expression. Further analyses identified CKI-induced Mcl-1 loss as a prerequisite to establish conditions at which the BH3-only protein Bim can efficiently induce apoptosis, with cellular Bim amounts strongly correlating with treatment efficacy. CKIs reduced proliferation and promoted apoptosis also in chick embryo xenograft models of primary and recurrent GBM. Collectively, these studies highlight the potential of these novel CKIs to suppress growth and induce cell death of patient-derived GBM cultures in vitro and in vivo, warranting further clinical investigation.

scholarly journals The RelA hydrolase domain acts as a molecular switch for (p)ppGpp synthesis

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Anurag Kumar Sinha ◽  
Kristoffer Skovbo Winther
Keyword(s):  
Active Sites ◽  
Molecular Switch ◽  
Cell Physiology ◽  
Synthetase Activity ◽  
Wild Type ◽  
Functional Studies ◽  
Loop Region ◽  
A Site ◽  
Trna Binding

AbstractBacteria synthesize guanosine tetra- and penta phosphate (commonly referred to as (p)ppGpp) in response to environmental stresses. (p)ppGpp reprograms cell physiology and is essential for stress survival, virulence and antibiotic tolerance. Proteins of the RSH superfamily (RelA/SpoT Homologues) are ubiquitously distributed and hydrolyze or synthesize (p)ppGpp. Structural studies have suggested that the shift between hydrolysis and synthesis is governed by conformational antagonism between the two active sites in RSHs. RelA proteins of γ-proteobacteria exclusively synthesize (p)ppGpp and encode an inactive pseudo-hydrolase domain. Escherichia coli RelA synthesizes (p)ppGpp in response to amino acid starvation with cognate uncharged tRNA at the ribosomal A-site, however, mechanistic details to the regulation of the enzymatic activity remain elusive. Here, we show a role of the enzymatically inactive hydrolase domain in modulating the activity of the synthetase domain of RelA. Using mutagenesis screening and functional studies, we identify a loop region (residues 114–130) in the hydrolase domain, which controls the synthetase activity. We show that a synthetase-inactive loop mutant of RelA is not affected for tRNA binding, but binds the ribosome less efficiently than wild type RelA. Our data support the model that the hydrolase domain acts as a molecular switch to regulate the synthetase activity.

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