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Biomolecules, Volume 5, Issue 2 (June 2015), Pages 282-1194

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Open AccessArticle A Microplate Growth Inhibition Assay for Screening Bacteriocins against Listeria monocytogenes to Differentiate Their Mode-of-Action
Biomolecules 2015, 5(2), 1178-1194; https://doi.org/10.3390/biom5021178
Received: 6 March 2015 / Revised: 26 May 2015 / Accepted: 4 June 2015 / Published: 11 June 2015
Cited by 7 | PDF Full-text (3693 KB) | HTML Full-text | XML Full-text
Abstract
Lactic acid bacteria (LAB) have historically been used in food fermentations to preserve foods and are generally-recognized-as-safe (GRAS) by the FDA for use as food ingredients. In addition to lactic acid; some strains also produce bacteriocins that have been proposed for use as
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Lactic acid bacteria (LAB) have historically been used in food fermentations to preserve foods and are generally-recognized-as-safe (GRAS) by the FDA for use as food ingredients. In addition to lactic acid; some strains also produce bacteriocins that have been proposed for use as food preservatives. In this study we examined the inhibition of Listeria monocytogenes 39-2 by neutralized and non-neutralized bacteriocin preparations (Bac+ preps) produced by Lactobacillus curvatus FS47; Lb. curvatus Beef3; Pediococcus acidilactici Bac3; Lactococcus lactis FLS1; Enterococcus faecium FS56-1; and Enterococcus thailandicus FS92. Activity differences between non-neutralized and neutralized Bac+ preps in agar spot assays could not readily be attributed to acid because a bacteriocin-negative control strain was not inhibitory to Listeria in these assays. When neutralized and non-neutralized Bac+ preps were used in microplate growth inhibition assays against L. monocytogenes 39-2 we observed some differences attributed to acid inhibition. A microplate growth inhibition assay was used to compare inhibitory reactions of wild-type and bacteriocin-resistant variants of L. monocytogenes to differentiate bacteriocins with different modes-of-action (MOA) whereby curvaticins FS47 and Beef3, and pediocin Bac3 were categorized to be in MOA1; enterocins FS92 and FS56-1 in MOA2; and lacticin FLS1 in MOA3. The microplate bacteriocin MOA assay establishes a platform to evaluate the best combination of bacteriocin preparations for use in food applications as biopreservatives against L. monocytogenes. Full article
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Open AccessEditorial Introduction to Oxidative Stress in Biomedical and Biological Research
Biomolecules 2015, 5(2), 1169-1177; https://doi.org/10.3390/biom5021169
Received: 11 May 2015 / Revised: 1 June 2015 / Accepted: 4 June 2015 / Published: 9 June 2015
Cited by 5 | PDF Full-text (531 KB) | HTML Full-text | XML Full-text
Abstract
Oxidative stress is now a well-researched area with thousands of new articles appearing every year. We want to give the reader here an overview of the topics in biomedical and basic oxidative stress research which are covered by the authors of this thematic
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Oxidative stress is now a well-researched area with thousands of new articles appearing every year. We want to give the reader here an overview of the topics in biomedical and basic oxidative stress research which are covered by the authors of this thematic issue. We also want to give the newcomer a short introduction into some of the basic concepts, definitions and analytical procedures used in this field. Full article
(This article belongs to the Special Issue Oxidative Stress and Oxygen Radicals) Printed Edition available
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Open AccessReview CPSF30 at the Interface of Alternative Polyadenylation and Cellular Signaling in Plants
Biomolecules 2015, 5(2), 1151-1168; https://doi.org/10.3390/biom5021151
Received: 30 March 2015 / Revised: 26 May 2015 / Accepted: 29 May 2015 / Published: 8 June 2015
Cited by 13 | PDF Full-text (1539 KB) | HTML Full-text | XML Full-text
Abstract
Post-transcriptional processing, involving cleavage of precursor messenger RNA (pre mRNA), and further incorporation of poly(A) tail to the 3' end is a key step in the expression of genetic information. Alternative polyadenylation (APA) serves as an important check point for the regulation of
