p53 at the Crossroads Between Stress Response Signaling and Tumorigenesis: From Molecular Mechanisms to Therapeutic Opportunities

APETALA2/ETHYLENE RESPONSIVE FACTOR (AP2/ERF) transcription factors play important roles in plant development and stress response. Although AP2/ERF genes have been extensively investigated in model plants such as Arabidopsis thaliana, little is known about their role in biotic stress response in perennial fruit tree crops such as apple (Malus × domestica). Here, we investigated the role of MdERF100 in powdery mildew resistance in apple. MdERF100 localized to the nucleus but showed no transcriptional activation activity. The heterologous expression of MdERF100 in Arabidopsis not only enhanced powdery mildew resistance but also increased reactive oxygen species (ROS) accumulation and cell death. Furthermore, MdERF100-overexpressing Arabidopsis plants exhibited differential expressions of genes involved in jasmonic acid (JA) and salicylic acid (SA) signaling when infected with the powdery mildew pathogen. Additionally, yeast two-hybrid and bimolecular fluorescence complementation assays confirmed that MdERF100 physically interacts with the basic helix–loop–helix (bHLH) protein MdbHLH92. These results suggest that MdERF100 mediates powdery mildew resistance by regulating the JA and SA signaling pathways, and MdbHLH92 is involved in plant defense against powdery mildew. Overall, this study enhances our understanding of the role of MdERF genes in disease resistance, and provides novel insights into the molecular mechanisms of powdery mildew resistance in apple.

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Impact of Carcinogenic Chromium on the Cellular Response to Proteotoxic Stress

International Journal of Molecular Sciences ◽

10.3390/ijms20194901 ◽

2019 ◽

Vol 20 (19) ◽

pp. 4901 ◽

Cited By ~ 6

Author(s):

Leonardo M. R. Ferreira ◽

Teresa Cunha-Oliveira ◽

Margarida C. Sobral ◽

Patrícia L. Abreu ◽

Maria Carmen Alpoim ◽

...

Keyword(s):

Stress Response ◽

Health Effects ◽

Cellular Response ◽

Molecular Mechanisms ◽

Critical Role ◽

Chemical Properties ◽

Adverse Health Effects ◽

Proteotoxic Stress ◽

Adverse Health ◽

The Impact

Worldwide, several million workers are employed in the various chromium (Cr) industries. These workers may suffer from a variety of adverse health effects produced by dusts, mists and fumes containing Cr in the hexavalent oxidation state, Cr(VI). Of major importance, occupational exposure to Cr(VI) compounds has been firmly associated with the development of lung cancer. Counterintuitively, Cr(VI) is mostly unreactive towards most biomolecules, including nucleic acids. However, its intracellular reduction produces several species that react extensively with biomolecules. The diversity and chemical versatility of these species add great complexity to the study of the molecular mechanisms underlying Cr(VI) toxicity and carcinogenicity. As a consequence, these mechanisms are still poorly understood, in spite of intensive research efforts. Here, we discuss the impact of Cr(VI) on the stress response—an intricate cellular system against proteotoxic stress which is increasingly viewed as playing a critical role in carcinogenesis. This discussion is preceded by information regarding applications, chemical properties and adverse health effects of Cr(VI). A summary of our current understanding of cancer initiation, promotion and progression is also provided, followed by a brief description of the stress response and its links to cancer and by an overview of potential molecular mechanisms of Cr(VI) carcinogenicity.

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RNA sequencing reveals metabolic and regulatory changes leading to more robust fermentation performance during short-term adaptation of Saccharomyces cerevisiae to lignocellulosic inhibitors

Biotechnology for Biofuels ◽

10.1186/s13068-021-02049-y ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Marlous van Dijk ◽

Peter Rugbjerg ◽

Yvonne Nygård ◽

Lisbeth Olsson

Keyword(s):

