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Erratum to: Potentiation of TRAIL killing activity by multimerization through isoleucine zipper hexamerization motif.
Abstract The BMB Reports would like to correct in the ACKNOWLEDGEMENTS of BMB Rep. 49(5), 282-287 titled "Potentiation of TRAIL killing activity by multimerization through isoleucine zipper hexamerization motif." PMID: 29279065 [PubMed - in process] (Source: BMB Reports)
Source: BMB Reports - December 1, 2017 Category: Biochemistry Authors: Han JH, Moon AR, Chang JH, Bae J, Choi JM, Lee SH, Kim TH Tags: BMB Rep Source Type: research

Promoting and Improving Three Rs Practice: The Korean Guidelines.
Abstract Scientists planning research that involves the use of animals are required to examine the possibilities for replacement, reduction, or refinement (the Three Rs), and their protocol must be reviewed by the Institutional Animal Care and Use Committee. Good scientific practice involving appropriate search techniques on the available Three Rs resources is essential for both ethical and scientific reasons. Appropriate experimental design and statistical analysis techniques are particularly necessary for research involving the use of animals, because this can improve animal welfare and scientific outcomes, as w...
Source: BMB Reports - November 29, 2017 Category: Biochemistry Authors: Choe BI, Lee GH Tags: BMB Rep Source Type: research

Prevalence of negative frequency-dependent selection, revealed by incomplete selective sweeps in African populations of Drosophila melanogaster.
In conclusion, genomic patterns of positive selection are very diverse, with equal contributions of hard and soft sweeps and a surprisingly large proportion of frequency-dependent selection in D. melanogaster populations. PMID: 29187282 [PubMed - as supplied by publisher] (Source: BMB Reports)
Source: BMB Reports - November 29, 2017 Category: Biochemistry Authors: Kim Y Tags: BMB Rep Source Type: research

New Insights into Transglutaminase 2 and Links to Neurodegenerative Diseases.
Abstract Formation of toxic protein aggregates is a common feature and mainly contributes to the pathogenesis of neurodegenerative diseases (NDDs), which include amyotrophic lateral sclerosis (ALS), Alzheimer's, Parkinson's, Huntington's, and prion diseases. The transglutaminase 2 (TG2) gene encodes a multifunctional enzyme, displaying four types of activity, such as transamidation, GTPase, protein disulfide isomerase, and protein kinase activities. Many studies demonstrated that the calcium-dependent transamidation activity of TG2 affected the formation of insoluble and toxic amyloid aggregates that mainly consis...
Source: BMB Reports - November 29, 2017 Category: Biochemistry Authors: Min B, Chung KC Tags: BMB Rep Source Type: research

JQ1, a BET inhibitor, controls TLR4-induced IL-10 production in regulatory B cells by BRD4-NF- κB axis.
In this study, JQ1 potently suppressed IL-10 expression and secretion in murine splenic and peritoneal B cells. While bromodomain-containing protein 4 (BRD4) was associated with NF-κB on IL-10 promoter region by LPS stimulation, JQ1 interfered the interaction of BRD4 with NF-κB on IL-10 promoter. In summary, BRD4 is essential for toll like receptor 4 (TLR4)-mediated IL-10 expression, suggesting JQ1 could be a potential candidate in regulating IL-10-producing regulatory B cells in cancer. PMID: 29187284 [PubMed - as supplied by publisher] (Source: BMB Reports)
Source: BMB Reports - November 29, 2017 Category: Biochemistry Authors: Lee MB, Lee J, Hong SH, You JS, Nam ST, Kim HW, Park YH, Lee D, Min KY, Park YM, Kim YM, Kim HS, Choi WS Tags: BMB Rep Source Type: research

