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https://www.readbyqxmd.com/read/28102469/lanosterol-suppresses-the-aggregation-and-cytotoxicity-of-misfolded-proteins-linked-with-neurodegenerative-diseases
#1
Arun Upadhyay, Ayeman Amanullah, Ribhav Mishra, Amit Kumar, Amit Mishra
Accumulation of misfolded or aberrant proteins in neuronal cells is linked with neurodegeneration and other pathologies. Which molecular mechanisms fail and cause inappropriate folding of proteins and what is their relationship to cellular toxicity is not well known. How does it happen and what are the probable therapeutic or molecular approaches to counter them are also not clear. Here, we demonstrate that treatment of lanosterol diminishes aberrant proteotoxic aggregation and mitigates their cytotoxicity via induced expression of co-chaperone CHIP and elevated autophagy...
January 19, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28101870/fibrillar-collagens
#2
Jordi Bella, David J S Hulmes
Fibrillar collagens (types I, II, III, V, XI, XXIV and XXVII) constitute a sub-group within the collagen family (of which there are 28 types in humans) whose functions are to provide three-dimensional frameworks for tissues and organs. These networks confer mechanical strength as well as signalling and organizing functions through binding to cellular receptors and other components of the extracellular matrix (ECM). Here we describe the structure and assembly of fibrillar collagens, and their procollagen precursors, from the molecular to the tissue level...
2017: Sub-cellular Biochemistry
https://www.readbyqxmd.com/read/28101866/titin-and-nebulin-in-thick-and-thin-filament-length-regulation
#3
Larissa Tskhovrebova, John Trinick
In this review we discuss the history and the current state of ideas related to the mechanism of size regulation of the thick (myosin) and thin (actin) filaments in vertebrate striated muscles. Various hypotheses have been considered during of more than half century of research, recently mostly involving titin and nebulin acting as templates or 'molecular rulers', terminating exact assembly. These two giant, single-polypeptide, filamentous proteins are bound in situ along the thick and thin filaments, respectively, with an almost perfect match in the respective lengths and structural periodicities...
2017: Sub-cellular Biochemistry
https://www.readbyqxmd.com/read/28101863/lessons-from-animal-models-of-cytoplasmic-intermediate-filament-proteins
#4
Jamal-Eddine Bouameur, Thomas M Magin
Cytoplasmic intermediate filaments (IFs) represent a major cytoskeletal network contributing to cell shape, adhesion and migration as well as to tissue resilience and renewal in numerous bilaterians, including mammals. The observation that IFs are dispensable in cultured mammalian cells, but cause tissue-specific, life-threatening disorders, has pushed the need to investigate their function in vivo. In keeping with human disease, the deletion or mutation of murine IF genes resulted in highly specific pathologies...
2017: Sub-cellular Biochemistry
https://www.readbyqxmd.com/read/28100667/the-control-of-translational-accuracy-is-a-determinant-of-healthy-ageing-in-yeast
#5
Tobias von der Haar, Jane E Leadsham, Aimie Sauvadet, Daniel Tarrant, Ilectra S Adam, Kofo Saromi, Peter Laun, Mark Rinnerthaler, Hannelore Breitenbach-Koller, Michael Breitenbach, Mick F Tuite, Campbell W Gourlay
Life requires the maintenance of molecular function in the face of stochastic processes that tend to adversely affect macromolecular integrity. This is particularly relevant during ageing, as many cellular functions decline with age, including growth, mitochondrial function and energy metabolism. Protein synthesis must deliver functional proteins at all times, implying that the effects of protein synthesis errors like amino acid misincorporation and stop-codon read-through must be minimized during ageing. Here we show that loss of translational accuracy accelerates the loss of viability in stationary phase yeast...
January 2017: Open Biology
https://www.readbyqxmd.com/read/28097424/analysis-of-the-spleen-proteome-of-chickens-infected-with-reticuloendotheliosis-virus
#6
Mei Xue, Yan Zhao, Shunlei Hu, Xingming Shi, Hongyu Cui, Yunfeng Wang
Infection with reticuloendotheliosis virus (REV), a gammaretrovirus in the family Retroviridae, can result in immunosuppression and subsequent increased susceptibility to secondary infections. In the present study, we identified differentially expressed proteins in the spleens of chickens infected with the REV-A HLJ07I strain, using two-dimensional gel electrophoresis on samples from time points coinciding with different phases of the REV life cycle. Differentially expressed proteins were identified using one-dimensional liquid chromatography electrospray ionization tandem mass spectrometry (1D LC ESI MS/MS)...
