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Protein turnover

Jianjun Chang, Yan Ding, Zhiyu Zhou, Hong-Guang Nie, Hong-Long Ji
Transepithelial fluid and salt re-absorption in epithelial tissues play an important role in fluid and salt homeostasis. In absorptive epithelium, fluid and salt flux is controlled by machinery mainly composed of epithelial sodium channels (ENaC), cystic fibrosis transmembrane conductance regulator (CFTR), Na⁺/H⁺ exchanger (NHE), aquaporin, and sodium potassium adenosine triphosphatase (Na⁺/K⁺-ATPase). Dysregulation of fluid and salt transport across epithelium contributes to the pathogenesis of many diseases, such as pulmonary edema and cystic fibrosis...
March 16, 2018: International Journal of Molecular Sciences
Lan Hai, Maria M Szwarc, Bin He, David M Lonard, Ramakrishna Kommagani, Francesco J DeMayo, John P Lydon
Speckle-type poz protein (SPOP) is an E3-ubiquitin ligase adaptor for turnover of a diverse number of proteins involved in key cellular processes from chromatin remodeling, transcriptional regulation to cell signaling. Genomic analysis revealed that SPOP somatic mutations are found in a subset of endometrial cancers, suggesting that these mutations act as oncogenic drivers of this gynecologic malignancy. These studies also raise the question as to the role of wild type SPOP in normal uterine function. To address this question, we generated a mouse model (Spopd/d) in which SPOP is ablated in uterine cells that express the PGR...
March 13, 2018: Biology of Reproduction
Peter L Cummins, Babu Kannappan, Jill E Gready
The ubiquitous enzyme Ribulose 1,5-bisphosphate carboxylase-oxygenase (RuBisCO) fixes atmospheric carbon dioxide within the Calvin-Benson cycle that is utilized by most photosynthetic organisms. Despite this central role, RuBisCO's efficiency surprisingly struggles, with both a very slow turnover rate to products and also impaired substrate specificity, features that have long been an enigma as it would be assumed that its efficiency was under strong evolutionary pressure. RuBisCO's substrate specificity is compromised as it catalyzes a side-fixation reaction with atmospheric oxygen; empirical kinetic results show a trend to tradeoff between relative specificity and low catalytic turnover rate...
2018: Frontiers in Plant Science
Yong Li, Peggy Sekula, Matthias Wuttke, Judith Wahrheit, Birgit Hausknecht, Ulla T Schultheiss, Wolfram Gronwald, Pascal Schlosser, Sara Tucci, Arif B Ekici, Ute Spiekerkoetter, Florian Kronenberg, Kai-Uwe Eckardt, Peter J Oefner, Anna Köttgen
Background The kidneys have a central role in the generation, turnover, transport, and excretion of metabolites, and these functions can be altered in CKD. Genetic studies of metabolite concentrations can identify proteins performing these functions. Methods We conducted genome-wide association studies and aggregate rare variant tests of the concentrations of 139 serum metabolites and 41 urine metabolites, as well as their pairwise ratios and fractional excretions in up to 1168 patients with CKD. Results After correction for multiple testing, genome-wide significant associations were detected for 25 serum metabolites, two urine metabolites, and 259 serum and 14 urinary metabolite ratios...
March 15, 2018: Journal of the American Society of Nephrology: JASN
Paul Glendenning, S A Paul Chubb, Samuel Vasikaran
Bone turnover marker (BTM's) concentrations in blood and urine reflect bone-remodelling activity, and may be useful adjuncts in the diagnosis and management of metabolic bone diseases. Newer biomarkers, mainly bone regulatory proteins, are currently being investigated to elucidate their role in bone metabolism and disease and may in future be useful in clinical diagnosis and management of metabolic bone disease. BTM concentrations increase around menopause in women, and at a population level the degree of increase in BTM's reflect bone loss...
March 12, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
Janaina de Freitas Nascimento, Steven Kelly, Jack Sunter, Mark Carrington
Selective transcription of individual protein coding genes does not occur in trypanosomes and the cellular copy number of each mRNA must be determined post-transcriptionally. Here, we provide evidence that codon choice directs the levels of constitutively expressed mRNAs. First, a novel codon usage metric, the gene expression codon adaptation index (geCAI), was developed that maximised the relationship between codon choice and the measured abundance for a transcriptome. Second, geCAI predictions of mRNA levels were tested using differently coded GFP transgenes and were successful over a 25-fold range, similar to the variation in endogenous mRNAs...
