The High Plasma Retinol Binding Protein 4 Level as a Risk Factor Consequently of Type 2 Diabetes Mellitus of Abdominal Obesity

Abdominal obesity (Ab-Ob) related to cardiometabolic risk, that is riskfactor constellation for succeeded cardiovasculer disease and type 2 DiabetesMellitus (DM). That factors such as atherogenic dislipidemia, hypertension,hyperglycemia, protrombotic state, and proinflammation state. Type 2 DMcharacterised by insulin resistance (IR). Plasma levels of retinol binding protein 4(RBP4) that is secreted by adipocytes are increased in insulin resistance (IR) state.Experiment in mice suggest that elevated RBP4 level cause IR. Although theunderlying mechanism is not clearly understood, RBP4 considered playimportance role consequently of type 2 DM in Ab-Ob.This research was carried out to determine the role of high plasma RBP4level as a risk factor consequently of type 2 DM in Ab-Ob. The research wasconducted by cross sectional analytic in 81 patients with Ab-Ob and case controlstudy with matching on 33 patients with Ab-Ob type 2 DM as cases and 33patients with Ab-Ob non type 2 DM as control. The plasma of TNF-?, sTNFR1,and RBP4 levels was measured by ELISA. IR status of the patients wasdetermined by HOMA-IR, whereas the ?-cell function was determined byHOMA-B. Ab-Ob was defined by using criteria for Asian peoples (male WC ? 90cm; female WC ? 80 cm). The result of 81 patients with Ab-Ob showed that bothplasma of TNF-? and sTNFR1 levels were significant positive correlated withplasma RBP4 level (coeficient correlation r = 0,294; p = 0,008 dan r = 0,458; p =<0,001 respectively). In addition, the plasma of RBP4 level significantly positivecorrelation with HOMA-IR (r = 0,450; p = 0,000) and significantly negativecorrelation with HOMA-B (r = -0,564; p = <0,001). In the matched case-controlstudy, it was shown that mean plasma of RBP4 level of type 2 DM group (76,08 ±16,84 ?g/ml) statistically higher than that without type 2 DM group (41,13 ±14,75 ?g/ml) (p = <0,001). The odds ratio higher plasma of RBP4 level was 5,426(CI 95%; 1,343 – 21, 928) statistically significant for increases risk type 2 DM (p= < 0,05). It has been proven that RBP4 was a dominant and consisten risk factor(66.9%, p = < 0.001) which influenced the incidence of type 2 DM in Ab-Ob. It can be concluded that high plasma of RBP4 level have a greater risk tosuffered from type 2 DM compared to low plasma of RBP4 in Ab-Ob. The highplasma of RBP4 level is most dominant and consistent risk factor consequently oftype 2 DM. These mechanism could behind the association between high plasmaof RBP4 level and type 2 DM

Jun Activation Domain-binding Protein 1 Antisense (P27Kip1) Induces Apoptosis of an Oral Tongue Cancer Cell

Jun activation domain-binding protein (Jab1) berperan sebagai koaktivator dari aktivator protein 1 yang terlibat dalam degradasi cyclin-dependent kinase inhibitor p27Kip1. Efek Jab1 antisense (Jab1-AS) diujikan pada sel kanker lidah manusia Supris-Clone 1 (Sp-C1). Tujuan penelitian ini adalah menganalisis hambatan sel SP-C1 dengan perlakuan Jab1-AS. Hasil penelitian menunjukkan bahwa Jab1-AS meningkatkan apoptosis yang ditandai dengan meningkatnya fase awal apoptosis (33,5%) dan fase lambat apoptosis (17,6%). Selain data tersebut, diketahui peningkatan aktivitas proteolitik caspase-3 dan caspase-9 pada sel yang diperlakukan dengan Jab1 AS. Kesimpulannya, Jab1 AS dapat meningkatkan apoptosis sel kanker lidah manusia (Sp-C1). Target pada molekul Jab1 dapat memberikan harapan baru sebagai pendekatan terapeutik untuk jenis kanker tersebut

