Mol Biosyst [JOURNAL]
Sun
200 papers
Protein-protein interaction networks as a new perspective to evaluate distinct functional roles of voltage-dependent anion channel isoforms.
Caterino M, Ruoppolo M, Mandola A … +3 more , Costanzo M, Orrù S, Imperlini E
Mol Biosyst · 2017 Nov · PMID 29028058 · Publisher ↗
Voltage-dependent anion channels (VDACs) are a family of three mitochondrial porins and the most abundant integral membrane proteins of the mitochondrial outer membrane (MOM). VDACs are known to be involved in metabolite...
Voltage-dependent anion channels (VDACs) are a family of three mitochondrial porins and the most abundant integral membrane proteins of the mitochondrial outer membrane (MOM). VDACs are known to be involved in metabolite/ion transport across the MOM and in many cellular processes ranging from mitochondria-mediated apoptosis to the control of energy metabolism, by interacting with cytosolic, mitochondrial and cytoskeletal proteins and other membrane channels. Despite redundancy and compensatory mechanisms among VDAC isoforms, they display not only different channel properties and protein expression levels, but also distinct protein partners. Here, we review the known protein interactions for each VDAC isoform in order to shed light on their peculiar roles in physiological and pathological conditions. As proteins associated with the MOM, VDAC opening/closure as a metabolic checkpoint is regulated by protein-protein interactions, and is of pharmacological interest in pathological conditions such as cancer. The interactions involving VDAC1 have been characterized more in depth than those involving VDAC2 and VDAC3. Nevertheless, the so far explored VDAC-protein interactions for each isoform show that VDAC1 is mainly involved in the maintenance of cellular homeostasis and in pro-apoptotic processes, whereas VDAC2 displays an anti-apoptotic role. Despite there being limited information on VDAC3, this isoform could contribute to mitochondrial protein quality control and act as a marker of oxidative status. In pathological conditions, namely neurodegenerative and cardiovascular diseases, both VDAC1 and VDAC2 establish abnormal interactions aimed to counteract the mitochondrial dysfunction which contributes to end-organ damage.
Prediction of drug-pathway interaction pairs with a disease-combined LSA-PU-KNN method.
Chen FS, Jiang HY, Jiang Z
Mol Biosyst · 2017 Nov · PMID 29022624 · Publisher ↗
Prediction of new associations between drugs and targeting pathways can provide valuable clues for drug discovery & development. However, information integration and a class-imbalance problem are important challenges for...
Prediction of new associations between drugs and targeting pathways can provide valuable clues for drug discovery & development. However, information integration and a class-imbalance problem are important challenges for available prediction methods. This paper proposes a prediction of potential associations between drugs and pathways based on a disease-related LSA-PU-KNN method. Firstly, we built a drug-disease-pathway network and combined the drug-disease and pathway-disease features obtained by different types of feature profiles. Then we applied a latent semantic analysis (LSA) method to perform dimension reduction by combining positive-unlabeled (PU) learning and k nearest neighbors (KNN) method. The experimental results showed that our method can achieve a higher AUC (the area under the ROC curve) and AUPR (the area under the PR curve) than other typical methods. Furthermore, some interesting drug-pathway interaction pairs were identified and validated.
MicroRNA-590-5p regulates cell viability, apoptosis, migration and invasion of renal cell carcinoma cell lines through targeting ARHGAP24.
Wang L, Wei WQ, Wu ZY … +1 more , Wang GC
Mol Biosyst · 2017 Nov · PMID 29019371 · Publisher ↗
Renal cell carcinoma (RCC) is the leading cause of death in renal malignancies. MicroRNA-590-5p (miR-590-5p) is of great importance in the processes of many cancers regarding regulation of cancer cell invasion and prolif...