March 15, 2018: ELife
Christopher Wass, Bruno Sauce, Alessandro Pizzo, Louis D Matzel
In both humans and mice, performance on tests of intelligence or general cognitive ability (GCA) is related to dopamine D1 receptor-mediated activity in the prelimbic cortex, and levels of DRD1 mRNA predict the GCA of mice. Here we assessed the turnover rate of D1 receptors as well as the expression level of the D1 chaperone protein (DRiP78) in the medial PPC (mPFC) of mice to determine whether rate of receptor turnover was associated with variations in the GCA of genetically heterogeneous mice. Following assessment of GCA (aggregate performance on four diverse learning tests) mice were administered an irreversible dopamine receptor antagonist (EEDQ), after which the density of new D1 receptors were quantified...
March 14, 2018: Scientific Reports
Nathan Zuzow, Arit Ghosh, Marilyn Leonard, Jeffrey Liao, Bing Yang, Eric J Bennett
Previous genetic and biochemical studies from S. cerevisiae have identified a critical ribosome-associated quality control complex (RQC) that facilitates resolution of stalled ribosomal complexes. While components of the mammalian RQC have been examined in vitro , a systematic characterization of RQC protein interactions in mammalian cells has yet to be described. Here, we utilize both proximity-labeling proteomic approaches, BioID and APEX, and traditional affinity-based strategies to both identify interacting proteins of mammalian RQC members and putative substrates for the RQC resident E3 ligase, Ltn1...
March 14, 2018: Molecular Biology of the Cell
Miwa Isshiki, Satoshi Hirayama, Tsuyoshi Ueno, Masayuki Ito, Ayaka Furuta, Kouji Yano, Kotoko Yamatani, Masami Sugihara, Mayumi Idei, Takashi Miida
BACKGROUND: Rapid turnover proteins (RTPs), such as transthyretin (TTR), retinol binding protein (RBP), and transferrin (Tf), provide an accurate assessment of nutritional status but are susceptible to inflammation. Lipid-related markers, which have short half-lives in serum, may be better suited for nutritional assessment. We sought to identify sensitive nutritional markers unaffected by inflammation. METHODS: Fasting serum samples were collected from 30 malnourished inpatients and 25 healthy volunteers...
March 11, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
Daniel L Kiss, William D Baez, Kay Huebner, Ralf Bundschuh, Daniel R Schoenberg
OBJECTIVES: In > 50% of cancers tumor development involves the early loss of Fhit (fragile histidine triad) protein expression, yet the mechanistic pathway(s) by which Fhit mediates its tumor suppressor functions are not fully understood. Earlier attempts to identify a Fhit-deficient gene expression profile relied on total cellular RNA and microarray analysis. The data here used RNA sequencing (RNA-Seq) of Fhit-negative and Fhit-positive cells as proof of principle for the impact of Fhit on specific mRNAs, and to lay the foundation for a study using ribosome profiling to identify mRNAs whose translation is affected by FHIT loss...
March 14, 2018: BMC Research Notes
Heather Flanagan-Steet, Courtney Christian, Po-Nien Lu, Megan Aarnio-Peterson, Laura Sanman, Stephanie Archer-Hartmann, Parastoo Azadi, Matthew Bogyo, Richard A Steet
Cysteine cathepsins play roles during development and disease beyond their function in lysosomal protein turnover. Here, we leverage a fluorescent activity-based probe (ABP), BMV109, to track cysteine cathepsins in normal and diseased zebrafish embryos. Using this probe in a model of mucolipidosis II, we show that loss of carbohydrate-dependent lysosomal sorting alters the activity of several cathepsin proteases. The data support a pathogenic mechanism where TGF-ß signals enhance the proteolytic processing of pro-Ctsk by modulating the expression of chondroitin 4-sulfate (C4-S)...
March 13, 2018: Cell Reports
Qing-Long Wang, Juan-Hua Chen, Ning-Yu He, Fang-Qing Guo
Increases in ambient temperatures have been a severe threat to crop production in many countries around the world under climate change. Chloroplasts serve as metabolic centers and play a key role in physiological adaptive processes to heat stress. In addition to expressing heat shock proteins that protect proteins from heat-induced damage, metabolic reprogramming occurs during adaptive physiological processes in chloroplasts. Heat stress leads to inhibition of plant photosynthetic activity by damaging key components functioning in a variety of metabolic processes, with concomitant reductions in biomass production and crop yield...
March 14, 2018: International Journal of Molecular Sciences
Antonella Sesta, Maria Francesca Cassarino, Francesco Cavagnini, Francesca Pecori Giraldi
PURPOSE: A large number of studies has investigated proopiomelanocortin processing in anterior pituitary corticotropes but little is known on proopiomelanocortin/ACTH degradation within these cells. The ubiquitin-proteasome system is an intracellular protein degradation pathway which has garnered considerable interest in recent times, given its role in maintenance of protein homeostasis. Aim of the present study was to evaluate the role of the ubiquitin-proteasome system in proopiomelanocortin/ACTH turnover in pituitary corticotropes...