Cyclosporin A-binding protein (cyclophilin) of Neurospora crassa

Cyclophilin (cyclosporin A-binding protein) has a dual localization in the mitochondria and in the cytosol of Neurospora crassa. The two forms are encoded by a single gene which is transcribed into mRNAs having different lengths and 5' termini (approximately 1 and 0.8 kilobases). The shorter mRNA specifies the cytosolic protein consisting of 179 amino acids. The longer mRNA is translated into a precursor polypeptide with an amino-terminal extension of 44 amino acids which is cleaved in two steps upon entry into the mitochondrial matrix. Neurospora cyclophilin shows about 60% sequence homology to human and bovine cyclophilins

Crystallization, data collection and data processing of maltose-binding protein (MalE) from the phytopathogen Xanthomonas axonopodis pv. citri

Maltose-binding protein is the periplasmic component of the ABC transporter responsible for the uptake of maltose/maltodextrins. The Xanthomonas axonopodis pv. citri maltose-binding protein MalE has been crystallized at 293 Kusing the hanging-drop vapour-diffusion method. The crystal belonged to the primitive hexagonal space group P6_122, with unit-cell parameters a = 123.59, b = 123.59, c = 304.20 Å, and contained two molecules in the asymetric unit. It diffracted to 2.24 Å resolution

An eIF4E-binding protein regulates katanin protein levels in C. elegans embryos.

In Caenorhabditis elegans, the MEI-1-katanin microtubule-severing complex is required for meiosis, but must be down-regulated during the transition to embryogenesis to prevent defects in mitosis. A cullin-dependent degradation pathway for MEI-1 protein has been well documented. In this paper, we report that translational repression may also play a role in MEI-1 down-regulation. Reduction of spn-2 function results in spindle orientation defects due to ectopic MEI-1 expression during embryonic mitosis. MEL-26, which is both required for MEI-1 degradation and is itself a target of the cullin degradation pathway, is present at normal levels in spn-2 mutant embryos, suggesting that the degradation pathway is functional. Cloning of spn-2 reveals that it encodes an eIF4E-binding protein that localizes to the cytoplasm and to ribonucleoprotein particles called P granules. SPN-2 binds to the RNA-binding protein OMA-1, which in turn binds to the mei-1 3 untranslated region. Thus, our results suggest that SPN-2 functions as an eIF4E-binding protein to negatively regulate translation of mei-1

An amphitropic cAMP-binding protein in yeast mitochondria

ABSTRACT: We describe the first example of a mitochondrial protein with a covalently attached phos-phatidylinositol moiety acting as a membrane anchor. The protein can be metabolically labeled with both stearic acid and inositol. The stearic acid label is removed by phospholipase D whereupon the protein with the retained inositol label is released from the membrane. This protein is a cAMP receptor of the yeast Saccharomyces cereuisiae and tightly associated with the inner mitochondrial membrane. However, it is converted into a soluble form during incubation of isolated mitochondria with Ca2+ and phospholipid (or lipid derivatives). This transition requires the action of a proteinaceous, N-ethylmaleimide-sensitive component of the intermembrane space and is accompanied by a decrease in the lipophilicity of the cAMP receptor. We propose that the component of the intermembrane space triggers the amphitropic behavior of the mitochondrial lipid-modified CAMP-binding protein through a phospholipase activity. Only in recent years specific fatty acids have been recog-nized to play important roles in the association of proteins with membranes. Both noncovalent and covalent interactions be-tween fatty acids and proteins have been reported. Among the latter are GTP-binding proteins (Molenaar et al., 1988)

From Nonspecific DNA–Protein Encounter Complexes to the Prediction of DNA–Protein Interactions

