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William R Critchley, Caroline Pellet-Many, Benjamin Ringham-Terry, Michael A Harrison, Ian C Zachary, Sreenivasan Ponnambalam
Receptor tyrosine kinases (RTKs) are membrane-based sensors that enable rapid communication between cells and their environment. Evidence is now emerging that interdependent regulatory mechanisms, such as membrane trafficking, ubiquitination, proteolysis and gene expression, have substantial effects on RTK signal transduction and cellular responses. Different RTKs exhibit both basal and ligand-stimulated ubiquitination, linked to trafficking through different intracellular compartments including the secretory pathway, plasma membrane, endosomes and lysosomes...
March 15, 2018: Cells
Marta Stolarczyk, Bob J Scholte
Chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) share molecular mechanisms that cause the pathological symptoms they have in common. Here, we review evidence suggesting that hyperactivity of the EGFR/ADAM17 axis plays a role in the development of chronic lung disease in both CF and COPD. The ubiquitous transmembrane protease A disintegrin and metalloprotease 17 (ADAM17) forms a functional unit with the EGF receptor (EGFR), in a feedback loop interaction labeled the ADAM17/EGFR axis. In airway epithelial cells, ADAM17 sheds multiple soluble signaling proteins by proteolysis, including EGFR ligands such as amphiregulin (AREG), and proinflammatory mediators such as the interleukin 6 coreceptor (IL-6R)...
2018: Mediators of Inflammation
Eleni C Pappa, Thomas G Bontinis, Maria Tasioula-Margari, John Samelis
The microbiological quality of and changes in the main physicochemical parameters, together with the evolution of proteolysis, lipolysis and volatile profiles of soft Xinotyri, a traditional Greek acid-curd cheese (pH≈4.4, moisture 65%, salt 1%) made from raw (RMC) or pasteurized (PMC) goat's milk without starters, were evaluated during aerobic storage at 4o C for 60 days. No statistically significant differences between the total nitrogen (TN) and nitrogen fraction (% of TN) contents, the degradation of intact αs - or β-caseins, total free amino acid (FAA) contents, and the ratio of hydrophilic and hydrophobic peptides in the water-soluble fraction of RMC and PMC were found...
December 2017: Food Technology and Biotechnology
Lal Sangpuii, Sunil Kumar Dixit, Manoj Kumawat, Shekhar Apoorva, Mukesh Kumar, Deepthi Kappala, Tapas Kumar Goswami, Manish Mahawar
By assisting in the proteolysis, disaggregation and refolding of the aggregated proteins, Caseinolytic proteases (Clps) enhance the cellular survival under stress conditions. In the current study, comparative roles of two such Clps, ClpA (involved in proteolysis) and ClpB (involved in protein disaggregation and refolding) in the survival of Salmonella Typhimurium (S. Typhimurium) under different stresses and in virulence have been investigated. clpA and clpB gene deletion mutant strains (∆clpA and ∆clpB) of S...
March 14, 2018: Scientific Reports
Hsin-Chen Lin, Ching-Ching Yeh, Lo-Yun Chao, Mong-Hsun Tsai, Hung-Hsin Chen, Eric Y Chuang, Liang-Chuan Lai
Hypoxia can lead to solid tumor aggressiveness by driving multiple signaling pathways. Long non-coding RNAs respond to several extrinsic stimuli, causing changes in cancer cells by participating in multiple steps of gene expression. However, genomic profiling of long non-coding RNAs regulated by oxygen in breast cancer remained unclear. Therefore, the aims of this study were to identify oxygen-responsive long non-coding RNAs in breast cancer cells, and to delineate their regulatory mechanisms. The expression profiling of long non-coding RNAs in breast cancer cells growing under normoxic, hypoxic, and re-oxygenated conditions was examined using next-generation sequencing technology...
February 13, 2018: Oncotarget
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
Maria Agthe, Yvonne Garbers, Joachim Grötzinger, Christoph Garbers
BACKGROUND/AIMS: The cytokine interleukin-11 (IL-11) has important pro- and anti-inflammatory functions. It activates its target cells through binding to the IL-11 receptor (IL-11R), and the IL-11/IL-11R complex recruits a homodimer of glycoprotein 130 (gp130). N-linked glycosylation, a post-translational modification where complex oligosaccharides are attached to the side chain of asparagine residues, is often important for stability, folding and biological function of cytokine receptors...
March 7, 2018: Cellular Physiology and Biochemistry
Traci Cramer, Moriah L Penick, Jolena N Waddell, Chris A Bidwell, Yuan H Brad Kim
The objective of this study was to determine associations of small heat shock proteins (sHSPs) in tenderness development of loins from callipyge and normal genotype lambs. Loins (M. longissimus lumborum) from sixteen lambs across four genotypes were collected throughout 9 days of postmortem aging. The loins from callipyge lambs had more intact desmin and troponin T throughout aging periods, as well as less μ-calpain autolysis and more calpastatin compared to loins from other genotypes (P < 0.05). Delayed onset of apoptosis was found in the callipyge loins indicated by less cytochrome c and more inactive procaspase-3 compared to normal lamb loins (P < 0...
