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 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.

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 Posttranslational modification and beyond: interplay between histone deacetylase 6 and heat-shock protein 90

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Ping Liu ◽  
Ji Xiao ◽  
Yiliang Wang ◽  
Xiaowei Song ◽  
Lianzhou Huang ◽  
...  
Keyword(s):  
Protein Stability ◽  
Histone Deacetylase ◽  
Gene Transcription ◽  
Posttranslational Modification ◽  
Current Knowledge ◽  
Heat Shock Protein 90 ◽  
Biological Processes ◽  
Histone Deacetylase 6 ◽  
Post Translational Modification ◽  
Nonhistone Proteins

AbstractPosttranslational modification (PTM) and regulation of protein stability are crucial to various biological processes. Histone deacetylase 6 (HDAC6), a unique histone deacetylase with two functional catalytic domains (DD1 and DD2) and a ZnF-UBP domain (ubiquitin binding domain, BUZ), regulates a number of biological processes, including gene expression, cell motility, immune response, and the degradation of misfolded proteins. In addition to the deacetylation of histones, other nonhistone proteins have been identified as substrates for HDAC6. Hsp90, a molecular chaperone that is a critical modulator of cell signaling, is one of the lysine deacetylase substrates of HDAC6. Intriguingly, as one of the best-characterized regulators of Hsp90 acetylation, HDAC6 is the client protein of Hsp90. In addition to regulating Hsp90 at the post-translational modification level, HDAC6 also regulates Hsp90 at the gene transcription level. HDAC6 mainly regulates the Hsp90-HSF1 complex through the ZnF-UBP domain, thereby promoting the HSF1 entry into the nucleus and activating gene transcription. The mutual interaction between HDAC6 and Hsp90 plays an important role in the regulation of protein stability, cell migration, apoptosis and other functions. Plenty of of studies have indicated that blocking HDAC6/Hsp90 has a vital regulatory role in multifarious diseases, mainly in cancers. Therefore, developing inhibitors or drugs against HDAC6/Hsp90 becomes a promising development direction. Herein, we review the current knowledge on molecular regulatory mechanisms based on the interaction of HDAC6 and Hsp90 and inhibition of HDAC6 and/or Hsp90 in oncogenesis and progression, antiviral and immune-related diseases and other vital biological processes.

scholarly journals The Glycine-Phenylalanine-Rich Region Determines the Specificity of the Yeast Hsp40 Sis1

1999 ◽  
Vol 19 (11) ◽  
pp. 7751-7758 ◽  
Author(s):  
Wei Yan ◽  
Elizabeth A. Craig
Keyword(s):  
Amino Acids ◽  
Molecular Chaperones ◽  
Rich Region ◽  
Critical Determinant ◽  
Unique Region ◽  
Chimeric Genes ◽  
F Region ◽  
Initiation Of Translation ◽  
J Domain ◽  
Essential Function

ABSTRACT Hsp40s are ubiquitous, conserved proteins which function with molecular chaperones of the Hsp70 class. Sis1 is an essential Hsp40 of the cytosol of Saccharomyces cerevisiae, thought to be required for initiation of translation. We carried out a genetic analysis to determine the regions of Sis1 required to perform its key function(s). A C-terminal truncation of Sis1, removing 231 amino acids but retaining the N-terminal 121 amino acids encompassing the J domain and the glycine-phenylalanine-rich (G-F) region, was able to rescue the inviability of a Δsis1 strain. The yeast cytosol contains other Hsp40s, including Ydj1. To determine which regions carried the critical determinants of Sis1 function, we constructed chimeric genes containing portions of SIS1 and YDJ1. A chimera containing the J domain of Sis1 and the G-F region of Ydj1 could not rescue the lethality of the Δsis1 strain. However, a chimera with the J domain of Ydj1 and the G/F region of Sis1 could rescue the strain’s lethality, indicating that the G-F region is a unique region required for the essential function of Sis1. However, a J domain is also required, as mutants expected to cause a disruption of the interaction of the J domain with Hsp70 are inviable. We conclude that the G-F region, previously thought only to be a linker or spacer region between the J domain and C-terminal regions of Hsp40s, is a critical determinant of Sis1 function.