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Post-transcriptional processing, involving cleavage of precursor messenger RNA (pre mRNA), and further incorporation of poly(A) tail to the 3' end is a key step in the expression of genetic information. Alternative polyadenylation (APA) serves as an important check point for the regulation of gene expression. Recent studies have shown widespread prevalence of APA in diverse systems. A considerable amount of research has been done in characterizing different subunits of so-called Cleavage and Polyadenylation Specificity Factor (CPSF). In plants, CPSF30, an ortholog of the 30 kD subunit of mammalian CPSF is a key polyadenylation factor. CPSF30 in the model plant Arabidopsis thaliana was reported to possess unique biochemical properties. It was also demonstrated that poly(A) site choice in a vast majority of genes in Arabidopsis are CPSF30 dependent, suggesting a pivotal role of this gene in APA and subsequent regulation of gene expression. There are also indications of this gene being involved in oxidative stress and defense responses and in cellular signaling, suggesting a role of CPSF30 in connecting physiological processes and APA. This review will summarize the biochemical features of CPSF30, its role in regulating APA, and possible links with cellular signaling and stress response modules. Full article
(This article belongs to the Special Issue RNA-Binding Proteins—Structure, Function, Networks and Disease)
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Open AccessReview Hypoxia, Oxidative Stress and Fat
Biomolecules 2015, 5(2), 1143-1150; https://doi.org/10.3390/biom5021143
Received: 18 April 2015 / Revised: 19 May 2015 / Accepted: 19 May 2015 / Published: 8 June 2015
Cited by 23 | PDF Full-text (539 KB) | HTML Full-text | XML Full-text
Abstract
Metabolic disturbances in white adipose tissue in obese individuals contribute to the pathogenesis of insulin resistance and the development of type 2 diabetes mellitus. Impaired insulin action in adipocytes is associated with elevated lipolysis and increased free fatty acids leading to ectopic fat
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Metabolic disturbances in white adipose tissue in obese individuals contribute to the pathogenesis of insulin resistance and the development of type 2 diabetes mellitus. Impaired insulin action in adipocytes is associated with elevated lipolysis and increased free fatty acids leading to ectopic fat deposition in liver and skeletal muscle. Chronic adipose tissue hypoxia has been suggested to be part of pathomechanisms causing dysfunction of adipocytes. Hypoxia can provoke oxidative stress in human and animal adipocytes and reduce the production of beneficial adipokines, such as adiponectin. However, time-dose responses to hypoxia relativize the effects of hypoxic stress. Long-term exposure of fat cells to hypoxia can lead to the production of beneficial substances such as leptin. Knowledge of time-dose responses of hypoxia on white adipose tissue and the time course of generation of oxidative stress in adipocytes is still scarce. This paper reviews the potential links between adipose tissue hypoxia, oxidative stress, mitochondrial dysfunction, and low-grade inflammation caused by adipocyte hypertrophy, macrophage infiltration and production of inflammatory mediators. Full article
(This article belongs to the Special Issue Oxidative Stress and Oxygen Radicals) Printed Edition available
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Open AccessReview Interaction between Neuromelanin and Alpha-Synuclein in Parkinson’s Disease
Biomolecules 2015, 5(2), 1122-1142; https://doi.org/10.3390/biom5021122
Received: 15 March 2015 / Accepted: 29 April 2015 / Published: 5 June 2015
Cited by 10 | PDF Full-text (644 KB) | HTML Full-text | XML Full-text
Abstract
Parkinson’s disease (PD) is a very common neurodegenerative disorder characterized by the accumulation of α-synuclein (α-syn) into Lewy body (LB) inclusions and the loss of neuronmelanin (NM) containing dopamine (DA) neurons in the substantia nigra (SN). Pathological α-syn and NM are two prominent