January 17, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28096332/human-nf-%C3%AE%C2%BAb-repressing-factor-acts-as-a-stress-regulated-switch-for-ribosomal-rna-processing-and-nucleolar-homeostasis-surveillance
#7
Marta Coccia, Antonio Rossi, Anna Riccio, Edoardo Trotta, Maria Gabriella Santoro
The nucleolus, a dynamic nuclear compartment long regarded as the cell ribosome factory, is emerging as an important player in the regulation of cell survival and recovery from stress. In larger eukaryotes, the stress-induced transcriptional response is mediated by a family of heat-shock transcription factors. Among these, HSF1, considered the master regulator of stress-induced transcriptional responses, controls the expression of cytoprotective heat shock proteins (HSPs), molecular chaperones/cochaperones constituting a major component of the cell protein quality control machinery essential to circumvent stress-induced degradation and aggregation of misfolded proteins...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28095607/heat-shock-protein-70-promotes-coxsackievirus-b3-translation-initiation-and-elongation-via-akt-mtorc1-pathway-depending-on-activation-of-p70s6k-and-cdc2
#8
Fengping Wang, Ye Qiu, Huifang M Zhang, Paul Hanson, Xin Ye, Guangze Zhao Ronald Xie, Lei Tong, Decheng Yang
We previously demonstrated that coxsackievirus B3 (CVB3) infection upregulated heat shock protein 70 (Hsp70) and promoted CVB3 multiplication. Here, we report the underlying mechanism by which Hsp70 enhances viral RNA translation. By using an Hsp70-overexpressing cell line infected with CVB3, we found that Hsp70 enhanced CVB3 VP1 translation at two stages. First, Hsp70 induced upregulation of VP1 translation at the initiation stage via upregulation of IRES trans-acting factor La protein and activation of eIF4E binding protein 1, a cap-dependent translation suppressor...
January 17, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28095400/computational-analysis-of-residue-interaction-networks-and-coevolutionary-relationships-in-the-hsp70-chaperones-a-community-hopping-model-of-allosteric-regulation-and-communication
#9
Gabrielle Stetz, Gennady M Verkhivker
Allosteric interactions in the Hsp70 proteins are linked with their regulatory mechanisms and cellular functions. Despite significant progress in structural and functional characterization of the Hsp70 proteins fundamental questions concerning modularity of the allosteric interaction networks and hierarchy of signaling pathways in the Hsp70 chaperones remained largely unexplored and poorly understood. In this work, we proposed an integrated computational strategy that combined atomistic and coarse-grained simulations with coevolutionary analysis and network modeling of the residue interactions...
January 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28092737/complex-molecular-changes-induced-by-chronic-progestogens-exposure-in-roach-rutilus-rutilus
#10
Gabor Maasz, Zita Zrinyi, Peter Takacs, Sandor Lovas, Istvan Fodor, Tibor Kiss, Zsolt Pirger
In our previous study, we measured 0.23-13.67ng/L progestogens (progesterone, drospirenone, levonorgestrel) in natural waters in the catchment area of the largest shallow lake of Central Europe, Lake Balaton. Progestogen contaminations act as potent steroids with mixed progestagenic, androgenic and mild estrogenic effects that is why our aim was to investigate the morphological and molecular effects of mixture of progesterone, drospirenone, and levonorgestrel in environmentally relevant (10ng/L) and higher (50 and 500ng/L) exposure concentrations in common roach, Rutilus rutilus...
January 13, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28090761/modest-overexpression-of-foxo-maintains-cardiac-proteostasis-and-ameliorates-age-associated-functional-decline
#11
Anna C Blice-Baum, Alexander C Zambon, Gaurav Kaushik, Meera C Viswanathan, Adam J Engler, Rolf Bodmer, Anthony Cammarato
Heart performance declines with age. Impaired protein quality control (PQC), due to reduced ubiquitin-proteasome system (UPS) activity, autophagic function, and/or chaperone-mediated protein refolding, contributes to cardiac deterioration. The transcription factor FOXO participates in regulating genes involved in PQC, senescence, and numerous other processes. Here, a comprehensive approach, involving molecular genetics, novel assays to probe insect cardiac physiology, and bioinformatics, was utilized to investigate the influence of heart-restricted manipulation of dFOXO expression in the rapidly aging Drosophila melanogaster model...
