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Annick Renevey, Sereina Riniker
Polytheonamide B (pTB), a highly cytotoxic peptide produced by a symbiotic bacterium of the marine sponge Theonella swinhoei, forms a transmembrane pore consisting of 49 residues. More than half of its residues are posttranslationally modified. Epimerizations result in alternating L- and D-amino acids that allow the peptide to adopt a [Formula: see text]-helical conformation. Unusually, the wide [Formula: see text]-helix of pTB is stable in a polar environment, which is in contrast to gramicidin A, an antibiotic with similar function and structure...
October 15, 2016: European Biophysics Journal: EBJ
Ximena Zottig, Mathieu Laporte Wolwertz, Makan Golizeh, Leanne Ohlund, Lekha Sleno, Steve Bourgault
Light chain amyloidosis (AL) originates from the deposition of immunoglobulin light chains (LCs) as amyloid fibrils in the extracellular space of vital organs. Although non-enzymatic post-translational modifications (PTMs) have been shown to contribute to protein misfolding diseases, little is known about their contributions to LC amyloidogenicity. In this study, we investigated the effects of three oxidative PTMs, carbonylation by hydroxynonenal (HNE), oxidation and nitration, on the structure, thermodynamic stability and self-assembly propensity of a LC variable domain from the λ6 germline, Wil...
October 11, 2016: Biophysical Chemistry
Inês M Luís, Bruno M Alexandre, M Margarida Oliveira, Isabel A Abreu
Often plant tissues are recalcitrant and, due to that, methods relying on protein precipitation, such as TCA/acetone precipitation and phenol extraction, are usually the methods of choice for protein extraction in plant proteomic studies. However, the addition of precipitation steps to protein extraction methods may negatively impact protein recovery, due to problems associated with protein re-solubilization. Moreover, we show that when working with non-recalcitrant plant tissues, such as young maize leaves, protein extraction methods with precipitation steps compromise the maintenance of some labile post-translational modifications (PTMs), such as phosphorylation...
2016: PloS One
Xiao Zou, Michael Blank
The p38 MAPK signaling pathway is a key signal transduction cascade that cancer cells employ to sense and adapt to a plethora of environmental stimuli, and has attracted much attention as a promising target for cancer therapy. Accumulating evidence suggests a dual role of p38 signaling in various types of cancers, wherein the p38 pathway can both suppress and promote tumor growth, metastasis and chemoresistance. This dual role of p38 signaling, along with its context dependence and versatility, poses a great challenge for developing efficient anticancer treatment...
October 8, 2016: Cancer Letters
Atefeh Rabiee, Veit Schwämmle, Simone Sidoli, Jie Dai, Adelina Rogowska-Wrzesinska, Susanne Mandrup, Ole N Jensen
Mass spectrometry (MS) based quantitative proteomics and phosphoproteomics applied to monitor the alteration of nuclear proteins during the early stages (4 hours) of preadipocyte differentiation. A total of 4072 proteins including 2434 phosphorylated proteins identified, a majority of which were assigned as regulators of gene expression. Among 288 identified transcriptional regulators, 49 were regulated within four hours of adipogenic stimulation including several known and many novel potential adipogenic regulators...
September 26, 2016: Proteomics
Zhongwei Li, Pingfu Hou, Dongmei Fan, Meichen Dong, Musong Ma, Hongyuan Li, Ruosi Yao, Yuxin Li, Guannan Wang, Pengyu Geng, Adhanom Mihretab, Dongxu Liu, Yu Zhang, Baiqu Huang, Jun Lu
EZH2 (the Enhancer of Zeste Homolog 2), as a key epigenetic regulator and EMT inducer, participates in a variety of cancer metastasis. EZH2 stability is regulated by several types of post-translational modifications (PTMs).The long non-coding RNAs (lncRNA) have been implicated to have critical roles in multiple carcinogenesis through a wide range of mechanisms, including modulating the stability of proteins. To date, whether the stability of EZH2 protein is regulated by lncRNAs remains unexplored. Here we report the discovery of ANCR modulating the stability of EZH2, and hence in the invasion and metastasis of breast cancer cells...
October 7, 2016: Cell Death and Differentiation
Michael D Hebert, Aaron R Poole
The biogenesis of small nuclear ribonucleoproteins (snRNPs), small Cajal body-specific RNPs (scaRNPs), small nucleolar RNPs (snoRNPs) and the telomerase RNP involves Cajal bodies (CBs). Although many components enriched in the CB contain post-translational modifications (PTMs), little is known about how these modifications impact individual protein function within the CB and, in concert with other modified factors, collectively regulate CB activity. Since all components of the CB also reside in other cellular locations, it is also important that we understand how PTMs affect the subcellular localization of CB components...