Saccharomyces Cerevisiae ◽

Stress Response ◽

Rna Sequencing ◽

Molecular Mechanisms ◽

Lignocellulosic Hydrolysate ◽

Short Term ◽

Down Regulation ◽

Time Resolved ◽

Second Generation Bioethanol ◽

Short Term Adaptation

Abstract Background The limited tolerance of Saccharomyces cerevisiae to inhibitors is a major challenge in second-generation bioethanol production, and our understanding of the molecular mechanisms providing tolerance to inhibitor-rich lignocellulosic hydrolysates is incomplete. Short-term adaptation of the yeast in the presence of dilute hydrolysate can improve its robustness and productivity during subsequent fermentation. Results We utilized RNA sequencing to investigate differential gene expression in the industrial yeast strain CR01 during short-term adaptation, mimicking industrial conditions for cell propagation. In this first transcriptomic study of short-term adaption of S. cerevisiae to lignocellulosic hydrolysate, we found that cultures respond by fine-tuned up- and down-regulation of a subset of general stress response genes. Furthermore, time-resolved RNA sequencing allowed for identification of genes that were differentially expressed at 2 or more sampling points, revealing the importance of oxidative stress response, thiamin and biotin biosynthesis. furan-aldehyde reductases and specific drug:H+ antiporters, as well as the down-regulation of certain transporter genes. Conclusions These findings provide a better understanding of the molecular mechanisms governing short-term adaptation of S. cerevisiae to lignocellulosic hydrolysate, and suggest new genetic targets for improving fermentation robustness.

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Physiological and transcriptomic analyses reveal the mechanisms underlying the salt tolerance of Zoysia japonica Steud.

10.21203/rs.2.16313/v3 ◽

2020 ◽

Author(s):

Jingjing Wang ◽

Cong An ◽

Hailin Guo ◽

Xiangyang Yang ◽

Jingbo Chen ◽

...

Keyword(s):

Signal Transduction ◽

Salt Stress ◽

Stress Response ◽

Salt Tolerance ◽

Molecular Mechanisms ◽

Salt Tolerant ◽

Zoysia Japonica ◽

Salt Stress Response ◽

Leaves And Roots ◽

Time Point

Abstract Background: Areas with saline soils are sparsely populated and have fragile ecosystems, which severely restricts the sustainable development of local economies. Zoysia grasses are recognized as excellent warm-season turfgrasses worldwide, with high salt tolerance and superior growth in saline-alkali soils. However, the mechanism underlying the salt tolerance of Zoysia species remains unknown. Results: The phenotypic and physiological responses of two contrasting materials, Zoysia japonica Steud. Z004 (salt sensitive) and Z011 (salt tolerant) in response to salt stress were studied. The results show that Z011 was more salt tolerant than was Z004, with the former presenting greater K+/Na+ ratios in both its leaves and roots. To study the molecular mechanisms underlying salt tolerance further, we compared the transcriptomes of the two materials at different time points (0 h, 1 h, 24 h, and 72 h) and from different tissues (leaves and roots) under salt treatment. The 24-h time point and the roots might make significant contributions to the salt tolerance. Moreover, GO and KEGG analyses of different comparisons revealed that the key DEGs participating in the salt-stress response belonged to the hormone pathway, various TF families and the DUF family. Conclusions: Z011 may have improved salt tolerance by reducing Na+ transport from the roots to the leaves, increasing K+ absorption in the roots and reducing K+ secretion from the leaves to maintain a significantly greater K+/Na+ ratio. Twenty-four hours might be a relatively important time point for the salt-stress response of zoysiagrass. The auxin signal transduction family, ABA signal transduction family, WRKY TF family and bHLH TF family may be the most important families in Zoysia salt-stress regulation. This study provides fundamental information concerning the salt-stress response of Zoysia and improves the understanding of molecular mechanisms in salt-tolerant plants.

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The C. elegans Hypertonic Stress Response: Big Insights from Shrinking Worms

Cellular Physiology and Biochemistry ◽

10.33594/000000332 ◽

2020 ◽

Vol 55 (S1) ◽

pp. 89-105

Keyword(s):

Stress Response ◽

Cell Volume ◽

Molecular Mechanisms ◽

Model Organism ◽

Future Research ◽

Transcriptional Level ◽

Molecular Signaling ◽

Hypertonic Stress ◽

Macromolecular Assemblies ◽

C Elegans

Cell volume is one of the most aggressively defended physiological set points in biology. Changes in intracellular ion and water concentrations, which are induced by changes in metabolism or environmental exposures, disrupt protein folding, enzymatic activity, and macromolecular assemblies. To counter these challenges, cells and organisms have evolved multifaceted, evolutionarily conserved molecular mechanisms to restore cell volume and repair stress induced damage. However, many unanswered questions remain regarding the nature of cell volume 'sensing' as well as the molecular signaling pathways involved in activating physiological response mechanisms. Unbiased genetic screening in the model organism C. elegans is providing new and unexpected insights into these questions, particularly questions relating to the hypertonic stress response (HTSR) pathway. One surprising characteristic of the HTSR pathway in C. elegans is that it is under strong negative regulation by proteins involved in protein homeostasis and the extracellular matrix (ECM). The role of the ECM in particular highlights the importance of studying the HTSR in the context of a live organism where native ECM-tissue associations are preserved. A second novel and recently discovered characteristic is that the HTSR is regulated at the post-transcriptional level. The goal of this review is to describe these discoveries, to provide context for their implications, and to raise outstanding questions to guide future research.