February 2017: Aging Cell
https://www.readbyqxmd.com/read/28079009/emerging-roles-of-calreticulin-in-cancer-implications-for-therapy
#12
Kavya Venkateswaran, Amit Verma, Anant Narayan Bhatt, Anju Shrivastava, Kailash Manda, Hanumantharao G Raj, Ashok Prasad, Christophe Len, Virinder S Parmar, Bilikere Dwarakanath
Calreticulin (CRT), initially identified as a ubiquitous calcium-binding protein in the endoplasmic reticulum, has emerged as a multifunctional protein with roles in calcium homeostasis, molecular chaperoning and cell adhesion. Emerging evidence suggests its involvement in tumorigenesis facilitating proliferation, migration, and adhesion. CRT translocated to the cell surface (ecto-CRT) serves as a phagocytic signal for immunogenic cell death (ICD) mediated through dendritic cells (DCs) and cytotoxic T-cell activation thereby making tumors susceptible to immunotherapy-based anti-cancer strategies...
January 11, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/28078663/inhibition-of-hsp90-exerts-anti-tumor-effect-on-angiosarcoma-involvement-of-vegf-signaling-pathway
#13
S Yamada-Kanazawa, I Kajihara, S Fukushima, M Jinnin, M Masuzawa, M Masuzawa, Y Amoh, D Hoshina, R Abe, H Ihn
BACKGROUND: Angiosarcoma is a rare malignant neoplasm derived from endothelial cells and its prognosis is poor because advanced angiosarcoma is resistant to standard chemotherapy, and new therapies are urgently needed. Heat shock protein 90 (HSP90) has been identified as a molecular chaperone that regulates various cancer-related proteins. Numerous clinical trials are testing the effectiveness of HSP90 inhibitors in various types of malignancies. OBJECTIVES: To investigate the role of HSP90 in the pathogenesis of angiosarcoma and whether inhibition of HSP90 may have anti-tumor activity...
January 12, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28077174/mutant-hspb1-causes-loss-of-translational-repression-by-binding-to-pcbp1-an-rna-binding-protein-with-a-possible-role-in-neurodegenerative-disease
#14
Thomas Geuens, Vicky De Winter, Nicholas Rajan, Tilmann Achsel, Ligia Mateiu, Leonardo Almeida-Souza, Bob Asselbergh, Delphine Bouhy, Michaela Auer-Grumbach, Claudia Bagni, Vincent Timmerman
The small heat shock protein HSPB1 (Hsp27) is an ubiquitously expressed molecular chaperone able to regulate various cellular functions like actin dynamics, oxidative stress regulation and anti-apoptosis. So far disease causing mutations in HSPB1 have been associated with neurodegenerative diseases such as distal hereditary motor neuropathy, Charcot-Marie-Tooth disease and amyotrophic lateral sclerosis. Most mutations in HSPB1 target its highly conserved α-crystallin domain, while other mutations affect the C- or N-terminal regions or its promotor...
January 11, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28076420/chaperone-mediated-autophagy-protein-bag3-negatively-regulates-ebola-and-marburg-vp40-mediated-egress
#15
Jingjing Liang, Cari A Sagum, Mark T Bedford, Sachdev S Sidhu, Marius Sudol, Ziying Han, Ronald N Harty
Ebola (EBOV) and Marburg (MARV) viruses are members of the Filoviridae family which cause outbreaks of hemorrhagic fever. The filovirus VP40 matrix protein is essential for virus assembly and budding, and its PPxY L-domain motif interacts with WW-domains of specific host proteins, such as Nedd4 and ITCH, to facilitate the late stage of virus-cell separation. To identify additional WW-domain-bearing host proteins that interact with VP40, we used an EBOV PPxY-containing peptide to screen an array of 115 mammalian WW-domain-bearing proteins...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28074868/nucleoplasmin-like-domain-of-fkbp39-from-drosophila-melanogaster-forms-a-tetramer-with-partly-disordered-tentacle-like-c-terminal-segments
#16
Małgorzata Kozłowska, Aneta Tarczewska, Michał Jakób, Dominika Bystranowska, Michał Taube, Maciej Kozak, Mariusz Czarnocki-Cieciura, Andrzej Dziembowski, Marek Orłowski, Katarzyna Tkocz, Andrzej Ożyhar
