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Biological Chemistry

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https://www.readbyqxmd.com/read/28095367/micrornas-are-important-regulators-of-drug-resistance-in-colorectal-cancer
#1
Yang Zhang, Jing Wang
Despite of continuous development of cancer treatment over the past decades, drug resistance is still one of the major hurdles of effective therapy for advanced colorectal cancer (CRC) worldwide and the understanding of its underlying mechanisms remains limited. Data which have emerged suggests that many microRNAs (miRNAs) may contribute to drug resistance in CRC. Major findings on miRNA functions in drug resistance of CRC are systemically reviewed here, with the goal of providing new updates to broaden our comprehension of its mechanisms and evidence to utilize miRNAs as potential therapeutic targets for CRC treatment...
February 21, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28214347/involvement-of-the-guanine-nucleotide-exchange-factor-vav3-in-central-nervous-system-development-and-plasticity
#2
Annika Ulc, Christine Gottschling, Ina Schäfer, David Wegrzyn, Simon van Leeuwen, Veronika Luft, Jacqueline Reinhard, Andreas Faissner
Small GTP-hydrolysing enzymes (GTPases) of the RhoA family play manifold roles in cell biology and are regulated by upstream guanine nucleotide exchange factors (GEFs). Herein, we focus on the GEFs of the Vav subfamily. Vav1 was originally described as a protooncogene of the hematopoietic lineage. The GEFs Vav2 and Vav3 are more broadly expressed in various tissues. In particular, the GEF Vav3 may play important roles in the developing nervous system during the differentiation of neural stem cells into the major lineages, namely neurons, oligodendrocytes and astrocytes...
February 18, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28212107/rheb-in-neuronal-degeneration-regeneration-and-connectivity
#3
Veena Nambiar Potheraveedu, Miriam Schöpel, Raphael Stoll, Rolf Heumann
The small GTPase Rheb was originally detected as an immediate early response protein whose expression was induced by NMDA-dependent synaptic activity in the brain. Rheb's activity is highly regulated by its GTPase activating protein (GAP), the tuberous sclerosis complex protein, which stimulates the conversion from the active, GTP-loaded into the inactive, GDP-loaded conformation. Rheb has been established as an evolutionarily conserved molecular switch protein regulating cellular growth, cell volume, cell cycle, autophagy, and amino acid uptake...
February 17, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28141544/the-monoheme-cytochrome-c-subunit-of-alternative-complex-iii-is-a-direct-electron-donor-to-caa3-oxygen-reductase-in-rhodothermus-marinus
#4
Patrícia N Refojo, Filipa Calisto, Miguel A Ribeiro, Miguel Teixeira, Manuela M Pereira
No abstract text is available yet for this article.
January 31, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28141543/molecular-challenges-imposed-by-mhc-i-restricted-long-epitopes-on-t-cell-immunity
#5
Tracy M Josephs, Emma J Grant, Stephanie Gras
It has widely been accepted that major histocompatibility complex class I molecules (MHC-I) are limited to binding small peptides of 8 to 10 residues in length. However, this dogma has recently been challenged with the identification of longer peptides (≥11 residues) that can also elicit cytotoxic CD8+ T cell responses. Indeed, a growing number of studies demonstrate that these non-canonical epitopes are important targets for the immune system. As long epitopes represent up to 10% of the peptide repertoire bound to MHC-I molecules, here we review their impact on antigen presentation by MHC-I, TCR recognition, and T cell immunity...
January 31, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28141542/kinetic-characterization-of-apoptotic-ras-signalling-through-nore1-mst1-complex-formation
#6
Agne Koturenkiene, Cihan Makbul, Christian Herrmann, Diana Constantinescu-Aruxandei
The Ras-mediated apoptotic signaling is expected to be mediated via Rassf-MST complexes, but the system has been poorly characterized in vitro until now. Here we demonstrate that active H-Ras, Nore1A and MST1 form a stable ternary complex in vitro without other external factors, Nore1A interacting simultaneously with H-Ras and MST1 via its RBD and SARAH domain, respectively. Moreover, our data show for the first time that the SARAH domain of Nore1A plays a role in the Nore1A binding to H-Ras. Finally, we analyse the relation between the electrostatic and hydrophobic forces and kinetic constants of the Nore1A - H-Ras complex...