HCBP6 upregulates human SREBP1c expression by binding to C/EBP β-binding site in the SREBP1c promoter.
HCBP6 upregulates human SREBP1c expression by binding to C/EBPβ-binding site in the SREBP1c promoter. BMB Rep. 2017 Nov 20;: Authors: Yang X, Han M, Liu S, Yuan X, Liu X, Feng S, Zhou L, Li Y, Lu H, Cheng J, Lin S Abstract Sterol regulatory element-binding protein-1c (SREBP1c) plays an important role in triglyceride (TG) homeostasis. Although our previous study showed that hepatitis C virus core-binding protein 6 (HCBP6) regulates SREBP1c expression to maintain intracellular TG homeostasis, the mechanism underlying this regulation is unclear. In the present study, we found that HCBP6 increased in...
Source: BMB Reports - November 20, 2017 Category: Biochemistry Authors: Yang X, Han M, Liu S, Yuan X, Liu X, Feng S, Zhou L, Li Y, Lu H, Cheng J, Lin S Tags: BMB Rep Source Type: research

Upstream Signalling of mTORC1 and Its Hyperactivation in Type 2 Diabetes (T2D).
In conclusion, we suggest the regulatory roles of telomerase (TERT) and hexokinase II (HKII) on mTORC1 as possible remedies to treat hyperactivation. The former inhibits mTORC1 under nutrient-rich while the latter under starved condition. We provide an idea of TOS (TOR signaling) motifs that can be used for regulation of mTORC1. PMID: 29187279 [PubMed - as supplied by publisher] (Source: BMB Reports)
Source: BMB Reports - October 30, 2017 Category: Biochemistry Authors: Ali M, Bukhari SA, Ali M, Lee HW Tags: BMB Rep Source Type: research

Identification of specifically activated angiogenic molecules in HMGB-1-induced angiogenesis.
In this study, we performed time-dependent DNA microarray analysis of endothelial cells (ECs) after HMGB-1 or VEGF treatment. The pathway analysis of each gene set upregulated by HMGB-1 or VEGF showed that most HMGB-1-induced angiogenic pathways were also activated by VEGF, although the activation time and gene sets belonging to the pathways differed. In addition, HMGB-1 upregulated some VEGFR signaling-related angiogenic factors including EGR1 and, importantly, novel angiogenic factors, such as ABL2, CEACAM1, KIT, and VIPR1, which are reported to independently promote angiogenesis under physiological and pathological cond...
Source: BMB Reports - October 25, 2017 Category: Biochemistry Authors: Kim WK, Kwon Y, Park M, Yun S, Kwon JY, Kim H Tags: BMB Rep Source Type: research

Gastrin-releasing peptide promotes the migration of vascular smooth muscle cells through upregulation of matrix metalloproteinase-2 and -9.
We report that GRP significantly enhanced the proliferation and migration of rat VSMCs. GRP increased mRNA and protein expression of matrix metalloproteinase-2 and -9 (MMP-2/9) in VSMCs. The induction of MMP-2/9 by GRP was regulated by the activation of the signal transducer and activator of transcription-3 (STAT-3). In addition, STAT3-knockdown of VSMCs by siRNA or blockade of the GRP receptor inhibited GRP-induced migration of VSMCs. Taken together, our findings indicate that GRP promotes the migration of VSMCs through upregulation of MMP-2/9 via STAT3 activation. PMID: 29065966 [PubMed - as supplied by publisher] (Source: BMB Reports)
Source: BMB Reports - October 25, 2017 Category: Biochemistry Authors: Park HJ, Kim MK, Kim Y, Bae SS, Kim HJ, Bae SK, Bae MK Tags: BMB Rep Source Type: research

PD-1 deficiency protects experimental colitis via alteration of gut microbiota.
Abstract Programmed cell death-1 (PD-1) is a coinhibitory molecule and plays a pivotal role in immune regulation. Here, we demonstrate a role for PD-1 in pathogenesis of inflammatory bowel disease (IBD). Wild-type (WT) mice had severe wasting disease during experimentally induced colitis, while mice deficient for PD-1 (PD-1-/-) did not develop colon inflammation. Interestingly, PD-1-/- mice cohoused with WT mice became susceptible to colitis, suggesting that resistance of PD-1-/- mice to colitis is dependent on their gut microbiota. 16S rRNA gene-pyrosequencing analysis showed that PD-1-/- mice had altered composi...
Source: BMB Reports - October 25, 2017 Category: Biochemistry Authors: Park SJ, Kim JH, Song MY, Sung YC, Lee SW, Park Y Tags: BMB Rep Source Type: research