scholarly journals Cord Blood-Based Approach to Assess Candidate Vaccine Adjuvants Designed for Neonates and Infants

Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 95
Author(s):  
Daisuke Tokuhara ◽  
Norikatsu Hikita
Keyword(s):  
Cord Blood ◽  
Protective Immunity ◽  
Current Knowledge ◽  
Current System ◽  
Innate Immune ◽  
Vaccine Adjuvants ◽  
Adult Humans ◽  
Neonates And Infants ◽  
Induced Immunity ◽  
Review Current

Neonates and infants are particularly susceptible to infections, for which outcomes tend to be severe. Vaccination is a key strategy for preventing infectious diseases, but the protective immunity achieved through vaccination typically is weaker in infants than in healthy adults. One possible explanation for the poor acquisition of vaccine-induced immunity in infants is that their innate immune response, represented by toll-like receptors, is immature. The current system for developing pediatric vaccines relies on the confirmation of their safety and effectiveness in studies involving the use of mature animals or adult humans. However, creating vaccines for neonates and infants requires an understanding of their uniquely immature innate immunity. Here we review current knowledge regarding the innate immune system of neonates and infants and challenges in developing vaccine adjuvants for those children through analyses of cord blood.

scholarly journals Meteorite Orbits from Observations by Camera Networks

1983 ◽  
Vol 6 ◽  
pp. 399-404 ◽  
Author(s):  
Ian Halliday ◽  
Arthur A. Griffin ◽  
Alan T. Blackwell
Keyword(s):  
Current Knowledge ◽  
Great Difficulty ◽  
Camera Networks ◽  
Significant Group ◽  
Lost City ◽  
Knowledge Based ◽  
Alternative Approach ◽  
Physically Identical ◽  
Review Current ◽  
Visual Observations

Camera networks for the study of bright fireballs now have a history approaching two decades• It was hoped that the networks would produce a statistically significant group of recovered meteorites with accurate orbits. Due to the great difficulty in locating the meteorites from a photographed event, there are still only three meteorites with orbits determined from suitable photographs; Pribram, Lost City and Innisfree (Ceplecha I96I, McCrosky et al. 1971, Halliday et al. 1978, respectively). Networks do, however, provide an alternative approach to the problem. Instead of determining approximate orbits from visual observations of recovered meteorite falls, it is now preferable to use reliable orbits from the camera networks for fireballs which are believed to have dropped meteorites that could not be located, or, that are believed to have been physically identical to meteorites, although no appreciable mass survived the atmospheric flight. This paper will review current knowledge based on this approach to the problem.

scholarly journals Identification of heat-shock protein 90 beta in Japanese encephalitis virus-induced secretion proteins

2011 ◽  
Vol 92 (12) ◽  
pp. 2803-2809 ◽  
Author(s):  
Chun-Yu Hung ◽  
Meng-Chieh Tsai ◽  
Yi-Ping Wu ◽  
Robert Y. L. Wang
Keyword(s):  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Molecular Chaperones ◽  
Heat Shock Protein 90 ◽  
Rna Replication ◽  
Hsp90 Inhibitor ◽  
Encephalitis Virus ◽  
Virus Infectivity ◽  
Density Fractionation ◽  
Virus Particles

Five host cellular proteins were identified in the secretion medium from Japanese encephalitis virus (JEV)-infected baby hamster kidney-21 (BHK-21) cells, including three molecular chaperones: Hsp70, GRP78 and Hsp90. Hsp90 isoforms were characterized further. Hsp90α was observed to be retained inside the nuclei, whereas Hsp90β associated with virus particles during assembly and was released into the secretion medium upon JEV infection. The association of Hsp90β and viral E protein was demonstrated by using sucrose-density fractionation and Western blot analysis. Moreover, JEV viral RNA replication was not affected by treatment with geldanamycin, an Hsp90 inhibitor, but impaired virus infectivity that was determined by a plaque-forming assay. Our results show that Hsp90β, not Hsp90α, is present in the JEV-induced secretion medium and is required for JEV infectivity in BHK-21 cells.