January 28, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28095368/iron-overload-and-altered-iron-metabolism-in-ovarian-cancer
#7
Stephanie Rockfield, Joseph Raffel, Radhe Mehta, Nabila Rehman, Meera Nanjundan
Iron is an essential element required for many processes within the cell. Dysregulation in iron homeostasis due to iron overload is detrimental. This nutrient is postulated to contribute to the initiation of cancer; however, the mechanisms by which this occurs remain unclear. Defining how iron promotes the development of ovarian cancers from precursor lesions is essential for developing novel therapeutic strategies. In this review, we discuss (1) how iron overload conditions may initiate ovarian cancer development, (2) dysregulated iron metabolism in cancers, (3) the interplay between bacteria, iron, and cancer, and (4) chemotherapeutic strategies targeting iron metabolism in cancer patients...
January 14, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28085670/when-how-and-why-regulated-proteolysis-by-the-essential-ftsh-protease-in-escherichia-coli
#8
Lisa-Marie Bittner, Jan Arends, Franz Narberhaus
Cellular proteomes are dynamic and adjusted to permanently changing conditions by ATP-fueled proteolytic machineries. Among the five AAA+ proteases in Escherichia coli FtsH is the only essential and membrane-anchored metalloprotease. FtsH is a homohexamer that uses its ATPase domain to unfold and translocate substrates that are subsequently degraded without the need of ATP in the proteolytic chamber of the protease domain. FtsH eliminates misfolded proteins in the context of general quality control and properly folded proteins for regulatory reasons...
January 13, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/27935845/stability-and-aggregation-propensity-do-not-fully-account-for-the-association-of-various-germline-variable-domain-gene-segments-with-light-chain-amyloidosis
#9
Sergio A Garay Sánchez, Francisco Javier Rodríguez Álvarez, Guadalupe Zavala-Padilla, Luz María Mejia-Cristobal, Armando Cruz-Rangel, Miguel Costas, D Alejandro Fernández Velasco, Jorge Melendez-Zajgla, Luis Del Pozo-Yauner
Variable domain (VL) gene segments exhibit variable tendencies to be associated with light chain amyloidosis (AL). While few of them are very frequent in AL and give rise to most of the amyloidogenic light chains compiled at the sequence databases, other are rarely found among the AL cases. To analyze to which extent these tendencies depend on folding stability and aggregation propensity of the germline VL protein, we characterized VL proteins encoded by four AL-associated germline gene segments and one not associated to AL...
January 13, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/27926477/intra-or-extra-exosomal-secretion-of-hdgf-isoforms-the-extraordinary-function-of-the-hdgf-a-n-terminal-peptide
#10
Jessica Nüße, Eva-Maria Blumrich, Ursula Mirastschijski, Lennart Kappelmann, Sørge Kelm, Frank Dietz
Hepatoma-derived growth factor (HDGF) is a protein with diverse intracellular functions. Moreover, after non-conventional secretion, extracellular HDGF is able to influence different signaling pathways, leading for example to induction of processes like epithelial-mesenchymal transition (EMT) and cell migration. Intriguingly, in recent proteome studies, HDGF was also found secreted by special microvesicles called exosomes. Recently, we demonstrated the existence of two new HDGF isoforms (B and C). These isoforms are involved in different cellular processes than HDGF-A...
