Special Issue "Cellular Stress Response"

Guest Editor
Dr. Alex Almasan
Department of Cancer Biology, Bridge appointment with Department of Radiation Oncology, Taussig Cancer Institute, Lerner Research Institute / NB40, 9500 Euclid Avenue, Cleveland, OH 44195, USA
Website: http://www.lerner.ccf.org/cancerbio/almasan/
E-Mail: almasaa@ccf.org
Interests: apoptosis; autophagy; cancer (leukemia and prostate); cell death; cell cycle; DNA damage and repair

Dear Colleagues,

Cells are constantly subjected to various forms of endogenous and exogenous stress that shapes their existence. How they respond to it depends on exogenous factors and their ability to handle the stress to which they are exposed.   Examples of cellular stress are the DNA damage caused by radiation, chemotherapy, hypoxia, oncogene activation; these will ultimately lead to transient or permanent (senescence) growth arrest, or if the damage is severe, death that ultimately eliminates the damaged cells . Whether cells mount a protective response or succumb to death depends to a large extent on the nature and duration of the stress and the particular cell type. How such cellular stress leads to activation of pro-survival molecules that may activate repair of DNA damage in the nucleus or in the cytoplasm by autophagy (see dedicated special issue) and/or prevent cell death is of considerable interest. Moreover, alternative splicing and the adaptive response are of special interest.

This Special Issue offers an Open Access forum that aims at bringing together a collection of original research and review articles addressing recent developments in the cellular stress response, the signaling pathways that mitigate its biological effects and the ensuing cell proliferation and/or survival outcomes.

Dr. Alex Almasan
Guest Editor

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed Open Access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. For the first couple of issues the Article Processing Charge (APC) will be waived for well-prepared manuscripts. English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.

• Adaptation
• Autophagy
• Cell cycle arrest
• Cellular stress
• DNA repair
• Genotoxic stress
• Hypoxia
• Oncogene activation
• Oxidative stress
• Programmed cell death
• Senescence

Type of Paper: Review
Title: P53-dependent and -independent Nucleolar Stress Responses
Author: Mikael S. Lindström
Affiliation: Department of Oncology-Pathology, Karolinska Institutet, SE-17176 Stockholm, Sweden; E-Mail: Mikael.Lindstrom@ki.se
Abstract: A hallmark of cancer is increased cell growth and proliferation. Ribosome biogenesis that takes place in the nucleolus is in this context a critical cellular process. A variety of abnormal metabolic conditions or cytotoxic compounds can cause disturbances in ribosome biogenesis. It is now established that disruption of the nucleolus triggers a p53-dependent cellular stress response known as nucleolar stress or ribosomal stress. Nucleolar stress activates signaling pathways that may lead to cell cycle arrest, apoptosis, differentiation or senescence. These pathways will be described and discussed in detail.

Type of Paper: Review
Title: Virus-Heat Shock Protein Interaction and a Novel Axis for Innate Antiviral Immunity
Authors: Mi Young Kim and Michael Oglesbee
Affiliation: The Ohio State University, Department of Veterinary Biosciences, 1925 Coffer Road, Columbus, OH 43210, USA; E-Mail: Michael.Oglesbee@cvm.osu.edu
Abstract: Virus infections induce heat shock proteins that in turn enhance virus gene expression, a phenomenon that is particularly well characterized for the major inducible 70 kDa heat shock protein (hsp70). But hsp70 is also readily induced by fever, a phylogenetically conserved response to microbial infections, and when released from cells, hsp70 can stimulate innate immune responses through toll like receptors 2 and 4 (TLR2 and 4). This review examines how the virus-hsp70 relationship can lead to host protective innate antiviral immunity, and the importance of hsp70 dependent stimulation of virus gene expression in this host response. Beginning with the well-characterized measles virus-hsp70 relationship and the mouse model of neuronal infection in brain, we examine data indicating that the innate immune response is not driven by intracellular sensors of pathogen associated molecular patterns, but rather by extracellular ligands signaling through TLR2 and 4. Specifically, we address the relationship between virus gene expression, extracellular release of hsp70 (as a damage associated molecular pattern), and hsp70-mediated induction of antigen presentation and type 1 interferons in uninfected macrophages as a novel axis of antiviral immunity. New data is introduced that examines the more broad relevance of this protective mechanism using vesicular stomatitis virus, and a review of the literature is presented that supports the probable relevance to both RNA and DNA viruses and for infections both within and outside of the central nervous system.

Type of Paper: Article
Title: Cellular Stress Following Water Deprivation in the Model Legume Lotus japonicus: A Transcriptomics Approach
Authors: Marco Betti, Carmen Pérez-Delgado, Margarita García-Calderón and Antonio J. Márquez
Affiliation: Departamento de Bioquímica Vegetal y Biología Molecular, Facultad de Química, Universidad de Sevilla, Calle Profesor García González, 1, 41012-Sevilla, Spain; E-Mail: mbetti@us.es
Abstract: Drought stress is one of the most important factors that limits plant productivity worldwide. In order to cope with water deprivation, plants have adapted several strategies that include major changes in gene expression. In this paper, the response to drought stress of the model legume Lotus japonicus was characterised using DNA chips. Several cellular metabolisms were elicited by the stress conditions imposed and included the modulation of genes involved in the response to oxidative stress, cell wall metabolism, stress perception and signalling as well as a number of transcription factors. Transcriptomic data were analyzed with a particular focus on genes that were involved in the cellular stress response. Finally, drought-stress transcriptomes were obtained from plants grown either under CO2-enriched or low CO2 atmosphere. This permitted the identification of genes that were elicited by drought only in the presence of high carbon or under active photorespiratory conditions.

