scholarly journals Molecular Chaperones ofLeishmania: Central Players in Many Stress-Related and -Unrelated Physiological Processes

2015 ◽  
Vol 2015 ◽  
pp. 1-21 ◽  
Author(s):  
Jose M. Requena ◽  
Ana M. Montalvo ◽  
Jorge Fraga
Keyword(s):  
Molecular Chaperones ◽  
Current Knowledge ◽  
Intracellular Localization ◽  
Nutrient Deficiency ◽  
Optimal Growth ◽  
Growth Conditions ◽  
Structural Features ◽  
Insect Vector ◽  
And Shifts ◽  
Shock Proteins

Molecular chaperones are key components in the maintenance of cellular homeostasis and survival, not only during stress but also under optimal growth conditions. Folding of nascent polypeptides is supported by molecular chaperones, which avoid the formation of aggregates by preventing nonspecific interactions and aid, when necessary, the translocation of proteins to their correct intracellular localization. Furthermore, when proteins are damaged, molecular chaperones may also facilitate their refolding or, in the case of irreparable proteins, their removal by the protein degradation machinery of the cell. During their digenetic lifestyle,Leishmaniaparasites encounter and adapt to harsh environmental conditions, such as nutrient deficiency, hypoxia, oxidative stress, changing pH, and shifts in temperature; all these factors are potential triggers of cellular stress. We summarize here our current knowledge on the main types of molecular chaperones inLeishmaniaand their functions. Among them, heat shock proteins play important roles in adaptation and survival of this parasite against temperature changes associated with its passage from the poikilothermic insect vector to the warm-blooded vertebrate host. The study of structural features and the function of chaperones inLeishmaniabiology is providing opportunities (and challenges) for drug discovery and improving of current treatments against leishmaniasis.

scholarly journals Membrane-Associated Heat Shock Proteins in Oncology: From Basic Research to New Theranostic Targets

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1263 ◽  
Author(s):  
Maxim Shevtsov ◽  
Zsolt Balogi ◽  
William Khachatryan ◽  
Huile Gao ◽  
László Vígh ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Molecular Chaperones ◽  
Intracellular Localization ◽  
Large Family ◽  
Basic Research ◽  
Stress Factors ◽  
Small Hsps ◽  
Stress Oxidative ◽  
Shock Proteins

Heat shock proteins (HSPs) constitute a large family of conserved proteins acting as molecular chaperones that play a key role in intracellular protein homeostasis, regulation of apoptosis, and protection from various stress factors (including hypoxia, thermal stress, oxidative stress). Apart from their intracellular localization, members of different HSP families such as small HSPs, HSP40, HSP60, HSP70 and HSP90 have been found to be localized on the plasma membrane of malignantly transformed cells. In the current article, the role of membrane-associated molecular chaperones in normal and tumor cells is comprehensively reviewed with implications of these proteins as plausible targets for cancer therapy and diagnostics.

scholarly journals Multifaceted roles of HEAT SHOCK PROTEIN 90 molecular chaperones in plant development

2020 ◽  
Vol 71 (14) ◽  
pp. 3966-3985 ◽  
Author(s):  
Tereza Tichá ◽  
Despina Samakovli ◽  
Anna Kuchařová ◽  
Tereza Vavrdová ◽  
Jozef Šamaj
Keyword(s):  
Heat Shock ◽  
Plant Development ◽  
Molecular Chaperones ◽  
Current Knowledge ◽  
Heat Shock Protein 90 ◽  
Molecular Networks ◽  
Genetic Perturbations ◽  
Client Proteins ◽  
Developmental Signalling ◽  
Shock Proteins

Abstract HEAT SHOCK PROTEINS 90 (HSP90s) are molecular chaperones that mediate correct folding and stability of many client proteins. These chaperones act as master molecular hubs involved in multiple aspects of cellular and developmental signalling in diverse organisms. Moreover, environmental and genetic perturbations affect both HSP90s and their clients, leading to alterations of molecular networks determining respectively plant phenotypes and genotypes and contributing to a broad phenotypic plasticity. Although HSP90 interaction networks affecting the genetic basis of phenotypic variation and diversity have been thoroughly studied in animals, such studies are just starting to emerge in plants. Here, we summarize current knowledge and discuss HSP90 network functions in plant development and cellular homeostasis.