March 6, 2018: Meat Science
Massimiliano Magro, Mattia Zaccarin, Giovanni Miotto, Laura Da Dalt, Davide Baratella, Piero Fariselli, Gianfranco Gabai, Fabio Vianello
Surface active maghemite nanoparticles (SAMNs) are able to recognize and bind selected proteins in complex biological systems, forming a hard protein corona. Upon a 5-min incubation in bovine whey from mastitis-affected cows, a significant enrichment of a single peptide characterized by a molecular weight at 4338 Da originated from the proteolysis of aS1 -casein was observed. Notably, among the large number of macromolecules in bovine milk, the detection of this specific peptide can hardly be accomplished by conventional analytical techniques...
March 12, 2018: Analytical and Bioanalytical Chemistry
P Lorenzo Bozzelli, Seham Alaiyed, Eunyoung Kim, Sonia Villapol, Katherine Conant
The perineuronal net (PNN) represents a lattice-like structure that is prominently expressed along the soma and proximal dendrites of parvalbumin- (PV-) positive interneurons in varied brain regions including the cortex and hippocampus. It is thus apposed to sites at which PV neurons receive synaptic input. Emerging evidence suggests that changes in PNN integrity may affect glutamatergic input to PV interneurons, a population that is critical for the expression of synchronous neuronal population discharges that occur with gamma oscillations and sharp-wave ripples...
2018: Neural Plasticity
Miriam Ratliff, Katherine L Hill-Harfe, Elizabeth J Gleason, Huiping Ling, Tim L Kroft, Steven W L'Hernault
Covalent attachment of ubiquitin to substrate proteins changes their function or marks them for proteolysis, and specificity of ubiquitin attachment is mediated by the numerous E3 ligases encoded by animals. Mind Bomb is an essential E3 ligase during Notch pathway signaling in insects and vertebrates. While C. elegans encodes a Mind Bomb homolog ( mib-1 ), it has never been recovered in the extensive Notch suppressor/enhancer screens that have identified numerous pathway components. Here, we show that C. elegans mib-1 null mutants have a spermatogenesis-defective phenotype that results in a heterogeneous mixture of arrested spermatocytes, defective spermatids and motility-impaired spermatozoa...
March 12, 2018: Genetics
Shensen Li, Jianping Mao, Mengjing Wang, Minmin Zhang, Li Ni, Ye Tao, Bihong Huang, Jing Chen
SHPT is one of the most common complications of CKD-MBD. Recent studies indicate that oxyphil cell proliferation is related to SHPT progression, while not inhibited by current treatments. The aim of this study was to analysis the correlation between oxyphil cell and clinical indicators in SHPT, further explore the protein expression differences of oxyphil cell. Among 33 MHD patients, 84.8% patients have one or more oxyphil dominant glands and the overall oxyphil cells proportion was 39.5 ± 16.3%. Univariate correlation and multivariable linear regression analyze showed that oral calcitriol dose and treatment duration were independent indicators of oxyphil cell ratio...
March 8, 2018: Journal of Proteomics
T Porseryd, N Reyhanian Caspillo, K Volkova, L Elabbas, T Källman, P Dinnétz, P-E Olsson, I Porsch-Hällström
17α-Ethinylestradiol (EE2 ) is a ubiquitous aquatic contaminant shown to decrease fish fertility at low concentrations, especially in fish exposed during development. The mechanisms of the decreased fertility are not fully understood. In this study, we perform transcriptome analysis by RNA sequencing of testes from zebrafish with previously reported lowered fertility due to exposure to low concentrations of EE2 during development. Fish were exposed to 1.2 and 1.6 ng/L (measured concentration; nominal concentrations 3 and 10 ng/L) of EE2 from fertilization to 80 days of age, followed by 82 days of remediation in clean water...
March 8, 2018: General and Comparative Endocrinology
Alexey A Konev, Daria V Serebryanaya, Ekaterina V Koshkina, Fedor V Rozov, Vladimir L Filatov, Stanislav V Kozlovsky, Andrey N Kara, Alexey G Katrukha, Alexander B Postnikov
BACKGROUND: N-terminal and C-terminal proteolytic fragments of IGF binding protein 4 (NT-IGFBP-4 and CT-IGFBP-4) were recently shown to predict adverse cardiac events in acute coronary syndrome (ACS) patients. NT-IGFBP-4 and CT-IGFBP-4 are products of the pregnancy-associated plasma protein-A (PAPP-A)-mediated cleavage of IGFBP-4. It has been demonstrated that circulating IGFBP-4 is partially glycosylated in its N-terminal region, although the influence of this glycosylation on PAPP-A-mediated proteolysis and the ratio of glycosylated/non-glycosylated IGFBP-4 fragments in human blood remain unrevealed...