Renal cell carcinoma (RCC) is the leading cause of death in renal malignancies. MicroRNA-590-5p (miR-590-5p) is of great importance in the processes of many cancers regarding regulation of cancer cell invasion and proliferation. In our study, alternation of miR-590-5p expression in RCC cell lines through transfection with pre-miR-590-5p (up-regulation) or anti-miR-590-5p (down-regulation) was performed. Apoptosis and viability of RCC cell lines were measured by flow cytometry and CCK-8 analysis, respectively. Cell invasion and migration were estimated by Transwell assay. The association of miR-590-5p with ARHGAP24 expression was evaluated using luciferase assays, real-time PCR and western blot assay. The expressions of apoptosis and migration-related protein were also measured by western blotting. We found that pre-miR-590-5p transfection in Caki-2 and 786-O cells showed significant increases in cell viability, invasion and migration, which were accompanied by decreased cell apoptosis, while anti-miR-590-5p transfection obviously inhibited the cell viability, migration and invasion of Caki-2 and 786-O cells as well as induced apoptosis, compared with the negative control group. Furthermore, bioinformatics combined with luciferase reporter assays indicated that ARHGAP24 is directly targeted by miR-590-5p. ARHGAP24 overexpression in 786-O and Caki-2 cells phenocopied the effects of anti-miR-590-5p transfection along with enhanced expression of active Caspase-3 and Bax/Bcl-2 ratio as well as decreased expression of MMP-2 and MMP-9. These findings suggested that miR-590-5p/ARHGAP24 seems to function as a potentially beneficial target for RCC treatment.
Evaluation and optimization of reduction and alkylation methods to maximize peptide identification with MS-based proteomics.
Suttapitugsakul S, Xiao H, Smeekens J … +1 more , Wu R
Mol Biosyst · 2017 Nov · PMID 29019370 · Full text
Mass spectrometry (MS) has become an increasingly important technique to analyze proteins. In popular bottom-up MS-based proteomics, reduction and alkylation are routine steps to facilitate peptide identification. Howeve...
Mass spectrometry (MS) has become an increasingly important technique to analyze proteins. In popular bottom-up MS-based proteomics, reduction and alkylation are routine steps to facilitate peptide identification. However, incomplete reactions and side reactions may occur, which compromise the experimental results. In this work, we systematically evaluated the reduction step with commonly used reagents, i.e., dithiothreitol, 2-mercaptoethanol, tris(2-carboxyethyl)phosphine, or tris(3-hydroxypropyl)phosphine, and alkylation with iodoacetamide, acrylamide, N-ethylmaleimide, or 4-vinylpyridine. By using digested peptides from a yeast whole-cell lysate, the number of proteins and peptides identified were very similar using four different reducing reagents. The results from four alkylating reagents, however, were dramatically different with iodoacetamide giving the highest number of peptides with alkylated cysteine and the lowest number of peptides with incomplete cysteine alkylation and side reactions. Alkylation conditions with iodoacetamide were further optimized. To identify more peptides with cysteine, thiopropyl-sepharose 6B resins were used to enrich them, and the optimal conditions were employed for the reduction and alkylation. The enrichment resulted in over three times more cysteine-containing peptides than without enrichment. Systematic evaluation of the reduction and alkylation with different reagents can aid in a better design of bottom-up proteomic experiments.
Role of solvent properties of water in crowding effects induced by macromolecular agents and osmolytes.
Ferreira LA, Uversky VN, Zaslavsky BY
Mol Biosyst · 2017 Nov · PMID 29018861 · Publisher ↗
Solvent properties of water in aqueous solutions of polyethylene glycols of various molecular weights, l-proline, betaine, and a series of chlorides of varied concentrations are assayed using three solvatochromic dyes. T...
Solvent properties of water in aqueous solutions of polyethylene glycols of various molecular weights, l-proline, betaine, and a series of chlorides of varied concentrations are assayed using three solvatochromic dyes. The properties include solvent dipolarity/polarizability, hydrogen bond donor acidity, and hydrogen bond acceptor basicity. These properties are also evaluated in mixtures of two polymers, polymer and osmolyte, and two osmolytes. It is shown that linear combinations of solvent dipolarity/polarizability and hydrogen bond donor acidity assayed in individual solutions of crowders strongly correlate with the effects of the crowders on the stability of various proteins and nucleic acids reported in the literature. The solvent properties of water in aqueous mixtures of two macromolecular crowders, two osmolytes, or mixtures of an osmolyte and a macromolecular crowder vary differently for various solvent properties. The overall effects of the two components in the mixture on a given solvent property of water may be additive, reduced or enhanced depending on the particular composition of the mixture. It is hypothesized that changes in the solvent properties of water are related to changes in the water hydrogen-bonding structuring. It is suggested that the observed crowder-induced changes in the solvent properties of water should be taken into account in theoretical considerations of crowding effects in biological systems.