Type of Paper: Review
Title: Stress Response Pathways in Ameloblasts: Implications for Amelogenesis and Dental Fluorosis
Authors: Megan L. Sierant and John D. Bartlett*
Affiliation: Department of Cytokine Biology, Forsyth Institute; 245 First St., Cambridge, MA, 02142 & Harvard School of Dental Medicine, 188 Longwood Ave, Boston, MA, 02115, USA; E-Mails: msierant@forsyth.org (M.L.S.); jbartlett@forsyth.org (J.D.B.)
Abstract: Human enamel development of the permanent teeth takes place during childhood and stresses encountered during this period can have lasting effects on the appearance and structural integrity of the enamel. One of the most common examples of this is the development of dental fluorosis after childhood exposure to excess fluoride, a chemical agent used to increase enamel hardness and prevent dental caries. Currently the molecular mechanism responsible for dental fluorosis remains unknown; however, recent work suggests dental fluorosis may be the result of activated stress response pathways in ameloblasts during the development of permanent teeth. Using fluorosis as an example, the role of stress response pathways during enamel maturation is discussed.

Type of Paper: Review
Title: Activating the Unfolded Protein Response without any Unfolded Proteins?
Author: Erik L. Snapp
Affiliation: Albert Einstein College of Medicine, Jack and Pearl Resnick Campus, 1300 Morris Park Avenue, Forchheimer Building, Room 640, Bronx, NY 10461, USA; E-Mail: erik-lee.snapp@einstein.yu.edu
Abstract: The endoplasmic reticulum (ER) plays numerous roles in eukaryotic cells including calcium regulation, lipid synthesis, and secretory protein biogenesis. To prevent and resolve accumulation of misfolded secretory proteins in the ER Cells have evolved integral membrane sensors that perform the Unfolded Protein Response (UPR). The sensors, Ire1p in yeast and IRE1, ATF6, and PERK in metazoans, associate with the luminal ER chaperone BiP during homeostasis and BiP is somehow released as unfolded secretory proteins accumulate and the sensors activate. Mechanisms of activation and attenuation of the UPR sensors remains poorly understood. A growing body of data support a model in which Ire1p, and potentially IRE1 and PERK, directly bind unfolded proteins as part of the activation process. However, evidence for an unfolded protein-independent mechanism has recently emerged, suggesting that the UPR can be activated multiple distinct stimuli and unfolded secretory proteins represent a single facet of a more global ER homeostatic response.

Type of Paper: Review
Title: IAPs in Adaptive Response to Cellular Stress
Authors: Stéphanie Plenchette, Arthur Marivin, Jean Berthelet and Laurence Dubrez
Affiliations: ¹ Institut National de la Santé et de la Recherche Médicale (Inserm) UMR866, Dijon, F-21079, France
² Université de Bourgogne, Institut Fédératif de Recherche (IFR) 100, Dijon, F-21079, France
³ Ecole Pratique des hautes études (EPHE), Dijon, F-21079, France; E-Mail: ldubrez@u-bourgogne.fr
Abstract: Cells are constantly exposed to endogenous and exogenous cellular injuries. They cope with stressful stimulus by adapting their metabolism and activating several "guardian molecules". These pro-survival factorsprevent cell death, protect essential cell constituents, and possibly repair cellular damages. The Inhibitor of APoptosis (IAPs) proteins display both anti-apoptotic and pro-survival properties and their expression can be induced by a variety of cellular stresses such as hypoxia, endoplasmic reticular stress and DNA damage. Thus, the IAPs can confer tolerance to cellular stress. This review will present the anti-apoptotic and survival functions of the IAPs and their role in adaptive response to cellular stress. The involvement of the IAPs in human physiology and diseases in connection with a breakdown of cellular homeostasis will be discussed.

Type of Paper: Review
Title: Oxidative Stress Response, Aging and Technological Performance in Wine Yeasts
Authors: Agustín Aranda, Esther Gamero, Rocío Gómez-Pastor, Helena Orozco and Emilia Matallana
Affiliation: Departamento de Biotecnología, Instituto de Agroquímica y Tecnología de Alimentos, CSIC, and Departament de Bioquímica i Biologia Molecular, Universitat de València, Avda Agustín Escardino 7, 46980 Paterna, Valencia, Spain; E-Mail: arandaa@iata.csic.es (A.A.); emilia.matallana@uv.es (E.M.)
Abstract: Wine strains of Saccharomyces cerevisiae, as all cells, have developed molecular mechanisms to respond and adapt to stress conditions, common challenges which gain particular relevance for the technological performance of these microorganisms. The efficiency of such stress responses determines cell survival and relies on a complex network of protective molecules, enzymatic activities and signaling pathways, highly conserved among eukaryotes, as also are the consequences of severe stress on cell integrity and the mechanisms of aging and cell death. Recent advances in the knowledge of connections between oxidative stress, life span and industrial fitness of natural wine yeast strains in laboratory conditions and during the different stages of their industrial usage will be reviewed and discussed.