March 8, 2018: Clinical Biochemistry
Natalia Stach, Magdalena Kalinska, Michal Zdzalik, Radoslaw Kitel, Abdulkarim Karim, Karol Serwin, Wioletta Rut, Katrine Larsen, Abeer Jabaiah, Magdalena Firlej, Benedykt Wladyka, Patrick Daugherty, Henning Stennicke, Marcin Drag, Jan Potempa, Grzegorz Dubin
Staphylococcus aureus is a dangerous human pathogen characterized by alarmingly increasing antibiotic resistance. Accumulating evidence suggests the role of Spl proteases in staphylococcal virulence. Spl proteases have restricted, non-overlapping substrate specificity, suggesting that they may constitute a first example of a proteolytic system in bacteria. SplA, SplB, and SplD were previously characterized in terms of substrate specificity and structural determinants thereof. Here we analyze the substrate specificity of SplE documenting its unique P1 preference among Spl proteases and, in fact, among all chymotrypsin-like (family S1) proteases characterized to date...
March 1, 2018: Structure
Juliane Lokau, Christoph Garbers
Interleukin (IL)-11 is a multifunctional cytokine that was traditionally recognized for its hematopoietic and anti-inflammatory functions, but has recently been shown also to be involved in tumorigenesis. IL-11 signaling is initiated by binding of the cytokine to the IL-11 receptor (IL-11R), which is not directly involved in signaling, but required for IL-11 binding to the signal-transducing receptor glycoprotein (gp)130. In classic signaling, IL-11 binds to the membrane-bound IL-11R in order to initiate signal transduction...
March 9, 2018: Journal of Biological Chemistry
Jung Gi Lee, Jae Ha Ryu, Seon-Myung Kim, Moon-Young Park, San-Ho Kim, Young G Shin, Jong-Woo Sohn, Ha Hyung Kim, Zee-Yong Park, Jae Young Seong, Jae Il Kim
Exendin-4, a 39 amino acid peptide isolated from the saliva of the Gila monster, plays an important role in regulating glucose homeostasis, and is used clinically for the treatment of type 2 diabetes. Exendin-4 shares 53% sequence identity with the incretin hormone glucagon-like peptide 1 (GLP-1) but, unlike GLP-1, is highly resistant to proteolytic enzymes such as dipeptidyl peptidase IV (DPP-IV) and neutral endopeptidase 24.11 (NEP 24.11). Herein, we focused on the structure and function of the C-terminal Trp-cage of exendin-4, and suggest that it may be structurally required for resistance to proteolysis by NEP 24...
March 6, 2018: Biochemical Pharmacology
Geetha S Hewawasam, Karthik Dhatchinamoorthy, Mark Mattingly, Chris Seidel, Jennifer L Gerton
Correct localization of the centromeric histone variant CenH3/CENP-A/Cse4 is an important part of faithful chromosome segregation. Mislocalization of CenH3 could affect chromosome segregation, DNA replication and transcription. CENP-A is often overexpressed and mislocalized in cancer genomes, but the underlying mechanisms are not understood. One major regulator of Cse4 deposition is Psh1, an E3 ubiquitin ligase that controls levels of Cse4 to prevent deposition into non-centromeric regions. We present evidence that Chromatin assembly factor-1 (CAF-1), an evolutionarily conserved histone H3/H4 chaperone with subunits shown previously to interact with CenH3 in flies and human cells, regulates Cse4 deposition in budding yeast...
March 7, 2018: Nucleic Acids Research
Sandra Stefanovic-Barrett, Anna S Dickson, Stephen P Burr, James C Williamson, Ian T Lobb, Dick Jh van den Boomen, Paul J Lehner, James A Nathan
Misfolded or damaged proteins are typically targeted for destruction by proteasome-mediated degradation, but the mammalian ubiquitin machinery involved is incompletely understood. Here, using forward genetic screens in human cells, we find that the proteasome-mediated degradation of the soluble misfolded reporter, mCherry-CL1, involves two ER-resident E3 ligases, MARCH6 and TRC8. mCherry-CL1 degradation is routed via the ER membrane and dependent on the hydrophobicity of the substrate, with complete stabilisation only observed in double knockout MARCH6/TRC8 cells...
March 8, 2018: EMBO Reports
Buigues A, Ferrero H, Martínez J, Pellicer N, Pellicer A, Gómez R
To analyze the role of PAI-1 (plasminogen activator inhibitor 1) in endometriotic lesion growth, we studied the effect of PAI-1 inhibition by PAI-039 using a homologous mouse model of endometriosis that allows non-invasive monitoring. Endometrial tissue from donor mice was collected, labeled with mCherry adenovirus, and implanted into a subcutaneous pocket on the ventral abdomen of recipient mice. Seven days after transplantation, mice were randomly allocated in two groups and treated once daily for two weeks with either vehicle (control group) or PAI-1 inhibitor (PAI-039 group)...
March 6, 2018: Biology of Reproduction
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