Computational identification of protein S-sulfenylation sites by incorporating the multiple sequence features information.
Hasan MM, Guo D, Kurata H
Mol Biosyst · 2017 Nov · PMID 28990628 · Publisher ↗
Cysteine S-sulfenylation is a major type of posttranslational modification that contributes to protein structure and function regulation in many cellular processes. Experimental identification of S-sulfenylation sites is...
Cysteine S-sulfenylation is a major type of posttranslational modification that contributes to protein structure and function regulation in many cellular processes. Experimental identification of S-sulfenylation sites is challenging, due to the low abundance of proteins and the inefficient experimental methods. Computational identification of S-sulfenylation sites is an alternative strategy to annotate the S-sulfenylated proteome. In this study, a novel computational predictor SulCysSite was developed for accurate prediction of S-sulfenylation sites based on multiple sequence features, including amino acid index properties, binary amino acid codes, position specific scoring matrix, and compositions of profile-based amino acids. To learn the prediction model of SulCysSite, a random forest classifier was applied. The final SulCysSite achieved an AUC value of 0.819 in a 10-fold cross-validation test. It also exhibited higher performance than other existing computational predictors. In addition, the hidden and complex mechanisms were extracted from the predictive model of SulCysSite to investigate the understandable rules (i.e. feature combination) of S-sulfenylation sites. The SulCysSite is a useful computational resource for prediction of S-sulfenylation sites. The online interface and datasets are publicly available at .
Gene co-opening network deciphers gene functional relationships.
Li W, Wang M, Sun J … +2 more , Wang Y, Jiang R
Mol Biosyst · 2017 Oct · PMID 28976510 · Publisher ↗
Genome sequencing technology has generated a vast amount of genomic and epigenomic data, and has provided us a great opportunity to study gene functions on a global scale from an epigenomic view. In the last decade, netw...
Genome sequencing technology has generated a vast amount of genomic and epigenomic data, and has provided us a great opportunity to study gene functions on a global scale from an epigenomic view. In the last decade, network-based studies, such as those based on PPI networks and co-expression networks, have shown good performance in capturing functional relationships between genes. However, the functions of a gene and the mechanism of interaction of genes with each other to elucidate their functions are still not entirely clear. Here, we construct a gene co-opening network based on chromatin accessibility of genes. We show that genes related to a specific biological process or the same disease tend to be clustered in the co-opening network. This understanding allows us to detect functional clusters from the network and to predict new functions for genes. We further apply the network to prioritize disease genes for Psoriasis, and demonstrate the power of the joint analysis of the co-opening network and GWAS data in identifying disease genes. Taken together, the co-opening network provides a new viewpoint for the elucidation of gene associations and the interpretation of disease mechanisms.
PANDAR: a pivotal cancer-related long non-coding RNA in human cancers.
Li J, Li Z, Zheng W … +4 more , Li X, Wang Z, Cui Y, Jiang X
Mol Biosyst · 2017 Oct · PMID 28976505 · Publisher ↗
Long non-coding RNAs (lncRNAs), non-protein-coding RNAs that are more than 200 nucleotides in length, have been demonstrated to play a vital role in the pathophysiology of human diseases, particularly in tumorigenesis an...