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Recent understanding on molecular mechanisms of plant abiotic stress response and tolerance.

Molecular breeding in wheat, maize and sorghum: strategies for improving abiotic stress tolerance and yield ◽

10.1079/9781789245431.0001 ◽

2021 ◽

pp. 1-23

Author(s):

Geoffrey Onaga ◽

Kerstin Wydra

Keyword(s):

Abiotic Stress ◽

Stress Response ◽

Abiotic Stresses ◽

Crop Production ◽

Molecular Mechanisms ◽

Abiotic Stress Response ◽

Molecular Components ◽

Plant Abiotic Stress

Abstract This chapter provides an overview of the recent significant perspectives on molecules involved in response and tolerance to drought and salinity, the 2 major abiotic stresses affecting crop production, and highlights major molecular components identified in major cereals.

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Functional crosstalk between myeloid Foxo1–β-catenin axis and Hedgehog/Gli1 signaling in oxidative stress response

Cell Death and Differentiation ◽

10.1038/s41418-020-00695-7 ◽

2020 ◽

Author(s):

Changyong Li ◽

Mingwei Sheng ◽

Yuanbang Lin ◽

Dongwei Xu ◽

Yizhu Tian ◽

...

Keyword(s):

Oxidative Stress ◽

Stress Response ◽

Molecular Mechanisms ◽

Ischemia Reperfusion Injury ◽

Cell Metabolism ◽

Ischemia Reperfusion ◽

Neutrophil Infiltration ◽

Oxidative Stress Response ◽

Proinflammatory Mediators ◽

Hepatocellular Damage

AbstractFoxo1 transcription factor is an evolutionarily conserved regulator of cell metabolism, oxidative stress, inflammation, and apoptosis. Activation of Hedgehog/Gli signaling is known to regulate cell growth, differentiation, and immune function. However, the molecular mechanisms by which interactive cell signaling networks restrain oxidative stress response and necroptosis are still poorly understood. Here, we report that myeloid-specific Foxo1 knockout (Foxo1M-KO) mice were resistant to oxidative stress-induced hepatocellular damage with reduced macrophage/neutrophil infiltration, and proinflammatory mediators in liver ischemia/reperfusion injury (IRI). Foxo1M-KO enhanced β-catenin-mediated Gli1/Snail activity, and reduced receptor-interacting protein kinase 3 (RIPK3) and NIMA-related kinase 7 (NEK7)/NLRP3 expression in IR-stressed livers. Disruption of Gli1 in Foxo1M-KO livers deteriorated liver function, diminished Snail, and augmented RIPK3 and NEK7/NLRP3. Mechanistically, macrophage Foxo1 and β-catenin colocalized in the nucleus, whereby the Foxo1 competed with T-cell factor (TCF) for interaction with β-catenin under inflammatory conditions. Disruption of the Foxo1–β-catenin axis by Foxo1 deletion enhanced β-catenin/TCF binding, activated Gli1/Snail signaling, leading to inhibited RIPK3 and NEK7/NLRP3. Furthermore, macrophage Gli1 or Snail knockout activated RIPK3 and increased hepatocyte necroptosis, while macrophage RIPK3 ablation diminished NEK7/NLRP3-driven inflammatory response. Our findings underscore a novel molecular mechanism of the myeloid Foxo1–β-catenin axis in regulating Hedgehog/Gli1 function that is key in oxidative stress-induced liver inflammation and necroptosis.