The universe of Hsp90

2012 ◽  
Vol 3 (1) ◽  
pp. 79-97 ◽  
Author(s):  
Marta Stankiewicz ◽  
Matthias P. Mayer
Keyword(s):  
Posttranslational Modifications ◽  
Optimal Growth ◽  
Growth Conditions ◽  
Special Role ◽  
Regulatory Circuits ◽  
Health And Disease ◽  
Client Proteins ◽  
Essential Function ◽  
Shock Proteins

AbstractMolecular chaperones are key components in the maintenance of cellular homeostasis and survival, not only during stress but also under optimal growth conditions. Among the ATP-dependent chaperones, heat shock proteins (Hsp90) proteins play a special role. While Hsp90s can interact with unfolded and misfolded proteins, their main (and in eukaryotic cells essential) function appears to involve interactions with a limited number of protein clients at late steps of maturation or in “alter-native” conformations for regulating their stability and activity. Because Hsp90 clients are hubs of diverse signaling networks and participate in nearly every cellular function, Hsp90s interconnect many regulatory circuits and link them to environmental impacts. The availability and activity of Hsp90 may thus influence complex physiological and pathophysiological processes, such as differentiation, development, aging, cancer, neurodegeneration, and infectious diseases. Furthermore, through homeostatic effects on differentiation and development, Hsp90s act as capacitors of phenotypic evolution. In this review, we discuss recent insights in the structure and chaperone cycle of Hsp90s, the mechanisms underlying Hsp90 binding to clients, and potential reasons why client proteins specifically require the assistance of Hsp90s. Moreover, the current views on Hsp90-cochaperone interactions and regulation of Hsp90 proteins via posttranslational modifications are summarized. The second half of this article is devoted to the role of Hsp90 proteins in health and disease, aging, and evolution.

Integrating the dynamics of yield traits in rice in response to environmental changes

2019 ◽  
Vol 71 (2) ◽  
pp. 490-506 ◽  
Author(s):  
Kamlesh Kant Nutan ◽  
Ray Singh Rathore ◽  
Amit Kumar Tripathi ◽  
Manjari Mishra ◽  
Ashwani Pareek ◽  
...  
Keyword(s):  
Plant Architecture ◽  
Molecular Mechanisms ◽  
Environmental Changes ◽  
Crop Yields ◽  
Current Knowledge ◽  
Global Climate ◽  
Optimal Growth ◽  
Growth Conditions ◽  
Yield Traits ◽  
Comprehensive Understanding

Abstract Reductions in crop yields as a consequence of global climate change threaten worldwide food security. It is therefore imperative to develop high-yielding crop plants that show sustainable production under stress conditions. In order to achieve this aim through breeding or genetic engineering, it is crucial to have a complete and comprehensive understanding of the molecular basis of plant architecture and the regulation of its sub-components that contribute to yield under stress. Rice is one of the most widely consumed crops and is adversely affected by abiotic stresses such as drought and salinity. Using it as a model system, in this review we present a summary of our current knowledge of the physiological and molecular mechanisms that determine yield traits in rice under optimal growth conditions and under conditions of environmental stress. Based on physiological functioning, we also consider the best possible combination of genes that may improve grain yield under optimal as well as environmentally stressed conditions. The principles that we present here for rice will also be useful for similar studies in other grain crops.

Chaperones for proper androgen action – a plethora of assistance to androgen receptor function

2012 ◽  
Vol 11 (1) ◽  
Author(s):  
Wiebke Hessenkemper ◽  
Aria Baniahmad
Keyword(s):  
Androgen Receptor ◽  
Molecular Chaperones ◽  
Glucocorticoid Receptors ◽  
Intracellular Localization ◽  
Progesterone Receptors ◽  
Normal Prostate ◽  
Androgen Action ◽  
Age Related ◽  
Shock Proteins ◽  
Prostate Growth