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Parkinson’s disease (PD) is a very common neurodegenerative disorder characterized by the accumulation of α-synuclein (α-syn) into Lewy body (LB) inclusions and the loss of neuronmelanin (NM) containing dopamine (DA) neurons in the substantia nigra (SN). Pathological α-syn and NM are two prominent hallmarks in this selective and progressive neurodegenerative disease. Pathological α-syn can induce dopaminergic neuron death by various mechanisms, such as inducing oxidative stress and inhibiting protein degradation systems. Therefore, to explore the factors that trigger α-syn to convert from a non-toxic protein to toxic one is a pivotal question to clarify the mechanisms of PD pathogenesis. Many triggers for pathological α-syn aggregation have been identified, including missense mutations in the α-syn gene, higher concentration, and posttranslational modifications of α-Syn. Recently, the role of NM in inducing α-syn expression and aggregation has been suggested as a mechanism for this pigment to modulate neuronal vulnerability in PD. NM may be responsible for PD and age-associated increase and aggregation in α-syn. Here, we reviewed our previous study and other recent findings in the area of interaction between NM and α-syn. Full article
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Open AccessReview Advances and New Concepts in Alcohol-Induced Organelle Stress, Unfolded Protein Responses and Organ Damage
Biomolecules 2015, 5(2), 1099-1121; https://doi.org/10.3390/biom5021099
Received: 5 May 2015 / Revised: 23 May 2015 / Accepted: 26 May 2015 / Published: 3 June 2015
Cited by 13 | PDF Full-text (1017 KB) | HTML Full-text | XML Full-text
Abstract
Alcohol is a simple and consumable biomolecule yet its excessive consumption disturbs numerous biological pathways damaging nearly all organs of the human body. One of the essential biological processes affected by the harmful effects of alcohol is proteostasis, which regulates the balance between
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Alcohol is a simple and consumable biomolecule yet its excessive consumption disturbs numerous biological pathways damaging nearly all organs of the human body. One of the essential biological processes affected by the harmful effects of alcohol is proteostasis, which regulates the balance between biogenesis and turnover of proteins within and outside the cell. A significant amount of published evidence indicates that alcohol and its metabolites directly or indirectly interfere with protein homeostasis in the endoplasmic reticulum (ER) causing an accumulation of unfolded or misfolded proteins, which triggers the unfolded protein response (UPR) leading to either restoration of homeostasis or cell death, inflammation and other pathologies under severe and chronic alcohol conditions. The UPR senses the abnormal protein accumulation and activates transcription factors that regulate nuclear transcription of genes related to ER function. Similarly, this kind of protein stress response can occur in other cellular organelles, which is an evolving field of interest. Here, I review recent advances in the alcohol-induced ER stress response as well as discuss new concepts on alcohol-induced mitochondrial, Golgi and lysosomal stress responses and injuries. Full article
(This article belongs to the collection Multi-Organ Alcohol-Related Damage: Mechanisms and Treatment)
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Open AccessArticle Anti-Inflammatory Activity of Haskap Cultivars is Polyphenols-Dependent
Biomolecules 2015, 5(2), 1079-1098; https://doi.org/10.3390/biom5021079
Received: 19 January 2015 / Accepted: 22 May 2015 / Published: 2 June 2015
Cited by 14 | PDF Full-text (1761 KB) | HTML Full-text | XML Full-text
Abstract
Haskap (Lonicera caerulea L.) berries have long been used for their health promoting properties against chronic conditions. The current study investigated the effect of Canadian haskap berry extracts on pro-inflammatory cytokines using a human monocytic cell line THP-1 derived macrophages stimulated by
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Haskap (Lonicera caerulea L.) berries have long been used for their health promoting properties against chronic conditions. The current study investigated the effect of Canadian haskap berry extracts on pro-inflammatory cytokines using a human monocytic cell line THP-1 derived macrophages stimulated by lipopolysaccharide. Methanol extracts of haskap from different growing locations in Canada were prepared and characterized for their total phenolic profile using colorimetric assays and liquid chromatography—Mass spectrometry (UPLC-MS/MS). Human THP-1 monocytes were seeded in 24-well plates (5 × 105/well) and treated with phorbol 12-myristate 13-acetate (PMA, 0.1 μg/mL) for 48 h to induce macrophage differentiation. After 48 h, the differentiated macrophages were washed with Hank’s buffer and treated with various concentrations of test compounds for 4 h, followed by the lipopolysaccharide (LPS)-stimulation (18 h). Borealis cultivar showed the highest phenolic content, flavonoid content and anthocyanin content (p < 0.05). A negative correlation existed between the polyphenol concentration of the extracts and pro-inflammatory cytokines: Interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), prostaglandin (PGE2), and cyclooxygenase-2 (COX-2) enzyme. Borealis exhibited comparable anti-inflammatory effects to COX inhibitory drug, diclofenac. The results showed that haskap berry polyphenols has the potential to act as an effective inflammation inhibitor. Full article