October 7, 2016: RNA Biology
J Bobrowska, J Moffat, K Awsiuk, J Pabijan, J Rysz, A Budkowski, M Reading, M Lekka
Various techniques have been already reported to differentiate between normal (non-malignant) and cancerous cells based on their physico-chemical properties. This is relatively simple when studied cancerous cells originate from distant stages of cancer progression. Here, studies on chemical properties of two closely related human melanoma cell lines are presented: WM115 melanoma cells were taken from the vertical growth phase while WM266-4 from the skin metastatic site of the same patient. Their chemical properties were studied by two techniques, namely time-of-flight secondary ion mass spectra (ToF SIMS) and photothermal microspectroscopy (PTMS), used to record mass and photothermal spectra of cells, respectively...
September 16, 2016: Analyst
Nannan Tang, Zhaoxin Li, Limin Yang, Qiuquan Wang
Low-abundance tyrosine phosphorylation is crucial to not only normal but also aberrant life processes. We designed and synthesized a photocleavable magnetic nanoparticle-based gallium tag for tagging and enrichment as well as UV-release of the phosphate-bearing molecules/ions in cells. HPLC/(71)Ga species-unspecific isotope dilution ((71)Ga-SUID) ICP-MS was subsequently developed for specific and absolute quantification of phosphotyrosine (pY) under the assistance of a protein tyrosine phosphatase-1B (PTP-1B)...
October 4, 2016: Analytical Chemistry
Jai Shankar Singh, Vaibhav Kumar Shukla, Mansi Gujrati, Ram Kumar Mishra, Ashutosh Kumar
One of the most debilitating diseases Malaria, in its different forms, is caused by protozoan of Plasmodium species. Deadliest among these forms is the "cerebral malaria" which is afflicted upon by Plasmodium falciparum. Plasmodium adopts numerous strategies including various post-translational modifications (PTMs) to infect and survive in the human host. These PTMs have proven their critical requirement in the Plasmodium biology. Recently, sumoylation has been characterized as one of the important PTMs and many of its putative substrates have been identified in Plasmodium...
October 3, 2016: Biomolecular NMR Assignments
Bin Song, Juan Du, Ye Feng, Yong-Jian Gao, Ji-Sheng Zhao
The aim of the present study was to investigate the mechanisms of long non-coding RNAs (lncRNAs) in a gastric cancer cell line treated with celecoxib. The human gastric carcinoma cell line NCI-N87 was treated with 15 µM celecoxib for 72 h (celecoxib group) and an equal volume of dimethylsulfoxide (control group), respectively. Libraries were constructed by NEBNext Ultra RNA Library Prep kit for Illumina. Paired-end RNA sequencing reads were aligned to a human hg19 reference genome using TopHat2. Differentially expressed genes (DEGs) and lncRNAs were identified using Cuffdiff...
October 2016: Experimental and Therapeutic Medicine
Johnathan Neiswinger, Ijeoma Uzoma, Eric Cox, HeeSool Rho, Jun Seop Jeong, Heng Zhu
Protein microarray technology provides a straightforward yet powerful strategy for identifying substrates of posttranslational modifications (PTMs) and studying the specificity of the enzymes that catalyze these reactions. Protein microarray assays can be designed for individual enzymes or a mixture to establish connections between enzymes and substrates. Assays for four well-known PTMs-phosphorylation, acetylation, ubiquitylation, and SUMOylation-have been developed and are described here for use on functional protein microarrays...
October 3, 2016: Cold Spring Harbor Protocols
Matthew Torres, Henry Dewhurst, Niveda Sundararaman
Post-translational modifications (PTMs) regulate protein behavior through modulation of protein-protein interactions, enzymatic activity, and protein stability essential in the translation of genotype to phenotype in eukaryotes. Currently, less than 4% of all eukaryotic PTMs are reported to have biological function &- a statistic that continues to decrease with an increasing rate of PTM detection. Previously, we developed SAPH-ire (Structural Analysis of PTM Hotspots) &- a method for the prioritization of PTM function potential that has been used effectively to reveal novel PTM regulatory elements in discrete protein families (Dewhurst et al...