Long non-coding RNAs (lncRNAs), non-protein-coding RNAs that are more than 200 nucleotides in length, have been demonstrated to play a vital role in the pathophysiology of human diseases, particularly in tumorigenesis and progression of cancers. Dysregulation of lncRNAs, which serve as either oncogenes or tumor suppressor genes, is involved in diverse cellular processes, such as proliferation, dedifferentiation, migration, invasion and anti-apoptosis. Promoter of CDKN1A antisense DNA damage-activated RNA (PANDAR), which was recently found to manifest aberrant expression in various malignancies including non-small cell lung cancer, hepatocellular carcinoma, colorectal cancer and gastric cancer, is a novel cancer-related lncRNA. Deregulation of PANDAR contributes to tumorigenesis and progression of cancers, suggesting that PANDAR is likely to represent a viable biomarker and therapeutic target for human cancers. In this review, we summarize current evidence regarding the biological functions and mechanisms of PANDAR during tumor development.
The Henipavirus V protein is a prevalently unfolded protein with a zinc-finger domain involved in binding to DDB1.
Salladini E, Delauzun V, Longhi S
Mol Biosyst · 2017 Oct · PMID 28972216 · Publisher ↗
Henipaviruses are severe human pathogens within the Paramyxoviridae family. Beyond the P protein, the Henipavirus P gene also encodes the V protein which shares with P its N-terminal, intrinsically disordered region (PNT...
Henipaviruses are severe human pathogens within the Paramyxoviridae family. Beyond the P protein, the Henipavirus P gene also encodes the V protein which shares with P its N-terminal, intrinsically disordered region (PNT) and possesses a unique C-terminal domain predicted to be folded and to bind zinc (ZnFD). Henipavirus V proteins antagonize IFN signaling through PNT-mediated binding to STAT1, and several paramyxoviral V proteins promote STAT1 degradation through binding to DDB1. Structural and molecular information on Henipavirus V proteins is lacking, and their ability to interact with DDB1 has not been documented yet. We cloned the V genes from Nipah and Hendra viruses and purified the V proteins from E. coli and DDB1 from insect cells. Using analytical size-exclusion chromatography, CD and SAXS we characterized the V proteins and their domains. Using pull-down and MST we assessed their binding abilities towards DDB1. We show that PNT remains disordered also in the context of the V protein, while the ZnFD adopts a predominant β conformation. We also show that the V proteins interact with DDB1 predominantly via their ZnFD. This is the first experimental characterization of the Henipavirus V proteins and the first experimental evidence of their interaction with DDB1. The DDB1-ZnFD interaction constitutes a promising target for antiviral strategies. These studies provide a conceptual asset to design new antiviral strategies expected to reduce or abrogate the ability of these viruses to escape the innate immune response. They also contribute to illuminating the conformational behaviour of proteins encompassing large intrinsically disordered domains.
A computational method using differential gene expression to predict altered metabolism of multicellular organisms.
Zhu L, Zheng H, Hu X … +1 more , Xu Y
Mol Biosyst · 2017 Oct · PMID 28972214 · Publisher ↗
Altered metabolism is often identified as a cause or an effect of physiology and pathogenesis. But it is difficult to predict the metabolic flux distributions of multicellular organisms due to the lack of an explicit met...
Altered metabolism is often identified as a cause or an effect of physiology and pathogenesis. But it is difficult to predict the metabolic flux distributions of multicellular organisms due to the lack of an explicit metabolic objective function. Here we present a computational method which can successfully describe the differences in metabolism between two different conditions on a large scale. By integrating gene expression data with an existing comprehensive reconstruction of the global human metabolic network, we qualitatively predicted significantly differential fluxes without prior knowledge or the rate of metabolite uptake and secretion. Therefore, this method can be applied for both microorganisms and multicellular organisms. Different from traditional enrichment analysis methods and constraint-based models, we consider conditions and interactions within the metabolic network simultaneously. To apply the proposed method, we predicted altered fluxes for E. coli strains and clear cell renal cell carcinoma, while the E. coli strains are growing aerobically in a chemostat with different dilution rates and clear cell renal cell carcinoma is compared with normal kidney cells. Then we map the significantly differential reactions to metabolic subsystems defined in the original metabolic network for ccRCC to observe the altered metabolism. In contrast with existing studies, our results show a high accuracy of the E. coli experiment and a more reasonable prediction of the ccRCC experiment. The method presented here provides a computational approach for the genome-wide study of altered metabolism under pairs of conditions for both microorganisms and multicellular organisms.