(This article belongs to the Special Issue Oxidative Stress and Oxygen Radicals) Printed Edition available
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Open AccessReview Regulation of Transcription Elongation and Termination
Biomolecules 2015, 5(2), 1063-1078; https://doi.org/10.3390/biom5021063
Received: 9 April 2015 / Revised: 20 May 2015 / Accepted: 21 May 2015 / Published: 29 May 2015
Cited by 19 | PDF Full-text (1122 KB) | HTML Full-text | XML Full-text
Abstract
This article will review our current understanding of transcription elongation and termination in E. coli. We discuss why transcription elongation complexes pause at certain template sites and how auxiliary host and phage transcription factors affect elongation and termination. The connection between translation
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This article will review our current understanding of transcription elongation and termination in E. coli. We discuss why transcription elongation complexes pause at certain template sites and how auxiliary host and phage transcription factors affect elongation and termination. The connection between translation and transcription elongation is described. Finally we present an overview indicating where progress has been made and where it has not. Full article
(This article belongs to the Special Issue Bacterial RNA Polymerase)
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Open AccessReview Initial Events in Bacterial Transcription Initiation
Biomolecules 2015, 5(2), 1035-1062; https://doi.org/10.3390/biom5021035
Received: 28 March 2015 / Accepted: 14 May 2015 / Published: 27 May 2015
Cited by 34 | PDF Full-text (2238 KB) | HTML Full-text | XML Full-text
Abstract
Transcription initiation is a highly regulated step of gene expression. Here, we discuss the series of large conformational changes set in motion by initial specific binding of bacterial RNA polymerase (RNAP) to promoter DNA and their relevance for regulation. Bending and wrapping of
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Transcription initiation is a highly regulated step of gene expression. Here, we discuss the series of large conformational changes set in motion by initial specific binding of bacterial RNA polymerase (RNAP) to promoter DNA and their relevance for regulation. Bending and wrapping of the upstream duplex facilitates bending of the downstream duplex into the active site cleft, nucleating opening of 13 bp in the cleft. The rate-determining opening step, driven by binding free energy, forms an unstable open complex, probably with the template strand in the active site. At some promoters, this initial open complex is greatly stabilized by rearrangements of the discriminator region between the −10 element and +1 base of the nontemplate strand and of mobile in-cleft and downstream elements of RNAP. The rate of open complex formation is regulated by effects on the rapidly-reversible steps preceding DNA opening, while open complex lifetime is regulated by effects on the stabilization of the initial open complex. Intrinsic DNA opening-closing appears less regulated. This noncovalent mechanism and its regulation exhibit many analogies to mechanisms of enzyme catalysis. Full article
(This article belongs to the Special Issue Bacterial RNA Polymerase)
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Open AccessReview Transcriptional Regulation of Chemokine Genes: A Link to Pancreatic Islet Inflammation?
Biomolecules 2015, 5(2), 1020-1034; https://doi.org/10.3390/biom5021020
Received: 20 April 2015 / Accepted: 12 May 2015 / Published: 26 May 2015
Cited by 7 | PDF Full-text (165 KB) | HTML Full-text | XML Full-text
Abstract
Enhanced expression of chemotactic cytokines (aka chemokines) within pancreatic islets likely contributes to islet inflammation by regulating the recruitment and activation of various leukocyte populations, including macrophages, neutrophils, and T-lymphocytes. Because of the powerful actions of these chemokines, precise transcriptional control is required.