January 13, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/27926476/mitochondrial-cytochrome-c-oxidase-is-inhibited-by-atp-only-at-very-high-atp-adp-ratios
#11
Rabia Ramzan, Andreas K Schaper, Petra Weber, Annika Rhiel, Muhammad Saad Siddiq, Sebastian Vogt
In the past, divergent results have been reported based on different methods and conditions used for enzymatic activity measurements of cytochrome c oxidase (CytOx). Here, we analyze in detail and show comparable and reproducible polarographic activity measurements of ATP-dependent inhibition of CytOx kinetics in intact and non-intact rat heart mitochondria and mitoplasts. We found that this mechanism is always present in isolated rat heart mitochondria and mitoplasts; however, it is measurable only at high ATP/ADP ratios using optimal protein concentrations...
January 13, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/27902449/is-n-n-dimethylglycine-n-oxide-a-choline-and-betaine-metabolite
#12
Michael Lever, Christopher J McEntyre, Peter M George, Stephen T Chambers
Choline metabolism is by oxidation to betaine, which is demethylated to N,N-dimethylglycine; dimethylglycine is oxidatively demethylated to sarcosine. This pathway is important for osmoregulation and as a source of methyl groups. We asked whether another metabolite was involved. We synthesized the N-oxide of dimethylglycine (DMGO) by oxidizing dimethylglycine with peracetic acid, and measured DMGO in human plasma and urine by HPLC-MS/MS with positive ion detection, using two chromatography procedures, based on ion exchange and HILIC separations...
January 13, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28076289/from-bacteria-to-chloroplasts-evolution-of-the-chloroplast-srp-system
#13
Dominik Ziehe, Beatrix Dünschede, Danja Schünemann
Chloroplasts derive from a prokaryotic symbiont that lost most of its genes during evolution. As a result, the great majority of chloroplast proteins are encoded in the nucleus and are posttranslationally imported into the organelle. The chloroplast genome encodes only a few proteins. These include several multispan thylakoid membrane proteins which are synthesized on thylakoid-bound ribosomes and cotranslationally inserted into the membrane. During evolution, ancient prokaryotic targeting machineries were adapted and combined with novel targeting mechanisms to facilitate post- and cotranslational protein transport in chloroplasts...
January 10, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/27935848/plasmin-ogen-serves-as-a-favorable-biomarker-for-prediction-of-survival-in-advanced-high-grade-serous-ovarian-cancer
#14
Shuo Zhao, Julia Dorn, Rudolf Napieralski, Axel Walch, Sandra Diersch, Matthias Kotzsch, Nancy Ahmed, John D Hooper, Marion Kiechle, Manfred Schmitt, Viktor Magdolen
In serous ovarian cancer, the clinical relevance of tumor cell-expressed plasmin(ogen) (PLG) has not yet been evaluated. Due to its proteolytic activity, plasmin supports tumorigenesis, however, angiostatin(-like) fragments, derived from PLG, can also function as potent anti-tumorigenic factors. In the present study, we assessed PLG protein expression in 103 cases of advanced high-grade serous ovarian cancer (FIGO III/IV) by immunohistochemistry (IHC). In 70/103 cases, positive staining of tumor cells was observed...
January 6, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28051995/in-vitro-modelling-of-familial-amyloidotic-polyneuropathy-allows-quantitative-detection-of-transthyretin-amyloid-fibril-like-structures-in-hepatic-derivatives-of-patient-specific-induced-pluripotent-stem-cells
#15
Jeannine Hoepfner, Mandy Kleinsorge, Oliver Papp, Susanne Alfken, Robin Heiringhoff, Andreas Pich, Vanessa Sauer, Andree Zibert, Gudrun Göhring, Hartmut Schmidt, Malte Sgodda, Tobias Cantz
The transthyretin protein is thermodynamically destabilised by mutations in the transthyretin gene, promoting the formation of amyloid fibrils in various tissues. Consequently, impaired autonomic organ function is observed in patients suffering from transthyretin-related Familial Amyloidotic Polyneuropathy (FAP). The influence of individual genetic backgrounds on fibril formation as a potential cause of genotype-phenotype variations needs to be investigated in order to ensure efficient patient-specific therapies...
