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FEBS Journal

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https://www.readbyqxmd.com/read/29971953/interferon-regulatory-factor-5-and-nuclear-factor-kappa-b-exhibit-cooperating-but-also-divergent-roles-in-the-regulation-of-pro-inflammatory-cytokines-important-for-the-development-of-th1-and-th17-responses
#1
Thomas Stein, Audrey Wollschlegel, Helene Te, Jessica Weiss, Kushal Joshi, Bernd Kinzel, Andreas Billich, Christine Guntermann, Joachim C U Lehmann
A large body of data demonstrates that interferon regulatory factor 5 (IRF5) and nuclear factor kappa B (NF-κB) are the two major transcription factors in classically activated macrophages responsible for the transcriptional control of pro-inflammatory genes. Although recent evidence suggests that IRF5 interacts with certain members of the nuclear factor kappa B pathway, the extent of cooperation and its implications in disease are ambiguous. Since both pathways are known for their strong contributions in TLR8 signaling we used the human monocytic cell line THP-1...
July 3, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29956459/genetic-interaction-between-dna-replication-and-the-notch-signaling-pathway
#2
Morris F Maduro
The Notch pathway is a widely conserved cell signaling system found in most metazoans. In Caenorhabditis elegans, GLP-1/Notch signaling is required for developmental cell fate decisions in multiple contexts. A recent report provides a potential link between DNA replication and Notch-dependent proliferation in the C. elegans germline.
June 29, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29953728/chip-promotes-autophagy-mediated-degradation-of-aggregating-mutant-p53-in-hypoxic-conditions
#3
Meenu Maan, Uttam Pati
Tumor suppressor protein p53 aggregates in hypoxic core of solid tumor. The C-terminus of Hsc70-interacting protein CHIP displays chaperone as well as E3 ligase activities in both stabilizing and degrading wild type and mutant p53. In this study we have discovered that CHIP selectively degrades p53 aggregating mutants under both normal and hypoxic condition. Silencing of CHIP alleviates degradation of aggregating p53 mutants both in normoxia and hypoxia whereas CHIP silencing has no significant effect on the level of non aggregating mutants...
June 28, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29953723/stimulation-of-exosome-release-by-extracellular-dna-is-conserved-across-multiple-cell-types
#4
Dimitar Iliev, Guro Strandskog, Arpita Nepal, Augusta Aspar, Randi Olsen, Jorunn Jørgensen, Deanna Wolfson, Balpreet Singh Ahluwalia, Jordan Handzhiyski, Roumyana Mironova
Exosomes are distinguished from other types of extracellular vesicles by their small and relatively uniform size (30-100 nm) and their composition which reflects their endo-lysosomal origin. Involvement of these extracellular organelles in intercellular communication and their implication in pathological conditions has fuelled intensive research on mammalian exosomes; however, currently, very little is known about exosomes in lower vertebrates. Here we show that, in primary cultures of head kidney leukocytes from Atlantic salmon (Salmo salar), phosphorothioate CpG oligodeoxynucleotides induce secretion of vesicles with characteristics very similar to these of mammalian exosomes...
June 28, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29949239/a-route-to-understanding-yeast-cellular-envelope-plasma-membrane-lipids-interplaying-in-cell-wall-integrity
#5
Rodrigo F M de Almeida
Sphingolipids and sterols are major components of the plasma membrane in eukaryotic cells. A recent study provides new insight into the intricate but fundamental relationship between Saccharomyces cerevisiae membrane lipid composition and membrane biophysical properties, by showing that sphingolipids and sterols co-ordinately regulate cell wall integrity.
June 27, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29974999/the-mocr-like-transcription-factors-pyridoxal-5-phosphate-dependent-regulators-of-bacterial-metabolism
#6
Angela Tramonti, Caterina Nardella, Martino L di Salvo, Stefano Pascarella, Roberto Contestabile
Many biological functions played by current proteins were not created by evolution from scratch, rather they were obtained combining already available protein scaffolds. This is the case of MocR-like bacterial transcription factors (MocR-TFs), a subclass of GntR transcription regulators, whose structure is the outcome of the fusion between DNA-binding proteins and pyridoxal 5'-phosphate (PLP)-dependent enzymes. The resultant chimeras can count on the properties of both protein classes, i.e. the capability to recognize specific DNA sequences and to bind PLP and amino-compounds; it is the modulation of such binding properties to confer to MocR-TFs chimeras the ability to interact with effector molecules and DNA so as to regulate transcription...