AbstractThe androgen receptor (AR) plays a major role for normal prostate growth and also promotes the development and progression of prostate cancer (PCa). PCa, an important age-related disease, is one of the most commonly diagnosed cancers and the second leading cause of cancer mortality for men in Western countries. AR function and activity are regulated by molecular chaperones. The AR belongs to the steroid hormone receptor (SHR) family and can be activated by androgens such as dihydrotestosterone. SHRs are ligand-dependent transcription factors that are predominantly localized in the cytoplasm in the absence of their appropriate ligand. Upon hormone binding, translocation to the nucleus occurs as shown for glucocorticoid receptors, mineralocorticoid receptors, or the AR, while others, such as estrogen and progesterone receptors, are mainly nuclear. Importantly, the newly synthesized and unliganded receptors bind stepwise with chaperones then being associated in a dynamic chaperone heterocomplex, including heat shock proteins. It emerges that chaperones are very important, not only in the proper folding of the AR but they are also involved in receptor stability, intracellular localization and androgen-controlled transcription. Accordingly, chaperones may be interesting future targets for PCa treatment. In this review we will summarize the involvement of chaperones controlling AR activity.

scholarly journals The Hsp90 chaperone system from the African trypanosome, Trypanosoma brucei

2021 ◽  
Author(s):  
Aileen Boshoff ◽  
Miebaka Jamabo ◽  
Stephen J Bentley ◽  
Paula Macucule-Tinga ◽  
Adrienne Edkins
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Trypanosoma Brucei ◽  
Molecular Chaperones ◽  
Sub Saharan Africa ◽  
Mammalian Host ◽  
Insect Vector ◽  
Single Chromosome ◽  
African Trypanosome ◽  
Shock Proteins

African Trypanosomiasis is a neglected tropical disease caused by Trypanosoma brucei ( T. brucei ) and is spread by the tsetse fly in sub-Saharan Africa. The disease is fatal if left untreated and the currently approved drugs for treatment are toxic and difficult to administer. The trypanosome must survive in the insect vector and its mammalian host, and to adapt to these different conditions, the parasite relies on molecular chaperones called heat shock proteins. Heat shock proteins mediate the folding of newly synthesized proteins as well as prevent misfolding of proteins under normal conditions and during stressful conditions. Heat shock protein 90 (Hsp90) is one of the major molecular chaperones of the stress response at the cellular level. It functions with other chaperones and co-chaperones and inhibition of its interactions is being explored as a potential therapeutic target for numerous diseases. This study provides an in-silico overview of Hsp90 and its co-chaperones in both T. brucei brucei and T. brucei gambiense in relation to human and other kinetoplastid parasites . The evolutionary, functional, and structural analyses of Hsp90 were also shown. The updated information on Hsp90 and its co-chaperones from recently published proteomics on T. brucei was examined for the different life cycle stages and subcellular localisations. The results show a difference between T. b. brucei and T. b. gambiense with T. b. brucei encoding 12 putative Hsp90 genes, 10 of which are cytosolic and located on a single chromosome while T. gambiense encodes 5 Hsp90 genes, 3 of which are located in the cytosol. Eight putative co-chaperones were identified in this study, 6 TPR-containing and 2 non-TPR-containing co-chaperones. This study provides an updated context for studying the biology of the African trypanosome and evaluating Hsp90 and its interactions as potential drug targets.

scholarly journals Molecular Cochaperones: Tumor Growth and Cancer Treatment

Scientifica ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Stuart K. Calderwood
Keyword(s):  
Molecular Chaperones ◽  
Posttranslational Modification ◽  
Benign Tumor ◽  
Current Knowledge ◽  
Intracellular Localization ◽  
Heat Shock Protein 90 ◽  
Mutant Proteins ◽  
J Domain ◽  
Pharmaceutical Agents ◽  
Review Current