Protein tyrosine phosphatase PTPN21 acts as a negative regulator of ICAM-1 by dephosphorylating IKK β in TNF-α-stimulated human keratinocytes.
Protein tyrosine phosphatase PTPN21 acts as a negative regulator of ICAM-1 by dephosphorylating IKKβ in TNF-α-stimulated human keratinocytes. BMB Rep. 2017 Oct 25;: Authors: Cho YC, Kim BR, Cho S Abstract Intercellular adhesion molecule-1 (ICAM-1), which is induced by tumor necrosis factor (TNF)-α, contributes to the entry of immune cells into the site of inflammation in the skin. Here, we show that protein tyrosine phosphatase non-receptor type 21 (PTPN21) negatively regulates ICAM-1 expression in human keratinocytes. PTPN21 expression was transiently induced after stimulation with T...
Source: BMB Reports - October 25, 2017 Category: Biochemistry Authors: Cho YC, Kim BR, Cho S Tags: BMB Rep Source Type: research

Antioxidant Effects of Selenocysteine on Replicative Senescence in Human Adipose-Derived Mesenchymal Stem Cells.
Abstract In most clinical applications, human mesenchymal stem cells (hMSCs) are expanded in large scale before their administration. Prolonged culture in vitro results in cellular senescence-associated phenotypes, including accumulation of reactive oxygen species (ROS) and decreased cell viabilities. Profiling of stem cell-related genes during in vitro expansion revealed that numerous canonical pathways were significantly changed. To determine the effect of selenocysteine (Sec), a rare amino acid found in several antioxidant enzymes, on the replicative senescence in hMSCs, we treated senescent hMSCs with Sec. Sup...
Source: BMB Reports - October 25, 2017 Category: Biochemistry Authors: Suh N, Lee EB Tags: BMB Rep Source Type: research

Zinc finger Protein 143 expression is closely related to tumor malignancy via regulating cell motility in breast cancer.
Abstract We previously reported the involvement of zinc-finger protein 143(ZNF143) on cancer cell motility in colon cancer cells. Here, ZNF143 was further characterized in breast cancer. Immunohistochemistry was used to determine the expression of ZNF143 in normal tissues and in tissues from metastatic breast cancer at various stages. Notably, ZNF143 was selectively expressed in duct and gland epithelium of normal breast tissues, which decreased when the tissue became malignant. To determine the molecular mechanism how ZNF143 affects breast cancer progression, it was knocked down by infecting benign breast cancer ...
Source: BMB Reports - October 25, 2017 Category: Biochemistry Authors: Paek AR, Mun JY, Hong KM, Lee J, Hong DW, You HJ Tags: BMB Rep Source Type: research

Anti-inflammatory and anti-oxidative effects of 3-(naphthalen-2-yl(propoxy)methyl)azetidine hydrochloride on β-amyloid-induced microglial activation.
Anti-inflammatory and anti-oxidative effects of 3-(naphthalen-2-yl(propoxy)methyl)azetidine hydrochloride on β-amyloid-induced microglial activation. BMB Rep. 2017 Oct 25;: Authors: Yang SJ, Kim J, Lee SE, Ahn JY, Choi SY, Cho SW Abstract We aimed to assess the anti-inflammatory and antioxidative properties of KHG26792, a novel azetidine derivative, in amyloid β (Aβ)-treated primary microglial cells. KHG26792 attenuated the Aβ-induced production of inflammatory mediators such as IL-6, IL-1β, TNF-α, and nitric oxide. The levels of protein oxidation, lipid peroxidation, RO...
Source: BMB Reports - October 25, 2017 Category: Biochemistry Authors: Yang SJ, Kim J, Lee SE, Ahn JY, Choi SY, Cho SW Tags: BMB Rep Source Type: research