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Enhanced expression of chemotactic cytokines (aka chemokines) within pancreatic islets likely contributes to islet inflammation by regulating the recruitment and activation of various leukocyte populations, including macrophages, neutrophils, and T-lymphocytes. Because of the powerful actions of these chemokines, precise transcriptional control is required. In this review, we highlight what is known about the signals and mechanisms that govern the transcription of genes encoding specific chemokine proteins in pancreatic islet β-cells, which include contributions from the NF-κB and STAT1 pathways. We further discuss increased chemokine expression in pancreatic islets during autoimmune-mediated and obesity-related development of diabetes. Full article
(This article belongs to the Special Issue Transcriptional Regulation of Pro-Inflammatory Genes)
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Open AccessReview A Perspective on the Enhancer Dependent Bacterial RNA Polymerase
Biomolecules 2015, 5(2), 1012-1019; https://doi.org/10.3390/biom5021012
Received: 2 April 2015 / Accepted: 15 May 2015 / Published: 21 May 2015
Cited by 5 | PDF Full-text (941 KB) | HTML Full-text | XML Full-text
Abstract
Here we review recent findings and offer a perspective on how the major variant RNA polymerase of bacteria, which contains the sigma54 factor, functions for regulated gene expression. We consider what gaps exist in our understanding of its genetic, biochemical and biophysical functioning
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Here we review recent findings and offer a perspective on how the major variant RNA polymerase of bacteria, which contains the sigma54 factor, functions for regulated gene expression. We consider what gaps exist in our understanding of its genetic, biochemical and biophysical functioning and how they might be addressed. Full article
(This article belongs to the Special Issue Bacterial RNA Polymerase)
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Open AccessReview Role of α- and β-Synucleins in the Axonal Pathology of Parkinson’s Disease and Related Synucleinopathies
Biomolecules 2015, 5(2), 1000-1011; https://doi.org/10.3390/biom5021000
Received: 7 April 2015 / Revised: 1 May 2015 / Accepted: 12 May 2015 / Published: 19 May 2015
Cited by 7 | PDF Full-text (1032 KB) | HTML Full-text | XML Full-text
Abstract
Axonal swellings are histological hallmarks of axonopathies in various types of disorders in the central nervous system, including neurodegenerative diseases. Given the pivotal role of axonopathies during the early phase of neurodegenerative process, axonal swellings may be good models which may provide some
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Axonal swellings are histological hallmarks of axonopathies in various types of disorders in the central nervous system, including neurodegenerative diseases. Given the pivotal role of axonopathies during the early phase of neurodegenerative process, axonal swellings may be good models which may provide some clues for early pathogenesis of α-synucleinopathies, including Parkinson’s disease and dementia with Lewy bodies (DLB). In this mini-review, such a possibility is discussed based on our recent studies as well as other accumulating studies. Consistent with the current view that dysfunction in the autophagy-lysosomal system may play a major role in the formation of axonal swellings, our studies showed globule, small axonal swellings, derived from transgenic mice expressing either human wild-type α-synuclein (αS-globule) or DLB-linked P123H β-synuclein (βS-globule), contained autophagosome-like membranes. However, other pathological features, such as abnormal mitochondria, enhanced oxidative stress and LRRK2 accumulation, were observed in the αS-globules, but not in the βS-globules. Collectively, it is predicted that αS and βS may be involved in axonopathies through similar but distinct mechanisms, and thus, contribute to diverse axonal pathologies. Further studies of the axonal swellings may lead to elucidating the pathogenic mechanism of early α-synucleinopathies and illuminating a strategy for a disease-modifying therapy against these devastating disorders. Full article
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Open AccessReview Roles of Prolyl Isomerases in RNA-Mediated Gene Expression
Biomolecules 2015, 5(2), 974-999; https://doi.org/10.3390/biom5020974
Received: 31 March 2015 / Revised: 1 May 2015 / Accepted: 7 May 2015 / Published: 18 May 2015
Cited by 6 | PDF Full-text (2594 KB) | HTML Full-text | XML Full-text
Abstract
The peptidyl-prolyl cis-trans isomerases (PPIases) that include immunophilins (cyclophilins and FKBPs) and parvulins (Pin1, Par14, Par17) participate in cell signaling, transcription, pre-mRNA processing and mRNA decay. The human genome encodes 19 cyclophilins, 18 FKBPs and three parvulins. Immunophilins are receptors for the immunosuppressive