Dynamic properties of dipeptidyl peptidase III from Bacteroides thetaiotaomicron and the structural basis for its substrate specificity - a computational study.
Tomin M, Tomić S
Mol Biosyst · 2017 Oct · PMID 28971197 · Publisher ↗
Dipeptidyl peptidase III (DPP III) from the human gut symbiont Bacteroides thetaiotaomicron (Bt) is the first identified prokaryotic DPP III orthologue. It has low sequence similarity to the thoroughly studied human DPP...
Dipeptidyl peptidase III (DPP III) from the human gut symbiont Bacteroides thetaiotaomicron (Bt) is the first identified prokaryotic DPP III orthologue. It has low sequence similarity to the thoroughly studied human DPP III, and differently from eukaryotic orthologues it has a cysteine (Cys450) residue in the zinc-binding motif HEXXGH (HECLGH). The recently determined crystal structure of BtDPP III showed that its 3D structure, similar to the structure of the human DPP III, consists of two domains with a wide cleft in between. Although such a striking similarity of the 3D structures of orthologues with low sequence similarity is not surprising, it is no guarantee for similarity of their dynamic properties and the catalytic performance. Here, we report the results of the molecular modelling study of BtDPP III, wild type and its C450S mutant, as well as their complexes with characteristic DPP III substrates Arg-Arg-2-naphthylamide (RRNA) and Lys-Ala-2-naphtylamide (KANA). During several hundred nanoseconds of all-atom MD simulations of the wild type protein, the long range conformational changes, which can be described as protein 'closing', have been traced. We have determined a similar conformational change for the human orthologue as well. However, the amplitude of the change is lower for BtDPP III than for the human DPP III. The MD simulations have been performed using ff03, ff12SB and ff14SB force fields wherein the results of the last two better fit to the experimental results. The hydrogen bond analysis indicates reasons for higher substrate specificity of BtDPP III towards RRNA than KANA as well as for the decrease of the RRNA hydrolysis rate induced by the Cys450 to Ser mutation. The obtained results are in line with the experimental data.
Screening for concanavalin A binders from a mannose-modified α-helix peptide phage library.
Ven Chang I, Tsutsumi H, Mihara H
Mol Biosyst · 2017 Oct · PMID 28967020 · Publisher ↗
Mannose-modified lectin-binding peptides were obtained from an α-helical-designed peptide phage library. Concanavalin A (ConA) was used as a representative target protein for the lectin family. The identified glycopeptid...
Mannose-modified lectin-binding peptides were obtained from an α-helical-designed peptide phage library. Concanavalin A (ConA) was used as a representative target protein for the lectin family. The identified glycopeptides could selectively bind to ConA with micromolar affinity. With these results, the methodologies described in this study will enhance the selection of saccharide-modified ligands through the synergistic effects of sugar and peptide units, with better specificity and affinity towards lectin proteins.
Lipidomic alterations of in vitro macrophage infection by L. infantum and L. amazonensis.
Negrão F, Abánades DR, Jaeeger CF … +5 more , Rocha DFO, Belaz KRA, Giorgio S, Eberlin MN, Angolini CFF
Mol Biosyst · 2017 Oct · PMID 28960008 · Publisher ↗
Particular lipid profiles have been found in two different protozoa of the Leishmania genus. Leishmania infantum, a visceral leishmaniasis causative agent and Leishmania amazonensis, a cutaneous leishmaniasis, reveal dis...
Particular lipid profiles have been found in two different protozoa of the Leishmania genus. Leishmania infantum, a visceral leishmaniasis causative agent and Leishmania amazonensis, a cutaneous leishmaniasis, reveal distinctive lipid contents of phosphatidylethanolamine and phosphatidylserine plasmalogens, sphingolipids, phosphatidylinositols, phosphatidylcholine, and phosphatidylethanolamine, which have been shown to be related to species, life-cycle of the parasite, and macrophage infection. L. infantum displayed a higher content of phosphatidylethanolamine plasmalogens than L. amazonensis, which may help to differentiate their unique clinical manifestations. Phosphatidylserines plasmalogens are also found to be an important lipid class for the intracellular form of the parasite. Our findings also reveal lipid classes that may be involved in visceralization pathways and parasite differentiation.