©2009 Gao, Skolnick. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.doi:10.1371/journal.pcbi.1000341DNA–protein interactions are involved in many essential biological activities. Because there is no simple mapping code between DNA base pairs and protein amino acids, the prediction of DNA–protein interactions is a challenging problem. Here, we present a novel computational approach for predicting DNA-binding protein residues and DNA–protein interaction modes without knowing its specific DNA target sequence. Given the structure of a DNA-binding protein, the method first generates an ensemble of complex structures obtained by rigid-body docking with a nonspecific canonical B-DNA. Representative models are subsequently selected through clustering and ranking by their DNA–protein interfacial energy. Analysis of these encounter complex models suggests that the recognition sites for specific DNA binding are usually favorable interaction sites for the nonspecific DNA probe and that nonspecific DNA–protein interaction modes exhibit some similarity to specific DNA–protein binding modes. Although the method requires as input the knowledge that the protein binds DNA, in benchmark tests, it achieves better performance in identifying DNA-binding sites than three previously established methods, which are based on sophisticated machine-learning techniques. We further apply our method to protein structures predicted through modeling and demonstrate that our method performs satisfactorily on protein models whose root-mean-square Ca deviation from native is up to 5 Å from their native structures. This study provides valuable structural insights into how a specific DNA-binding protein interacts with a nonspecific DNA sequence. The similarity between the specific DNA–protein interaction mode and nonspecific interaction modes may reflect an important sampling step in search of its specific DNA targets by a DNA-binding protein

RNA-binding protein CPEB1 remodels host and viral RNA landscapes.

Host and virus interactions occurring at the post-transcriptional level are critical for infection but remain poorly understood. Here, we performed comprehensive transcriptome-wide analyses revealing that human cytomegalovirus (HCMV) infection results in widespread alternative splicing (AS), shortening of 3' untranslated regions (3' UTRs) and lengthening of poly(A)-tails in host gene transcripts. We found that the host RNA-binding protein CPEB1 was highly induced after infection, and ectopic expression of CPEB1 in noninfected cells recapitulated infection-related post-transcriptional changes. CPEB1 was also required for poly(A)-tail lengthening of viral RNAs important for productive infection. Strikingly, depletion of CPEB1 reversed infection-related cytopathology and post-transcriptional changes, and decreased productive HCMV titers. Host RNA processing was also altered in herpes simplex virus-2 (HSV-2)-infected cells, thereby indicating that this phenomenon might be a common occurrence during herpesvirus infections. We anticipate that our work may serve as a starting point for therapeutic targeting of host RNA-binding proteins in herpesvirus infections

Glycolytic enzymes - novel carbohydrate binding proteins for glycoprotein analysis

•The cloning, expression, purification and characterisation of recombinant prokaryotic glycolytic enzymes •The mutagenesis of prokaryotic glycolytic enzymes to generate novel recombinant carbohydrate binding proteins •The characterisation of the binding profile of the novel recombinant carbohydrate binding protein

FUS mutant human motoneurons display altered transcriptome and microRNA pathways with implications for ALS pathogenesis

The FUS gene has been linked to amyotrophic lateral sclerosis (ALS). FUS is a ubiquitous RNA-binding protein, and the mechanisms leading to selective motoneuron loss downstream of ALS-linked mutations are largely unknown. We report the transcriptome analysis of human purified motoneurons, obtained from FUS wild-type or mutant isogenic induced pluripotent stem cells (iPSCs). Gene ontology analysis of differentially expressed genes identified significant enrichment of pathways previously associated to sporadic ALS and other neurological diseases. Several microRNAs (miRNAs) were also deregulated in FUS mutant motoneurons, including miR-375, involved in motoneuron survival. We report that relevant targets of miR-375, including the neural RNA-binding protein ELAVL4 and apoptotic factors, are aberrantly increased in FUS mutant motoneurons. Characterization of transcriptome changes in the cell type primarily affected by the disease contributes to the definition of the pathogenic mechanisms of FUS-linked ALS