Hypoxia suffocates histone demethylases to change gene expression: a metabolic control of histone methylation.
Abstract Hypoxia affects various physiological and pathophyological processes. Hypoxia changes the expression of the hypoxia-responsive genes through two main pathways. First, hypoxia activates transcription factors (TF) such as Hypoxia-inducible Factor (HIF). Second, hypoxia decreases the activity of Jumonji C domain-containing histone demethylases (JMJDs) that require O2 and α-Ketoglutarate (α-KG) as substrates. The JMJDs affect gene expression through their regulation of the active or repressive histone methylations. We conducted profiling of H3K4me3, H3K9me3, and H3K27me3 under both normoxia and hy...
Source: BMB Reports - October 25, 2017 Category: Biochemistry Authors: Park H Tags: BMB Rep Source Type: research

Pro-tumorigenic roles of TGF- β signaling during the early stages of liver tumorigenesis through upregulation of Snail.
Pro-tumorigenic roles of TGF-β signaling during the early stages of liver tumorigenesis through upregulation of Snail. BMB Rep. 2017 Oct 25;: Authors: Moon H, Han KH, Ro SW Abstract Many studies have focused on the tumor suppressive role of TGF-β signaling during the early stages of tumorigenesis by activating the target genes involved in cytostasis and apoptosis. We investigated the effects of TGF-β inhibition on early tumorigenesis in the liver, by employing diverse inhibitory methods. Strikingly, TGF-β inhibition consistently suppressed hepatic tumorigenesis that was induced eit...
Source: BMB Reports - October 25, 2017 Category: Biochemistry Authors: Moon H, Han KH, Ro SW Tags: BMB Rep Source Type: research

Airborne particulate matter increases MUC5AC expression by downregulating Claudin-1 expression in human airway cells.
Abstract CLB2.0, a constituent of PM, induces secretion of multiple cytokines and chemokines that regulate airway inflammation. Specifically, IL-6 upregulates CLB2.0-induced MUC5AC and MUC1 expression. Interestingly, of the tight junction proteins examined, claudin-1 expression was inhibited by CLB2.0. While the overexpression of claudin-1 decreased CLB2.0-induced MUC5AC expression, it increased the expression of the anti-inflammatory mucin, MUC1. CLB2.0-induced IL-6 secretion was mediated by ROS. The ROS scavenger N-acetyl-cysteine inhibited CLB2.0-induced IL-6 secretion, thereby decreasing the CLB2.0-induced MUC...
Source: BMB Reports - September 26, 2017 Category: Biochemistry Authors: Kim SS, Kim CH, Kim JW, Kung HC, Park TW, Shin YS, Kim JD, Ryu S, Kim WJ, Choi YH, Song KS Tags: BMB Rep Source Type: research

LDB2 regulates the expression of DLL4 through the formation of oligomeric complexes in endothelial cells.
Abstract Delta-like ligand 4 (DLL4) expression in endothelial cells is intimately associated with angiogenic sprouting and vascular remodeling, but the precise mechanism of transcriptional regulation of DLL4 remains incompletely understood. Here, we showed that LIM-domain binding protein 2 (LDB2) plays an important role in regulating basal DLL4 and VEGF-induced DLL4 expression. Knockdown of LDB2 using siRNA enhanced endothelial sprouting and tubular network formation in vitro. Injection of ldb2-morpholino resulted in defective development of intersegmental vessels in zebrafish. Reduction or overexpression of LDB2 ...
Source: BMB Reports - September 26, 2017 Category: Biochemistry Authors: Choi HJ, Rho SS, Choi DH, Kwon YG Tags: BMB Rep Source Type: research

An NMR Study on the Intrinsically Disordered Core Transactivation Domain of Human Glucocorticoid Receptor.
Abstract A large number of transcriptional activation domains (TADs) are intrinsically unstructured, meaning they are devoid of a three-dimensional structure. The fact that these TADs are transcriptionally active without forming a 3-D structure raises the question of what features in these domains enable them to function. One of two TADs in human glucocorticoid receptor (hGR) is located at its N-terminus and is responsible for ~70% of the transcriptional activity of hGR. This 58-residue intrinsically-disordered TAD, named tau1c in an earlier study, was shown to form three helices under trifluoroethanol, which migh...
Source: BMB Reports - September 26, 2017 Category: Biochemistry Authors: Kim DH, Wright A, Han KH Tags: BMB Rep Source Type: research