October 3, 2016: Molecular & Cellular Proteomics: MCP
Nadav Brandes, Dan Ofer, Michal Linial
Determining residue-level protein properties, such as sites of post-translational modifications (PTMs), is vital to understanding protein function. Experimental methods are costly and time-consuming, while traditional rule-based computational methods fail to annotate sites lacking substantial similarity. Machine Learning (ML) methods are becoming fundamental in annotating unknown proteins and their heterogeneous properties. We present ASAP (Amino-acid Sequence Annotation Prediction), a universal ML framework for predicting residue-level properties...
2016: Database: the Journal of Biological Databases and Curation
Hana Stiborova, Michal Kolar, Jana Vrkoslavova, Jana Pulkrabova, Jana Hajslova, Katerina Demnerova, Ondrej Uhlik
Obtaining a complex picture of how pollutants synergistically influence toxicity of a system requires statistical correlation of chemical and ecotoxicological data. In this study, we determined concentrations of eight potentially toxic metals (PTMs) and four groups of organic pollutants in 15 sewage sludge and 12 river sediment samples, then linked measured contaminant concentrations to the toxicity of each matrix through constrained correspondence analysis (CCA). In sludge samples, Hg, As, hexachlorohexane (HCH), polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCD) influenced the toxicity profiles, with the first four having significant effects and HBCD being marginally significant...
September 23, 2016: Journal of Hazardous Materials
Louise von Stechow, Jesper V Olsen
Genomic instability is a critical driver in the process of cancer formation. At the same time, inducing DNA damage by irradiation or genotoxic compounds constitutes a key therapeutic strategy to kill fast-dividing cancer cells. Sensing of DNA lesions initiates a complex set of signalling pathways, collectively known as the DNA damage response (DDR). Deciphering DDR signalling pathways with high-throughput technologies could provide insights into oncogenic transformation, metastasis formation and therapy responses, and could build a basis for better therapeutic interventions in cancer treatment...
September 28, 2016: Proteomics
Zijun Wang, Heng Yin, Chak Sing Lau, Qianjin Lu
The complexity of immune system is tempered by precise regulation to maintain stabilization when exposed to various conditions. A subtle change in gene expression may be magnified when drastic changes are brought about in cellular development and function. Posttranslational modifications (PTMs) timely alter the functional activity of immune system, and work proceeded in these years has begun to throw light upon it. Posttranslational modifications of histone tails have been mentioned in a large scale of biological developments and disease progression, thereby making them a central field to investigate...
2016: International Journal of Molecular Sciences
Liqing Gu, Renã A S Robinson
Cysteine is a highly reactive amino acid and is subject to a variety of reversible post-translational modifications (PTMs), including nitrosylation, glutathionylation, palmitoylation, as well as formation of sulfenic acid and disulfides. These modifications are not only involved in normal biological activities, such as enzymatic catalysis, redox signaling and cellular homeostasis, but can also be the result of oxidative damage. Especially in aging and neurodegenerative diseases, oxidative stress leads to aberrant cysteine oxidations that affect protein structure and function leading to neurodegeneration as well as other detrimental effects...
September 26, 2016: Proteomics. Clinical Applications
Ahmed Arslan, Vera van Noort
MOTIVATION: The recent outbreak of Ebola virus disease (EVD) resulted in a large number of human deaths. Due to this devastation, the Ebola virus has attracted renewed interest as model for virus evolution. Recent literature on Ebola virus (EBOV) has contributed substantially to our understanding of the underlying genetics and its scope with reference to the 2014 outbreak. But no study yet, has focused on the conservation patterns of EBOV proteins. RESULTS: We analyzed the evolution of functional regions of EBOV and highlight the function of conserved residues in protein activities...
September 21, 2016: Bioinformatics
Xiangjun Li, Chaoyuan Li, Xiaoxia Li, Peihe Cui, Qifeng Li, Qiaoyan Guo, Hongbo Han, Shujun Liu, Guangdong Sun
Diabetic nephropathy (DN), a common complication associated with type 1 and type 2 diabetes mellitus (DM), characterized by glomerular mesangial expansion, inflammation, accumulation of extracellular matrix (ECM) protein, and hypertrophy, is the major cause of end-stage renal disease (ESRD). Increasing evidence suggested that p21-dependent glomerular and mesangial cell (MC) hypertrophy play key roles in the pathogenesis of DN. Recently, posttranscriptional modifications (PTMs) have uncovered novel molecular mechanisms involved in DN...
2016: Journal of Diabetes Research
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