June 26, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29943906/deciphering-the-mechanism-of-potent-peptidomimetic-inhibitors-targeting-plasmepsins-biochemical-and-structural-insights
#7
Vandana Mishra, Ishan Rathore, Anagha Arekar, Lakshmi Kavitha Sthanam, Huogen Xiao, Yoshiaki Kiso, Shamik Sen, Swati Patankar, Alla Gustchina, Koushi Hidaka, Alexander Wlodawer, Rickey Y Yada, Prasenjit Bhaumik
Malaria is a deadly disease killing worldwide hundreds of thousands people each year and the responsible parasite has acquired resistance to the available drug combinations. The four vacuolar plasmepsins (PMs) in Plasmodium falciparum involved in hemoglobin catabolism represent promising targets to combat drug resistance. High antimalarial activities can be achieved by developing a single drug that would simultaneously target all the vacuolar PMs. We have demonstrated for the first time the use of soluble recombinant plasmepsin II (PMII) for structure-guided drug discovery with KNI inhibitors...
June 26, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29938896/expansion-microscopy-enabling-single-cell-analysis-in-intact-biological-systems
#8
REVIEW
Shahar Alon, Grace H Huynh, Edward S Boyden
There is a need for single cell analysis methods that enable the identification and localization of different kinds of biomolecule throughout cells and throughout intact tissues, thereby allowing characterization and classification of individual cells and their relationships to each other within intact systems. Expansion microscopy (ExM) is a technology that physically magnifies tissues in an isotropic way, thereby achieving super-resolution microscopy on diffraction-limited microscopes, enabling rapid image acquisition and large field of view...
June 25, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29935061/targeting-transglutaminase-2-partially-restores-extracellular-matrix-structure-but-not-alveolar-architecture-in-experimental-bronchopulmonary-dysplasia
#9
Ivana Mižíková, Tilman Pfeffer, Claudio Nardiello, David E Surate Solaligue, Heiko Steenbock, Hideki Tatsukawa, Diogo M Silva, István Vadász, Susanne Herold, Richard J Pease, Siiri E Iismaa, Kiyotaka Hitomi, Werner Seeger, Jürgen Brinckmann, Rory E Morty
The generation, maturation and remodelling of the extracellular matrix (ECM) are essential for the formation of alveoli during lung development. Alveoli formation is disturbed in preterm infants that develop bronchopulmonary dysplasia (BPD), where collagen fibres are malformed, and perturbations to lung ECM structures may underlie BPD pathogenesis. Malformed ECM structures might result from abnormal protein cross-linking, in part attributable to the increased expression and activity of transglutaminase 2 (TGM2) that have been noted in affected patient lungs, as well as in hyperoxia-based BPD animal models...
June 23, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29935055/ubiquitin-ligase-traf2-attenuates-the-transcriptional-activity-of-the-core-clock-protein-bmal1-and-affects-the-maximal-per1-mrna-level-of-the-circadian-clock-in-cells
#10
Suping Chen, Jing Yang, Lu Yang, Yang Zhang, Liang Zhou, Qing Liu, Chunyan Duan, Crystal A Mieres, Guanghai Zhou, Guoqiang Xu
The ubiquitin-proteasome system (UPS) modulates the ubiquitination and degradation of many proteins and thus alters their abundance and biological functions. The core clock protein, aryl hydrocarbon receptor nuclear translocator-like protein 1 (BMAL1), is the master regulator of the circadian clock and plays important roles in the regulation of many biological processes, such as protein synthesis, cell senescence, and circadian rhythms. However, the influence of the UPS on BMAL1 is not fully understood. Here, we find an E3 ubiquitin ligase, TNF receptor-associated factor 2 (TRAF2), as an interacting protein of BMAL1 to reduce its stability...