DNA methylation-based age prediction from various tissues and body fluids.
Abstract Aging is a natural and gradual process in human life. It is influenced by heredity, environment, lifestyle, and disease. DNA methylation varies with age, and the ability to predict the age of donor using DNA from evidence materials at a crime scene is of considerable value in forensic investigations. Recently, many studies have reported age prediction models based on DNA methylation from various tissues and body fluids. Those models seem to be very promising because of their high prediction accuracies. In this review, the changes of age-associated DNA methylation and the age prediction models for various ...
Source: BMB Reports - September 26, 2017 Category: Biochemistry Authors: Jung SE, Shin KJ, Lee HY Tags: BMB Rep Source Type: research

Rules for functional microRNA targeting.
Abstract MicroRNAs (miRNAs) are ~22nt-long single-stranded RNA molecules that form a RNA-induced silencing complex with Argonaute (AGO) protein to post-transcriptionally downregulate their target messenger RNAs (mRNAs). To understand the regulatory mechanisms of miRNA, discovering the underlying functional rules for how miRNAs recognize and repress their target mRNAs is of utmost importance. To determine functional miRNA targeting rules, previous studies extensively utilized various methods including high-throughput biochemical assays and bioinformatics analyses. However, targeting rules reported in one study ofte...
Source: BMB Reports - September 26, 2017 Category: Biochemistry Authors: Kim D, Chang HR, Baek D Tags: BMB Rep Source Type: research

Heterogeneous interaction network of yeast prions and remodeling factors detected in live cells.
Abstract Budding yeast has dozens of prions, which are mutually dependent on each other for the de novo prion formation. In addition to the interactions among prions, transmissions of prions are strictly dependent on two chaperone systems: the Hsp104 and the Hsp70/Hsp40 (J-protein) systems, both of which cooperatively remodel the prion aggregates to ensure the multiplication of prion entities. Since it has been postulated that prions and the remodeling factors constitute complex networks in cells, a quantitative approach to describe the interactions in live cells would be required. Here, the researchers applied du...
Source: BMB Reports - September 12, 2017 Category: Biochemistry Authors: Pack CG, Inoue Y, Higurashi T, Kawai-Noma S, Hayashi D, Craig E, Taguchi H Tags: BMB Rep Source Type: research

Dual effects of a CpG-DNAzyme targeting mutant EGFR transcripts in lung cancer cells: TLR9 activation and EGFR downregulation.
Abstract Non-small-cell lung cancer (NSCLC) is commonly caused by a mutation in the epidermal growth factor receptor (EGFR) and subsequent aberrant EGFR signaling with uncontrolled kinase activity. A deletion mutation in EGFR exon 19 is frequently observed in EGFR gene mutations. We designed a DNAzyme to suppress the expression of mutant EGFR by cleaving the mutant EGFR mRNA. The DNAzyme (named Ex19del Dz) specifically cleaved target RNA and decreased cancer cell viability when transfected into gefitinib-resistant lung cancer cells harboring EGFR exon 19 deletions. The DNAzyme decreased EGFR expression and inhibit...
Source: BMB Reports - September 12, 2017 Category: Biochemistry Authors: Jang D, Baek YM, Park H, Hwang YE, Kim DE Tags: BMB Rep Source Type: research

Peroxiredoxin I participates in the protection of reactive oxygen species-mediated cellular senescence.
Abstract Peroxiredoxin I (Prx I) plays an important role as a reactive oxygen species (ROS) scavenger in protecting and maintaining cellular homeostasis; however, the underlying mechanisms are not well understood. Here, we identified a critical role of Prx I in protecting cells against ROS-mediated cellular senescence by suppression of p16INK4a expression. Compared to wild-type mouse embryonic fibroblasts (WT-MEFs), Prx I-/- MEFs exhibited senescence-associated phenotypes. Moreover, the aged Prx I-/- mice showed an increased number of cells with senescence associated-β-galactosidase (SA-β-gal) activity i...
Source: BMB Reports - September 12, 2017 Category: Biochemistry Authors: Park YH, Kim HS, Lee JH, Choi SA, Kim JM, Oh GT, Kang SW, Kim SU, Yu DY Tags: BMB Rep Source Type: research