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The peptidyl-prolyl cis-trans isomerases (PPIases) that include immunophilins (cyclophilins and FKBPs) and parvulins (Pin1, Par14, Par17) participate in cell signaling, transcription, pre-mRNA processing and mRNA decay. The human genome encodes 19 cyclophilins, 18 FKBPs and three parvulins. Immunophilins are receptors for the immunosuppressive drugs cyclosporin A, FK506, and rapamycin that are used in organ transplantation. Pin1 has also been targeted in the treatment of Alzheimer’s disease, asthma, and a number of cancers. While these PPIases are characterized as molecular chaperones, they also act in a nonchaperone manner to promote protein-protein interactions using surfaces outside their active sites. The immunosuppressive drugs act by a gain-of-function mechanism by promoting protein-protein interactions in vivo. Several immunophilins have been identified as components of the spliceosome and are essential for alternative splicing. Pin1 plays roles in transcription and RNA processing by catalyzing conformational changes in the RNA Pol II C-terminal domain. Pin1 also binds several RNA binding proteins such as AUF1, KSRP, HuR, and SLBP that regulate mRNA decay by remodeling mRNP complexes. The functions of ribonucleoprotein associated PPIases are largely unknown. This review highlights PPIases that play roles in RNA-mediated gene expression, providing insight into their structures, functions and mechanisms of action in mRNP remodeling in vivo. Full article
(This article belongs to the Special Issue RNA-Binding Proteins—Structure, Function, Networks and Disease)
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Open AccessArticle Sulfatide-Hsp70 Interaction Promotes Hsp70 Clustering and Stabilizes Binding to Unfolded Protein
Biomolecules 2015, 5(2), 958-973; https://doi.org/10.3390/biom5020958
Received: 26 February 2015 / Revised: 24 April 2015 / Accepted: 7 May 2015 / Published: 15 May 2015
Cited by 4 | PDF Full-text (2035 KB) | HTML Full-text | XML Full-text
Abstract
The 70-kDa heat shock protein (Hsp70), one of the major stress-inducible molecular chaperones, is localized not only in the cytosol, but also in extracellular milieu in mammals. Hsp70 interacts with various cell surface glycolipids including sulfatide (3'-sulfogalactosphingolipid). However, the molecular mechanism, as well
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The 70-kDa heat shock protein (Hsp70), one of the major stress-inducible molecular chaperones, is localized not only in the cytosol, but also in extracellular milieu in mammals. Hsp70 interacts with various cell surface glycolipids including sulfatide (3'-sulfogalactosphingolipid). However, the molecular mechanism, as well as the biological relevance, underlying the glycolipid-Hsp70 interaction is unknown. Here we report that sulfatide promotes Hsp70 oligomerization through the N-terminal ATPase domain, which stabilizes the binding of Hsp70 to unfolded protein in vitro. We find that the Hsp70 oligomer has apparent molecular masses ranging from 440 kDa to greater than 669 kDa. The C-terminal peptide-binding domain is dispensable for the sulfatide-induced oligomer formation. The oligomer formation is impaired in the presence of ATP, while the Hsp70 oligomer, once formed, is unable to bind to ATP. These results suggest that sulfatide locks Hsp70 in a high-affinity state to unfolded proteins by clustering the peptide-binding domain and blocking the binding to ATP that induces the dissociation of Hsp70 from protein substrates. Full article
(This article belongs to the Special Issue Challenges in Glycan, Glycoprotein and Proteoglycan Research)
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Open AccessReview RNA-Mediated Regulation of HMGA1 Function
Biomolecules 2015, 5(2), 943-957; https://doi.org/10.3390/biom5020943
Received: 31 March 2015 / Accepted: 5 May 2015 / Published: 14 May 2015
Cited by 12 | PDF Full-text (697 KB) | HTML Full-text | XML Full-text
Abstract
The high mobility group protein A1 (HMGA1) is a master regulator of chromatin structure mediating its major gene regulatory activity by direct interactions with A/T-rich DNA sequences located in the promoter and enhancer regions of a large variety of genes. HMGA1 DNA-binding through
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The high mobility group protein A1 (HMGA1) is a master regulator of chromatin structure mediating its major gene regulatory activity by direct interactions with A/T-rich DNA sequences located in the promoter and enhancer regions of a large variety of genes. HMGA1 DNA-binding through three AT-hook motifs results in an open chromatin structure and subsequently leads to changes in gene expression. Apart from its significant expression during development, HMGA1 is over-expressed in virtually every cancer, where HMGA1 expression levels correlate with tumor malignancy. The exogenous overexpression of HMGA1 can lead to malignant cell transformation, assigning the protein a key role during cancerogenesis. Recent studies have unveiled highly specific competitive interactions of HMGA1 with cellular and viral RNAs also through an AT-hook domain of the protein, significantly impacting the HMGA1-dependent gene expression. In this review, we discuss the structure and function of HMGA1-RNA complexes during transcription and epigenomic regulation and their implications in HMGA1-related diseases. Full article
(This article belongs to the Special Issue RNA-Binding Proteins—Structure, Function, Networks and Disease)
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