Nucleoplasmins are a nuclear chaperone family defined by the presence of a highly conserved N-terminal core domain. X-ray crystallographic studies of isolated nucleoplasmin core domains revealed a β-propeller structure consisting of a set of five monomers that together form a stable pentamer. Recent studies on isolated N-terminal domains from Drosophila 39-kDa FK506-binding protein (FKBP39) and from other chromatin-associated proteins showed analogous, nucleoplasmin-like (NPL) pentameric structures. Here, we report that the NPL domain of the full-length FKBP39 does not form pentameric complexes...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28074336/small-heat-shock-proteins-in-ageing-and-age-related-diseases
#17
REVIEW
Nikolaos Charmpilas, Emmanouil Kyriakakis, Nektarios Tavernarakis
Small heat shock proteins (sHSPs) are gatekeepers of cellular homeostasis across species, preserving proteome integrity under stressful conditions. Nonetheless, recent evidence suggests that sHSPs are more than molecular chaperones with merely auxiliary role. In contrast, sHSPs have emerged as central lifespan determinants, and their malfunction has been associated with the manifestation of neurological disorders, cardiovascular disease and cancer malignancies. In this review, we focus on the role of sHSPs in ageing and age-associated diseases and highlight the most prominent paradigms, where impairment of sHSP function has been implicated in human pathology...
January 10, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28073182/over-expression-of-the-molecular-chaperone-hsp104-in-saccharomyces-cerevisiae-results-in-the-malpartition-of-psi-propagons
#18
Frederique Ness, Brian S Cox, Jintana Wongwigkarn, Wesley R Naeimi, Mick F Tuite
The ability of a yeast cell to propagate [PSI(+) ], the prion form of the Sup35 protein, is dependent on the molecular chaperone Hsp104. Inhibition of Hsp104 function in yeast cells leads to a failure to generate new propagons, the molecular entities necessary for [PSI(+) ] propagation in dividing cells and they get diluted out as cells multiply. Over-expression of Hsp104 also leads to [PSI(+) ] prion loss and this has been assumed to arise from the complete disaggregation of the Sup35 prion polymers. However, in conditions of Hsp104 over-expression in [PSI(+) ] cells we find no release of monomers from Sup35 polymers, no monomerisation of aggregated Sup35 which is not accounted for by the proportion of prion-free [psi(-) ] cells present, no change in the molecular weight of Sup35-containing SDS-resistant polymers and no significant decrease in average propagon numbers in the population as a whole...
January 10, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28072820/p-cymene-promotes-its-catabolism-through-the-p-cymene-and-the-p-cumate-pathways-activates-a-stress-response-and-reduces-the-biofilm-formation-in-burkholderia-xenovorans-lb400
#19
Loreine Agulló, María José Romero-Silva, Mirian Domenech, Michael Seeger
p-Cymene is an aromatic terpene that is present in diverse plant species. The aims of this study were to study the p-cymene metabolism in the model aromatic-degrading bacterium Burkholderia xenovorans LB400, and its response to p-cymene. The catabolic p-cymene (cym) and p-cumate (cmt) genes are clustered on the LB400 major chromosome. B. xenovorans LB400 was able to grow on p-cymene as well as on p-cumate as a sole carbon and energy sources. LB400 growth attained higher cell concentration at stationary phase on p-cumate than on p-cymene...
2017: PloS One
https://www.readbyqxmd.com/read/28069662/endoplasmic-reticulum-stress-inhibition-limits-the-progression-of-chronic-kidney-disease-in-the-dahl-salt-sensitive-rat
#20
Victoria Yum, Rachel E Carlisle, Chao Lu, Elise Brimble, Jasmine Chahal, Chandak Upagupta, Kjetil Ask, Jeffrey G Dickhout
Proteinuria is one of the primary risk factors for the progression of chronic kidney disease (CKD) and has been implicated in the induction of endoplasmic reticulum (ER) stress. We hypothesized that the suppression of ER stress with a low molecular weight chemical chaperone, 4-phenylbutyric acid (4-PBA), would reduce the severity of CKD and proteinuria in the Dahl salt-sensitive (SS) hypertensive rat. To induce hypertension and CKD, 12-wk-old male rats were placed on a high-salt (HS) diet for 4 wk with or without 4-PBA treatment...
January 1, 2017: American Journal of Physiology. Renal Physiology
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