Fibronectin expression is upregulated by PI-3K/Akt activation in tamoxifen-resistant breast cancer cells.
Abstract Fibronectin (FN) plays important roles in the EMT in a variety of cancer cell types. However, the mechanism by which FN expression is regulated in tamoxifen-resistant (TamR) breast cancer cells has not yet been fully elucidated. Aberrant FN expression was associated with poor prognosis in patients with luminal type A breast cancer. In addition, FN was upregulated in TamR cells. To investigate the mechanism by which FN expression is regulated, we assessed the levels of phosphorylated Akt, JNK, and STAT3 and found that they were all increased in TamR cells. Induction of FN expression was dampened by LY29400...
Source: BMB Reports - August 31, 2017 Category: Biochemistry Authors: You D, Jung SP, Jeong Y, Bae SY, Lee JE, Kim S Tags: BMB Rep Source Type: research

Bach2represses the AP-1-driven induction of interleukin-2 gene transcription in CD4+ T cells.
Abstract The transcription repressor Bach2 has been proposed as a regulator of T cell quiescence, but the underlying mechanism is not fully understood. Given the importance of interleukin-2 in T cell activation, we investigated whether Bach2 is a component of the network of factors that regulates interleukin-2 expression. In primary and transformed CD4+ T cells, Bach2 overexpression counteracted T cell receptor/CD28- or PMA/ionomycin-driven induction of interleukin-2 expression, and silencing of Bach2 had the opposite effect. Luciferase and chromatin immunoprecipitation assays revealed that Bach2 binds to multiple...
Source: BMB Reports - August 31, 2017 Category: Biochemistry Authors: Jang E, Lee HR, Lee GH, Oh AR, Cha JY, Igarashi K, Youn J Tags: BMB Rep Source Type: research

FGF Signaling: Diverse Roles During Cochlear Development.
Abstract Mammalian inner ear comprises of six sensory organs; cochlea, utricle, saccule, and three semicircular canals. The cochlea contains sensory epithelium known as the organ of Corti which senses sound through mechanosensory hair cells. Mammalian inner ear undergoes series of morphogenesis during development by beginning thickening of ectoderm nearby hindbrain. These events require tight regulation of multiple signaling cascades including FGF, Wnt, Notch and Bmp signaling. In this review, we will discuss the role of newly emerging signaling, FGF signaling, for its roles required for cochlear development. ...
Source: BMB Reports - August 31, 2017 Category: Biochemistry Authors: Ebeid M, Huh SH Tags: BMB Rep Source Type: research

CoMIC, the hidden dynamics of mitochondrial inner compartments.
Abstract Mitochondria have evolutionarily, functionally and structurally distinct outer- (OMM) and inner-membranes (IMM). Thus, mitochondrial morphology is controlled by independent but coordinated activity of fission and fusion of the OMM and IMM. Constriction and division of the OMM are mediated by endocytosis-like machineries, which include dynamin-related protein 1 with additional cytosolic vesicle scissoring machineries such as actin filament and Dynamin 2. However, structural alteration of the IMM during mitochondrial division has been poorly understood. Recently, we found that the IMM and the inner compartm...
Source: BMB Reports - August 14, 2017 Category: Biochemistry Authors: Cho B, Sun W Tags: BMB Rep Source Type: research

Two distinct nodes of translational inhibition in the Integrated Stress Response.
Abstract The Integrated Stress Response (ISR) refers to a signaling pathway initiated by stress-activated eIF2α kinases. Once activated, the pathway causes attenuation of global mRNA translation while also paradoxically inducing stress response gene expression. A detailed analysis of this pathway has helped us better understand how stressed cells coordinate gene expression at translational and transcriptional levels. The translational attenuation associated with this pathway has been largely attributed to the phosphorylation of the translational initiation factor eIF2α. However, independent studies are...
Source: BMB Reports - August 14, 2017 Category: Biochemistry Authors: Ryoo HD, Vasudevan D Tags: BMB Rep Source Type: research