June 23, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29933522/deuterium-reinforced-linoleic-acid-lowers-lipid-peroxidation-and-mitigates-cognitive-impairment-in-the-q140-knock-in-mouse-model-of-huntington-s-disease
#11
Asa Hatami, Chunni Zhu, Aroa Relaño-Gines, Chris Elias, Arpine Galstyan, Michael Jun, Ginger Milne, Charles R Cantor, Marie-Francoise Chesselet, Mikhail S Shchepinov
Huntington's disease (HD) is an autosomal dominant neurodegenerative disease which has no effective treatment and is characterized by psychiatric disorders, motor alterations, and dementia, with the cognitive deficits representing a devastating aspect of the disorder. Oxidative stress and elevated levels of lipid peroxidation (LPO) products are found in mouse models and patients with HD, suggesting that strategies to reduce LPO may be beneficial in HD. In contrast to traditional antioxidants, substituting hydrogen with deuterium at bis-allylic sites in polyunsaturated fatty acids (D-PUFA) decreases the rate-limiting initiation step of PUFA autoxidation, a strategy that has shown benefits in other neurodegenerative diseases...
June 22, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29932276/bccip-binds-to-and-activates-its-promoter-in-a-yy1-dependent-fashion-in-hct116-cells
#12
Yi Sui, Fuqiang Li, Tingting Wu, Jian Ding, Zeming Lu, Lingyao Wang, Yang Yang, Fei Wang, Linhong Zhao, Huihui Zhu, Tao Wei, Jingji Jin, Yong Cai
The restriction of YY1 at BCCIP transcriptional start site (TSS) proximal region in several human cancer cell lines was found by analyzation of ChIP-Seq database from UCSC Genome Browser(h t t p: //genome. ucsc. edu). However, whether the stabilization of YY1 by BCCIP impacts its recruitment in the BCCIP promoter region is unclear. Here, we present evidence that transcriptional regulation of YY1 on BCCIP is closely related to YY1 stability in HCT116 human colon cancer cells. YY1 stabilization was in turn regulated by BCCIP, suggesting the existence of a BCCIP-YY1 feedback loop in regulating BCCIP transcription by the YY1...
June 22, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29931810/a-cu-2-complex-induces-the-aggregation-of-human-papillomavirus-oncoprotein-e6-and-stabilizes-p53
#13
Amit Kumar, Lars T Kuhn, Jochen Balbach
Papillomavirus oncoprotein E6 is a critical factor in the modulation of cervical cancer in humans. At the molecular level, formation of the E6-E6AP-p53 ternary complex, which directs p53's degradation, is the key instigator of cancer transforming properties. Herein, a Cu2+ anthracenyl-terpyridine complex is described which specifically induces the aggregation of E6 in vitro and in cultured cells. For a hijacking mechanism, both E6 and E6AP are required for p53 ubiquitination and degradation. The Cu2+ complex interacts with E6 at the E6AP and p53 binding sites...
June 22, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29931808/claspin-checkpoint-adaptor-and-dna-replication-factor
#14
REVIEW
Veronique A J Smits, Elisa Cabrera, Raimundo Freire, David A Gillespie
Claspin was discovered as a Chk1-interacting protein necessary for Chk1 phosphorylation and activation by the upstream kinase, ATR, in response to DNA synthesis inhibition in Xenopus oocyte extracts. Subsequent investigations have defined a molecular model in which Claspin acts as an adaptor or scaffold protein to facilitate activation of Chk1 by ATR within a multi-protein complex that forms on single-stranded DNA at stalled replication forks and sites of DNA damage. Interestingly, Claspin is an unstable protein whose degradation via the proteasome is tightly regulated via ubiquitination and controlled by multiple ubiquitin ligases and de-ubiquitinases...
June 22, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29931806/the-polypeptide-n-acetylgalactosaminyltransferase-4-exhibits-stage-dependent-expression-in-colorectal-cancer-and-affects-tumorigenesis-invasion-and-differentiation
#15
Xialin Yan, Jishun Lu, Xia Zou, Sen Zhang, Yalu Cui, Leqi Zhou, Feng Liu, Aidong Shan, Jiaoyang Lu, Minghua Zheng, Bo Feng, Yan Zhang
The aberrant expression of mucin-type O-glycosylation plays important roles in the cancer malignancy. Polypeptide N-acetylgalactosaminyltransferases (ppGalNAc-Ts) are a family of conserved enzymes that initiate the mucin-type O-glycosylation in cells. In human, consistent up- or down-regulation of ppGalNAc-Ts expression during the cancer development has been frequently reported. Here, we provide evidence that ppGalNAc-T4 shows a stage-dependent expression at the different stages of colorectal cancer (CRC) in the 62 pair-matched tumor/normal tissues...