Molecular chaperones play important roles in all cellular organisms by maintaining the proteome in an optimally folded state. They appear to be at a premium in cancer cells whose evolution along the malignant pathways requires the fostering of cohorts of mutant proteins that are employed to overcome tumor suppressive regulation. To function at significant rates in cells, HSPs interact with cochaperones, proteins that assist in catalyzing individual steps in molecular chaperoning as well as in posttranslational modification and intracellular localization. We review current knowledge regarding the roles of chaperones such as heat shock protein 90 (Hsp90) and Hsp70 and their cochaperones in cancer. Cochaperones are potential targets for cancer therapy in themselves and can be used to assess the likely prognosis of individual malignancies. Hsp70 cochaperones Bag1, Bag3, and Hop play significant roles in the etiology of some cancers as do Hsp90 cochaperones Aha1, p23, Cdc37, and FKBP1. Others such as the J domain protein family, HspBP1, TTC4, and FKBPL appear to be associated with more benign tumor phenotypes. The key importance of cochaperones for many pathways of protein folding in cancer suggests high promise for the future development of novel pharmaceutical agents.

scholarly journals Spermidine Acetyltransferase Is Required To Prevent Spermidine Toxicity at Low Temperatures in Escherichia coli

2000 ◽  
Vol 182 (19) ◽  
pp. 5373-5380 ◽  
Author(s):  
Kornvika Limsuwun ◽  
Pamela G. Jones
Keyword(s):  
Escherichia Coli ◽  
Protein Synthesis ◽  
Low Temperature ◽  
Low Temperatures ◽  
Cold Shock ◽  
Optimal Growth ◽  
Growth Conditions ◽  
Cellular Growth ◽  
Ribosome Inactivation ◽  
Shock Proteins

ABSTRACT Polyamines are required for optimal growth in most cells; however, polyamine accumulation leads to inhibition of cellular growth. To reduce intracellular polyamine levels, spermidine is monoacetylated in both prokaryotes and eukaryotes. In Escherichia coli, thespeG gene encodes the spermidine acetyltransferase, which transfers the acetyl group to either the N-1 or N-8 position. In addition to polyamine accumulation, stress conditions, such as cold shock, cause an increase in the level of spermidine acetylation, suggesting an adaptive role for reduced polyamine levels under stressful growth conditions. The effect of spermidine accumulation on the growth of E. coli at low temperature was examined using a speG mutant. At 37°C, growth of the speGmutant was normal in the presence of 0.5 or 1 mM spermidine. However, following a shift to 7°C, the addition of 0.5 or 1 mM spermidine resulted in inhibition of cellular growth or cell lysis, respectively. Furthermore, at 7°C, spermidine accumulation resulted in a decrease in total protein synthesis accompanied by an increase in the synthesis of the major cold shock proteins CspA, CspB, and CspG. However, the addition of 50 mM Mg2+ restored growth and protein synthesis in the presence of 0.5 mM spermidine. The results indicate that the level of spermidine acetylation increases at low temperature to prevent spermidine toxicity. The data suggest that the excess spermidine replaces the ribosome-bound Mg2+, resulting in ribosome inactivation at low temperatures.

scholarly journals Isolation of a gene required for programmed initiation of development by Aspergillus nidulans.

1992 ◽  
Vol 12 (9) ◽  
pp. 3827-3833 ◽  
Author(s):  
T H Adams ◽  
W A Hide ◽  
L N Yager ◽  
B N Lee
Keyword(s):  
Life Cycle ◽  
Aspergillus Nidulans ◽  
Optimal Growth ◽  
Growth Conditions ◽  
Nutrient Deprivation ◽  
Deletion Mutants ◽  
Wild Type ◽  
Microbial Development ◽  
Type Strains ◽  
Posttranscriptional Level

In contrast to many other cases in microbial development, Aspergillus nidulans conidiophore production initiates primarily as a programmed part of the life cycle rather than as a response to nutrient deprivation. Mutations in the acoD locus result in "fluffy" colonies that appear to grow faster than the wild type and proliferate as undifferentiated masses of vegetative cells. We show that unlike wild-type strains, acoD deletion mutants are unable to make conidiophores under optimal growth conditions but can be induced to conidiate when growth is nutritionally limited. The requirement for acoD in conidiophore development occurs prior to activation of brlA, a primary regulator of development. The acoD transcript is present both in vegetative hyphae prior to developmental induction and in developing cultures. However, the effects of acoD mutations are detectable only after developmental induction. We propose that acoD activity is primarily controlled at the posttranscriptional level and that it is required to direct developmentally specific changes that bring about growth inhibition and activation of brlA expression to result in conidiophore development.

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