January 4, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/27865090/characterization-of-the-subcellular-localization-and-nuclear-import-molecular-mechanisms-of-herpes-simplex-virus-1-ul2
#16
Mingsheng Cai, Zebin Huang, Zongmin Liao, Tao Chen, Ping Wang, Si Jiang, Daixiong Chen, Tao Peng, Yun Bian, Gengde Hong, Hang Yang, Zhancheng Zeng, Xiaowei Li, Meili Li
As a crucial protein, the herpes simplex virus 1 (HSV-1) UL2 protein has been shown to take part in various stages of viral infection, nonetheless, its exact subcellular localization and transport molecular determinants are not well known thus far. In the present study, by using live cells fluorescent microscopy assay, UL2 tagged with enhanced yellow fluorescent protein was transiently expressed in live cells and showed a completely nuclear accumulation without the presence of other HSV-1 proteins. Moreover, the nuclear transport of UL2 was characterized to be assisted by multiple transport pathways through Ran-, importin α1-, α5-, α7-, β1- and transportin-1 cellular transport receptors...
December 28, 2016: Biological Chemistry
https://www.readbyqxmd.com/read/27845877/substrate-processing-in-intramembrane-proteolysis-by-%C3%AE-secretase-the-role-of-protein-dynamics
#17
Dieter Langosch, Harald Steiner
Intramembrane proteases comprise a number of different membrane proteins with different types of catalytic sites. Their common denominator is cleavage within the plane of the membrane, which usually results in peptide bond scission within the transmembrane helices of their substrates. Despite recent progress in the determination of high-resolution structures, as illustrated here for the γ-secretase complex and its substrate C99, it is still unknown how these enzymes function and how they distinguish between substrates and non-substrates...
December 28, 2016: Biological Chemistry
https://www.readbyqxmd.com/read/28002022/interface-analysis-of-small-gtp-binding-protein-complexes-suggests-preferred-membrane-orientations
#18
Ingrid R Vetter
Crystal structures of small GTP binding protein complexes with their effectors and regulators reveal that one particularly flat side of the G domain that contains helix α4 and the C-terminal helix α5 is practically devoid of contacts. Although this observation seems trivial since the main binding targets are the switch I and II regions opposite of this side, the fact that all interacting proteins, even the largest ones, seem to avoid occupying this area (except for Ran, that does not localize to membranes) is quite striking...
December 21, 2016: Biological Chemistry
https://www.readbyqxmd.com/read/28002019/lysosomes-in-programmed-cell-death-pathways-from-initiators-to-amplifiers
#19
Nežka Kavčič, Katarina Pegan, Boris Turk
Lysosome is the central organelle for intracellular degradation of biological macromolecules and organelles. The material destined for degradation enters the lysosomes primarily via endocytosis, autophagy and phagocytosis, and is degraded through the concerted action of more than 50 lysosomal hydrolases. However, lysosomes are also linked with numerous other processes, including cell death, inflammasome activation and immune response, as well as with lysosomal secretion and cholesterol recycling. Among them programmed cell death pathways including apoptosis have received major attention...
December 21, 2016: Biological Chemistry
https://www.readbyqxmd.com/read/27935847/structure-based-development-of-pde%C3%AE-inhibitors
#20
Pablo Martín-Gago, Eyad Kalawy Fansa, Alfred Wittinghofer, Herbert Waldmann
The prenyl binding protein PDEδ enhances the diffusion of farnesylated Ras proteins in the cytosol, ultimately affecting their correct localization and signaling. This has turned PDEδ into a promising target to prevent oncogenic KRas signaling. In this review we summarize and describe the structure-guided-development of the three different PDEδ inhibitor chemotypes that have been documented so far. We also compare both their potency for binding to the PDEδ pocket and their in vivo efficiency in suppressing oncogenic KRas signaling, as a result of the inhibition of the PDEδ/KRas interaction...
December 21, 2016: Biological Chemistry
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