scholarly journals New trends in botulinum toxin use in dermatology

2018 ◽  
pp. 277-282 ◽  
Author(s):  
Stefania Guida ◽  
Francesca Farnetani ◽  
Steven P. Nisticò ◽  
Caterina Giorgio Mariarosaria ◽  
Graziella Babino ◽  
...  
Keyword(s):  
Botulinum Toxin ◽  
Botulinum Neurotoxin ◽  
Current Knowledge ◽  
Hypertrophic Scars ◽  
Skin Disorders ◽  
Facial Flushing ◽  
Cutaneous Lesions ◽  
Raynaud Phenomenon ◽  
Skin Conditions ◽  
Review Current

Background: Recent studies have highlighted new botulinum neurotoxin (BoNT) applications in the field of dermatology. Objective: To review current knowledge of BoNT use in dermatology. Methods: The literature of the last 5 years has been reviewed. Results: We describe interesting protocols of BoNT treatment for hyperhidrosis (HH), hypertrophic scars and keloids, Raynaud phenomenon, facial flushing, oily skin, psoriasis, Hailey-Hailey disease, and cutaneous lesions like painful lesions and periorbital syringomas. Conclusions: Several skin conditions eligible for BoNT treatment have been described. After the wide application for HH treatment, scars as well as vascular and inflammatory skin disorders, oily skin and cutaneous lesions represent fields of application of BoNT.

scholarly journals Synthetic protocell biology: from reproduction to computation

2007 ◽  
Vol 362 (1486) ◽  
pp. 1727-1739 ◽  
Author(s):  
Ricard V Solé ◽  
Andreea Munteanu ◽  
Carlos Rodriguez-Caso ◽  
Javier Macía
Keyword(s):  
Current Knowledge ◽  
Building Blocks ◽  
Biochemical Networks ◽  
Cellular Structures ◽  
Biological Complexity ◽  
Artificial Cell ◽  
Future Challenges ◽  
Cooperative Dynamics ◽  
The Origin Of Life ◽  
Review Current

Cells are the building blocks of biological complexity. They are complex systems sustained by the coordinated cooperative dynamics of several biochemical networks. Their replication, adaptation and computational features emerge as a consequence of appropriate molecular feedbacks that somehow define what life is. As the last decades have brought the transition from the description-driven biology to the synthesis-driven biology, one great challenge shared by both the fields of bioengineering and the origin of life is to find the appropriate conditions under which living cellular structures can effectively emerge and persist. Here, we review current knowledge (both theoretical and experimental) on possible scenarios of artificial cell design and their future challenges.

scholarly journals Lung Interstitial Macrophages: Past, Present, and Future

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Joey Schyns ◽  
Fabrice Bureau ◽  
Thomas Marichal
Keyword(s):  
Dendritic Cells ◽  
Alveolar Macrophages ◽  
Historical Perspective ◽  
Current Knowledge ◽  
Allergic Airway Inflammation ◽  
Immune Functions ◽  
Immune Mediated ◽  
Future Challenges ◽  
Long Time ◽  
Review Current

For a long time, investigations about the lung myeloid compartment have been mainly limited to the macrophages located within the airways, that is, the well-known alveolar macrophages specialized in recycling of surfactant molecules and removal of debris. However, a growing number of reports have highlighted the complexity of the lung myeloid compartment, which also encompass different subsets of dendritic cells, tissue monocytes, and nonalveolar macrophages, called interstitial macrophages (IM). Recent evidence supports that, in mice, IM perform important immune functions, including the maintenance of lung homeostasis and prevention of immune-mediated allergic airway inflammation. In this article, we describe lung IM from a historical perspective and we review current knowledge on their characteristics, ontogeny, and functions, mostly in rodents. Finally, we emphasize some important future challenges for the field.

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