Metabolomics reveal mitochondrial and fatty acid metabolism disorders that contribute to the development of DKD in T2DM patients.
Li L, Wang C, Yang H … +4 more , Liu S, Lu Y, Fu P, Liu J
Mol Biosyst · 2017 Oct · PMID 28956034 · Publisher ↗
Diabetic kidney disease (DKD) is the leading cause of ESRD; however, early intervention can greatly prevent the progression of DKD; thus, sensitive biomarkers for DKD are still required. This study was aimed at the ident...
Diabetic kidney disease (DKD) is the leading cause of ESRD; however, early intervention can greatly prevent the progression of DKD; thus, sensitive biomarkers for DKD are still required. This study was aimed at the identification of potential biomarkers and revelation of underlying pathways in DKD patients by non-targeted metabolomics. Gas chromatography-mass spectrometry was used to analyze urine obtained from the control and type 2 diabetes mellitus (T2DM) and DKD patients, and the renal histological changes in DKD patients were assessed. The DKD group showed increased level of uric acid, 1,5-anhydroglucitol, hippuric acid, stearic acid, and palmitic acid and reduced level of uracil, glycine, aconitic acid, isocitric acid, 4-hydroxybutyrate, 2-deoxyerythritol, and glycolic acid as compared to the control and T2DM groups. Further analysis indicated that many of the changed metabolites were involved in mitochondrial and fatty acid (FA) metabolism, and combined mitochondrial and FA metabolites showed better diagnosis values for DKD. Histological results confirmed that renal expression of key proteins was reduced in DKD patients with respect to mitochondrial biogenesis (PGC-1α, p-AMPK) and FA oxidation (PPAR-α, CPT-1) as compared to that in the control and T2DM groups. This study highlighted that both mitochondrial and FA metabolism were disturbed in DKD, and thus, they could serve as combined biomarkers for the prediction of DKD.
Modelling the propagation of a dynamical signature in gene expression mediated by the transport of extracellular microRNAs.
Grau Ribes A, De Decker Y, Gérard C … +1 more , Rongy L
Mol Biosyst · 2017 Oct · PMID 28953276 · Publisher ↗
Extracellular microRNAs (miRNAs) carried by exosomes can play a key role in cell-to-cell communication. Deregulation of miRNA expression and exosome secretion have been related to pathological conditions such as cancer....
Extracellular microRNAs (miRNAs) carried by exosomes can play a key role in cell-to-cell communication. Deregulation of miRNA expression and exosome secretion have been related to pathological conditions such as cancer. While it is known that circulating miRNAs can alter gene expression in recipient cells, it remains unclear how significant the dynamical impact of these extracellular miRNAs is. To shed light on this issue, we propose a model for the spatio-temporal evolution of the protein expression in a cell tissue altered by abnormal miRNA expression in a donor cell. This results in a nonhomogeneous cellular response in the tissue, which we quantify by studying the range of action of the donor cell on the surrounding cells. Key model parameters that control the range of action are identified. Based on a model for a heterogeneous cell population, we show that the dynamics of gene expression in the tissue is robust to random changes of the parameter values. Furthermore, we study the propagation of gene expression oscillations in a tissue induced by extracellular miRNAs. In the donor cell, the miRNA inhibits its own transcription which can give rise to local oscillations in gene expression. The resulting oscillations of the concentration of extracellular miRNA induce oscillations of the protein concentration in recipient cells. We analyse the nonmonotonic spatial evolution of the oscillation amplitude of the protein concentration in the tissue which may have implications for the propagation of oscillations in biological rhythms such as the circadian clock.
Identification of a suitable promoter for the sigma factor of Mycobacterium tuberculosis.
Mallick Gupta A, Mukherjee S, Dutta A … +3 more , Mukhopadhyay J, Bhattacharyya D, Mandal S
Mol Biosyst · 2017 Oct · PMID 28952652 · Publisher ↗
Promoter binding specificity is one of the important characteristics of transcription by Mycobacterium tuberculosis (Mtb) sigma (σ) factors, which remains unexplored due to limited structural evidence. Our previous study...