March 13, 2018: Endocrine
Melissa Conte, Josselin Lupette, Khawla Seddiki, Coline Meï, Lina J Dolch, Valerie Gros, Caroline Barette, Fabrice Rébeillé, Juliette Jouhet, Eric Marechal
Microalgae are a promising feedstock for the production of triacylglycerol (TAG) for a variety of potential applications, ranging from food and human health to biofuels and green chemistry. However, obtaining high TAG yields is challenging. A phenotypic assay for accumulation of oil droplets was developed to screen a library of 1,200 drugs, annotated with pharmacology information, to select compounds that trigger TAG accumulation in the diatom Phaeodactylum. Using this screen, we identified 34 molecules acting in a dose-dependent manner...
March 13, 2018: Plant Physiology
X Chen, X Y Li, M Long, X Wang, Z W Gao, Y Cui, J Ren, Z Zhang, C Liu, K Dong, H Zhang
Metadherin (MTDH) is an oncoprotein and is expressed at high levels in a wide variety of human carcinomas, which represents an important genetic determinant and regulates multiple events in tumorigenesis. MTDH promotes breast cancer cell proliferation and tumorigenesis through the activation of numerous signaling pathways. Currently, the mecha- nism regulating MTDH expression is poorly understood. Here we identified that FBXW7, a component of E3 ubiquitin ligase, targets MTDH for ubiquitin-mediated degradation...
2018: Neoplasma
Masanori Izumi, Sakuya Nakamura
Most assimilated nutrients in the leaves of land plants are stored in chloroplasts as photosynthetic proteins, where they mediate CO₂ assimilation during growth. During senescence or under suboptimal conditions, chloroplast proteins are degraded, and the amino acids released during this process are used to produce young tissues, seeds, or respiratory energy. Protein degradation machineries contribute to the quality control of chloroplasts by removing damaged proteins caused by excess energy from sunlight...
March 12, 2018: International Journal of Molecular Sciences
A Mostek, M Slowinska, S Judycka, H Karol, A Ciereszko, M A Dietrich
During semen cryopreservation, spermatozoa are exposed to physical and chemical stressors that result in their functional and structural damage. Growing evidence suggests that most cryoinjuries result from oxidative stress accompanying sperm cryopreservation. Elevated amounts of reactive oxygen species (ROS) generated during cryopreservation can react with sperm macromolecules, including proteins. The goal of this study was to investigate the oxidative modifications (measured as carbonylation level changes) of carp spermatozoa proteins triggered by the cryopreservation process...
March 9, 2018: Journal of Animal Science
Haim Yuval Aviram, Menahem Pirchi, Hisham Mazal, Yoav Barak, Inbal Riven, Gilad Haran
The functional cycle of many proteins involves large-scale motions of domains and subunits. The relation between conformational dynamics and the chemical steps of enzymes remains under debate. Here we show that in the presence of substrates, domain motions of an enzyme can take place on the microsecond time scale, yet exert influence on the much-slower chemical step. We study the domain closure reaction of the enzyme adenylate kinase from Escherichia coli while in action (i.e., under turnover conditions), using single-molecule FRET spectroscopy...
March 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
Angelina D Schoenenberger, Jasper Foolen, Pascal Moor, Unai Silvan, Jess G Snedeker
Healthy tendon tissue features a highly aligned extracellular matrix that becomes disorganized with disease. Recent evidence suggests that inflammation coexists with early degenerative changes in tendon, and that crosstalk between immune-cells and tendon fibroblasts (TFs) can contribute to poor tissue healing. We hypothesized that a disorganized tissue architecture may predispose tendon cells to degenerative extracellular matrix remodeling pathways, particularly within a pro-inflammatory niche. This hypothesis was tested by analyzing human TFs cultured on electrospun polycaprolactone (PCL) mats with either highly aligned or randomly oriented fiber structures...
March 9, 2018: Acta Biomaterialia
Hessam Sepasi Tehrani, Ali Akbar Moosavi-Movahedi
Catalase is one of the firsts in every realm of biological sciences. At the same time it also has a number of unusual features. It has one of the highest turnovers numbers of any enzymes. It is essential for neutralizing the noxious hydrogen peroxide both in the nature and the various industries such as dairy, textile and pharmaceutics. It also has the merit of being one of the first protein crystals to be isolated. Ironically its three-dimensional structure was discerned some forty years later. However through the times this senile enzyme has continued to intrigue the scientists by surprising facts and phenomena, such as peculiar interweaving of subunits and remarkable thermal stability...
March 9, 2018: Progress in Biophysics and Molecular Biology
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