June 22, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29924502/crucial-role-of-protein-oligomerization-in-the-pathogenesis-of-alzheimer-s-and-parkinson-s-diseases
#16
REVIEW
Minee L Choi, Sonia Gandhi
Misfolding and aggregation of the proteins amyloid-β (Aβ), tau and alpha-synuclein (α-syn) is the predominant pathology underlying the neurodegenerative disorders, Alzheimer's and Parkinson's disease. Whilst end stage insoluble products of aggregation have been well characterised in human and animal models of disease, accumulating evidence from biophysical, cellular and in vivo studies has shown that soluble intermediates of aggregation, or oligomers, may be the key species that mediate toxicity and underlie seeding and spreading in disease...
June 20, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29923316/endoplasmic-reticulum-quality-control-by-garbage-disposal
#17
Hisae Kadowaki, Hideki Nishitoh
Various types of intracellular and extracellular stresses disturb homeostasis in the endoplasmic reticulum (ER) and, thus, trigger the ER stress response. Unavoidable and/or prolonged ER stress causes cell toxicity and occasionally cell death. The malfunction or death of irreplaceable cells leads to conformational diseases, including diabetes mellitus, ischemic diseases, metabolic diseases, and neurodegenerative diseases. In the past several decades, many studies have revealed the molecular mechanisms of the ER quality control system...
June 19, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29917313/differences-in-substrate-specificity-of-v-cholerae-fabh-enzymes-suggest-new-approaches-for-the-development-of-novel-antibiotics-and-biofuels
#18
Jing Hou, Heping Zheng, Wen-Shyong Tzou, David R Cooper, Maksymilian Chruszcz, Mahendra D Chordia, Keehwan Kwon, Marek Grabowski, Wladek Minor
Vibrio cholerae, the causative pathogen of the life-threatening infection cholera, encodes two copies of β-ketoacyl-ACP synthase III (vcFabH1 and vcFabH2). vcFabH1 and vcFabH2 are pathogenic proteins associated with fatty acid synthesis, lipid metabolism, and potential applications in biofuel production. Our biochemical assays characterize vcFabH1 as exhibiting specificity for acetyl-CoA and CoA thioesters with short acyl chains, similar to that observed for FabH homologs found in most Gram-negative bacteria...
June 19, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29905014/a-crystal-structure-of-coil-1b-of-vimentin-in-the-filamentous-form-provides-a-model-of-a-high-order-assembly-of-a-vimentin-filament
#19
Allan H Pang, Josiah M Obiero, Arkadiusz W Kulczyk, Vitaliy M Sviripa, Oleg V Tsodikov
Vimentin is an intermediate filament (IF) protein that is expressed in leukocytes, fibroblasts and endothelial cells of blood vessels. Vimentin filaments contribute to structural stability of the cell membrane, organelle positioning and protein transport. Vimentin self-assembles into a dimer that subsequently forms high-order structures, including tetramers and octamers. The details of IF assembly at crystallographic resolutions are limited to the tetrameric form. We describe a crystal structure of a fragment of a vimentin rod domain (coil 1B) with a dimer of tetramers in the asymmetric unit...
June 15, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29905002/cancer-the-dark-side-of-wound-healing
#20
REVIEW
Gopinath M Sundaram, Shan Quah, Prabha Sampath
Complex multicellular organisms have evolved sophisticated mechanisms to rapidly resolve epithelial injuries. Epithelial integrity is critical to maintaining internal homeostasis. An epithelial breach represents the potential for pathogen ingress and fluid loss, both of which may have severe consequences if not limited. The mammalian wound healing response involves a finely tuned, self-limiting series of cellular and molecular events orchestrated by the transient activation of specific signalling pathways. Accurate regulation of these events is essential; failure to initiate key steps at the right time delays healing and leads to chronic wounds, while aberrant initiation of wound healing processes may produce cell behaviours that promote cancer progression...
June 15, 2018: FEBS Journal
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