Promoter binding specificity is one of the important characteristics of transcription by Mycobacterium tuberculosis (Mtb) sigma (σ) factors, which remains unexplored due to limited structural evidence. Our previous study on the structural features of Mtb-SigH, consisting of three alpha helices, and its interaction with core RNA polymerase has been extended herein to determine the little known DNA sequence recognition pattern involving its cognate promoters. Herein, high resolution X-ray crystallographic structures of the protein-DNA complexes were inspected to determine the tentative DNA-binding helix of the σ factor. The binding interface in the available crystal structures is found to be populated mainly with specific residues such as Arg, Asn, Lys, Gln, and Ser. We uncovered the helix 3 of Mtb-SigH containing most of these amino acids, which ranged from Arg 64 to Arg 75, forming the predicted active site. The complex of Mtb-SigH:DNA is modelled with 20 promoter sequences. The binding affinity is predicted by scoring these protein-DNA complexes through proximity and interaction parameters obtained by molecular dynamics simulations. The promoters are ranked considering hydrogen bonding, energy of interaction, buried surface area, and distance between centers of masses in interaction with the protein. The ranking is validated through in vitro transcription assays. The trends of these selected promoter interactions have shown variations parallel to the experimental evaluation, emphasizing the success of the active site determination along with screening of the promoter strength. The promoter interaction of Mtb-SigH can be highly beneficial for understanding the regulation of gene expression of a pathogen and also extends a solid platform to predict promoters for other bacterial σ factors.
CarSite: identifying carbonylated sites of human proteins based on a one-sided selection resampling method.
Zuo Y, Jia CZ
Mol Biosyst · 2017 Oct · PMID 28937156 · Publisher ↗
Protein carbonylation is one of the most important biomarkers of oxidative protein damage and such protein damage is linked to various diseases and aging. It is thus vital that carbonylation sites are identified accurate...
Protein carbonylation is one of the most important biomarkers of oxidative protein damage and such protein damage is linked to various diseases and aging. It is thus vital that carbonylation sites are identified accurately. In this study, CarSite, a novel bioinformatics tool, was established to identify carbonylation sites in human proteins. The one-sided selection (OSS) resampling method was used to establish balanced training datasets and this resampling method is demonstrated to perform better than a Monte Carlo resampling method via 10-fold cross-validation tests on the Jia dataset. Moreover, the hybrid combination of position-specific amino acid propensity (PSAAP), composition of k-spaced amino acid pairs (CKSAAP), amino acid composition (AAC), and composition of hydrophobic and hydrophilic amino acids (CHHAA) was selected to optimize the performance of the predictor. On 10-fold cross-validation of the Jia dataset, CarSite obtained rates of sensitivity corresponding to K/P/R/T-type peptides of ∼21%, 22%, 19%, or 18% higher than those obtained by iCar-PseCp, respectively, which was previously considered as the best predictor for identifying carbonylation sites in human proteins. Furthermore, compared with other existing predictors, CarSite obtained much higher sensitivity and accuracy when tested on the same dataset.
Long non-coding RNA SNHG17 is an unfavourable prognostic factor and promotes cell proliferation by epigenetically silencing P57 in colorectal cancer.
Ma Z, Gu S, Song M … +7 more , Yan C, Hui B, Ji H, Wang J, Zhang J, Wang K, Zhao Q
Mol Biosyst · 2017 Oct · PMID 28933484 · Publisher ↗
Recently, substantial evidence has demonstrated that long non-coding RNAs (lncRNAs) play critical roles in multiple cancers including colorectal cancer (CRC). Utilizing publicly available lncRNA-expression-profiling data...