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The coupling of translational control and stress responses

The Journal of Biochemistry ◽

10.1093/jb/mvaa061 ◽

2020 ◽

Vol 168 (2) ◽

pp. 93-102 ◽

Cited By ~ 1

Author(s):

Ryan Houston ◽

Shiori Sekine ◽

Yusuke Sekine

Keyword(s):

Stress Response ◽

Stress Responses ◽

Translational Control ◽

Messenger Rna ◽

Mammalian Cells ◽

Molecular Mechanisms ◽

Translation Rate ◽

Nucleolar Stress ◽

Multistep Process ◽

Aminoacyl Transfer

Abstract The translation of messenger RNA (mRNA) into protein is a multistep process by which genetic information transcribed into an mRNA is decoded to produce a specific polypeptide chain of amino acids. Ribosomes play a central role in translation by coordinately working with various translation regulatory factors and aminoacyl-transfer RNAs. Various stresses attenuate the ribosomal synthesis in the nucleolus as well as the translation rate in the cytosol. To efficiently reallocate cellular energy and resources, mammalian cells are endowed with mechanisms that directly link the suppression of translation-related processes to the activation of stress adaptation programmes. This review focuses on the integrated stress response (ISR) and the nucleolar stress response (NSR) both of which are activated by various stressors and selectively upregulate stress-responsive transcription factors. Emerging findings have delineated the detailed molecular mechanisms of the ISR and NSR and expanded their physiological and pathological significances.

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Cellular and molecular mechanisms of the brain-derived neurotrophic factor in physiological and pathological conditions

Clinical Science ◽

10.1042/cs20160009 ◽

2016 ◽

Vol 131 (2) ◽

pp. 123-138 ◽

Cited By ~ 56

Author(s):

Veronica Begni ◽

Marco Andrea Riva ◽

Annamaria Cattaneo

Keyword(s):

Synaptic Plasticity ◽

Stress Response ◽

Neurotrophic Factor ◽

Molecular Mechanisms ◽

Depressive Disorders ◽

Brain Derived Neurotrophic Factor ◽

Mitogen Activated Protein Kinase ◽

Bdnf Expression ◽

Pathological Conditions ◽

Wide Range

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a key role in the central nervous system, promoting synaptic plasticity, neurogenesis and neuroprotection. The BDNF gene structure is very complex and consists of multiple 5′-non-coding exons, which give rise to differently spliced transcripts, and one coding exon at the 3′-end. These multiple transcripts, together with the complex transcriptional regulatory machinery, lead to a complex and fine regulation of BDNF expression that can be tissue and stimulus specific. BDNF effects are mainly mediated by the high-affinity, tropomyosin-related, kinase B receptor and involve the activation of several downstream cascades, including the mitogen-activated protein kinase, phospholipase C-γ and phosphoinositide-3-kinase pathways. BDNF exerts a wide range of effects on neuronal function, including the modulation of activity-dependent synaptic plasticity and neurogenesis. Importantly, alterations in BDNF expression and function are involved in different brain disorders and represent a major downstream mechanism for stress response, which has important implications in psychiatric diseases, such as major depressive disorders and schizophrenia. In the present review, we have summarized the main features of BDNF in relation to neuronal plasticity, stress response and pathological conditions, and discussed the role of BDNF as a possible target for pharmacological and non-pharmacological treatments in the context of psychiatric illnesses.

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DENR promotes translation reinitiation via ribosome recycling to drive expression of oncogenes including ATF4

Nature Communications ◽

10.1038/s41467-020-18452-2 ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Jonathan Bohlen ◽

Liza Harbrecht ◽

Saioa Blanco ◽

Katharina Clemm von Hohenberg ◽

Kai Fenzl ◽

...

Keyword(s):

Stress Response ◽

Cancer Cells ◽

Strong Correlation ◽

Molecular Mechanisms ◽

Open Reading Frames ◽

Translation Efficiency ◽

Dependent Manner ◽

Translation Factors ◽

Upstream Open Reading Frames ◽

Reading Frames

Abstract Translation efficiency varies considerably between different mRNAs, thereby impacting protein expression. Translation of the stress response master-regulator ATF4 increases upon stress, but the molecular mechanisms are not well understood. We discover here that translation factors DENR, MCTS1 and eIF2D are required to induce ATF4 translation upon stress by promoting translation reinitiation in the ATF4 5′UTR. We find DENR and MCTS1 are only needed for reinitiation after upstream Open Reading Frames (uORFs) containing certain penultimate codons, perhaps because DENR•MCTS1 are needed to evict only certain tRNAs from post-termination 40S ribosomes. This provides a model for how DENR and MCTS1 promote translation reinitiation. Cancer cells, which are exposed to many stresses, require ATF4 for survival and proliferation. We find a strong correlation between DENR•MCTS1 expression and ATF4 activity across cancers. Furthermore, additional oncogenes including a-Raf, c-Raf and Cdk4 have long uORFs and are translated in a DENR•MCTS1 dependent manner.

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