Recently, substantial evidence has demonstrated that long non-coding RNAs (lncRNAs) play critical roles in multiple cancers including colorectal cancer (CRC). Utilizing publicly available lncRNA-expression-profiling data from the Gene Expression Omnibus (GEO) dataset GSE21510, we screened SNHG17 as a new candidate lncRNA associated with CRC development and progression. We further demonstrated that SNHG17 was upregulated in CRC tissues, and that its overexpression was significantly correlated with tumor size, TNM stage, and lymph node metastasis in CRC patients. Moreover, SNHG17 knockdown significantly inhibited the proliferation of CRC cells, and induced cell cycle G1/G0 phase arrest and cell apoptosis. Consistent with these findings, SNHG17 silencing inhibited tumor growth in vivo. Mechanistic studies revealed the capability of lncRNA SNHG17 to epigenetically suppress P57 by binding to enhancer of zeste homolog 2 (a key component of polycomb repressive complex 2) in CRC cells, and quantitative real-time polymerase chain reaction assays demonstrated that SNHG17 expression levels were inversely correlated with those of P57 in CRC tissues. Furthermore, rescue experiments confirmed that SNHG17 exerted oncogenic functions partly through regulating P57 expression. These findings represent the first reporting of the roles and mechanisms associated with SNHG17 in CRC progression, highlighting SNHG17 as a potential therapeutic target for CRC patients.
Imperfect crowding adaptation of mammalian cells towards osmotic stress and its modulation by osmolytes.
Gnutt D, Brylski O, Edengeiser E … +2 more , Havenith M, Ebbinghaus S
Mol Biosyst · 2017 Oct · PMID 28929156 · Publisher ↗
Changes of the extracellular milieu could affect cellular crowding. To prevent detrimental effects, cells use adaptation mechanisms to react to such conditions. Using fluorescent crowding sensors, we show that the initia...
Changes of the extracellular milieu could affect cellular crowding. To prevent detrimental effects, cells use adaptation mechanisms to react to such conditions. Using fluorescent crowding sensors, we show that the initial response to osmotic stress is fast but imperfect, while the slow response renders cells more tolerant to stress, particularly in the presence of osmolytes.
Methylglyoxal attenuates insulin signaling and downregulates the enzymes involved in cholesterol biosynthesis.
Deshmukh AB, Bai S, T A … +7 more , Kazi RS, Banarjee R, Rathore R, Mv V, Hv T, Kumar Bhat M, Mj K
Mol Biosyst · 2017 Oct · PMID 28926063 · Publisher ↗
Methylglyoxal (MG) is a highly reactive dicarbonyl known to be elevated under the hyperglycemic conditions of diabetes and is implicated in the development of diabetic complications. Therefore, the current study investig...
Methylglyoxal (MG) is a highly reactive dicarbonyl known to be elevated under the hyperglycemic conditions of diabetes and is implicated in the development of diabetic complications. Therefore, the current study investigates the role of MG in exacerbating insulin resistance at the insulin signaling level, as well as its effect on the global proteomic level. By using insulin sensitive rat muscle cells (L6) and Chinese hamster ovary (CHO) cells stably expressing the insulin receptor (IR) and a glucose transporter fused with green fluorescent protein (GLUT4-GFP), we have observed that MG impairs insulin signaling, inhibits GLUT4 translocation and reduces glucose uptake. SWATH MS analysis, a label-free quantitative mass spectrometric approach, showed altered expression of 99 proteins out of 2404 identified in response to MG treatment. These proteins are mainly involved in stress response, protein folding and proteolysis. Some of the deregulated proteins such as thioredoxin 2, glutathione S transferase, T complex protein 1 subunit β (tcbp1), heat shock protein 90 and E3 ubiquitin ligase were previously reported to be associated with either diabetes or insulin resistance. Interestingly, aminoguanidine (AMG), a potent dicarbonyl scavenger, restored the deleterious effects of MG. For the first time, we report that MG induces downregulation of enzymes involved in cholesterol biosynthesis such as acetyl-CoA acetyltransferase, hydroxymethylglutaryl-CoA synthase, farnesyl pyrophosphate synthetase, squalene monooxygenase, and lanosterol synthase. GC MS analysis for sterol metabolites corroborated the proteomic results; MG significantly reduced cholesterol production whereas AMG treatment restored cholesterol production to levels similar to the control. Thus, MG leads to primary defects in insulin signaling and cellular abnormalities at the proteomic and metabolic levels, both of which may contribute to the development of insulin resistance.
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