Identification of simvastatin-regulated targets associated with JNK activation in DU145 human prostate cancer cell death signaling.
In this study, our results showed that the c-Jun N-terminal kinase (JNK) activation was associated with the enhancement of docetaxel-induced cytotoxicity by simvastatin in DU145 human prostate cancer cells. To better understand the basic molecular mechanisms, we investigated simvastatin-regulated targets during simvastatin-induced cell death in DU145 cells using two-dimensional (2D) proteomic analysis. Thus, vimentin, Ras-related protein Rab-1B (RAB1B), cytoplasmic hydroxymethylglutaryl-CoA synthase (cHMGCS), thioredoxin domain-containing protein 5 (TXNDC5), heterogeneous nuclear ribonucleoprotein K (hnRNP K), N-myc downst...
Source: BMB Reports - August 11, 2017 Category: Biochemistry Authors: Jung EJ, Chung KH, Kim CW Tags: BMB Rep Source Type: research

Caspase-2 mediates triglyceride (TG)-induced macrophage cell death.
Abstract Triglyceride (TG) accumulation causes macrophage cell death, which affects the development of atherosclerosis. Here, we examined whether caspase-2 is implicated in TG-induced macrophage cell death. We found that caspase-2 activity is increased in TG-treated THP-1 macrophages, and that inhibition of caspase-2 activity drastically inhibits TG-induced cell death. We previously reported that TG-induced macrophage death is triggered by caspase-1, and thus investigated the relationship between casapse-2 and caspase-1 in TG-induced macrophage cell death. Inhibition of caspase-2 activity decreased caspase-1 activ...
Source: BMB Reports - August 3, 2017 Category: Biochemistry Authors: Lim J, Kim SH, Kim HK, Rhee KJ, Kim YS Tags: BMB Rep Source Type: research

Dead cell phagocytosis and innate immune checkpoint.
Abstract Human body are losing several billions of cells every day. When cells are dying in vivo, the corpse of dead cell are not remained uncleared. Dead cells are efficiently recognized and cleared by multiple types of neighboring phagocytes. In the initial researches studying cell death, molecular mechanisms regulating cell death are more focused and the end corpse are simply considered as cellular debris. However, it has been revealed that various biological influences after cell death are important for the followed immune regulations. Healthy clearance of normal dead cells is silently carried out with immune ...
Source: BMB Reports - August 3, 2017 Category: Biochemistry Authors: Yoon KW Tags: BMB Rep Source Type: research

Transforming growth factor β1 enhances adhesion of endometrial cells to mesothelium by regulating integrin expression.
Transforming growth factor β1 enhances adhesion of endometrial cells to mesothelium by regulating integrin expression. BMB Rep. 2017 Aug 01;: Authors: Choi HJ, Park MJ, Kim BS, Choi HJ, Joo B, Lee KS, Choi JH, Chung TW, Ha KT Abstract Interestingly, transforming growth factor β1 (TGF-β1) expression was higher in endometriotic epithelial cells than in normal endometrial cells. The adhesion efficiency of endometriotic epithelial cells to mesothelial cells was also higher than that of normal endometrial cells. Moreover, TGF-β1 directly induced the adhesion of endometrial cells to meso...
Source: BMB Reports - August 1, 2017 Category: Biochemistry Authors: Choi HJ, Park MJ, Kim BS, Choi HJ, Joo B, Lee KS, Choi JH, Chung TW, Ha KT Tags: BMB Rep Source Type: research

Effects of PEP-1-FK506BP on cyst formation in polycystic kidney disease.
In this study, we determined the roles of PEP-1-FK506BP on cell proliferation and cyst formation in PKD cells. Purified PEP-1-FK506BP transduced into PKD cells and markedly inhibited cell proliferation. Also, PEP-1-FK506BP drastically inhibited the expression levels of p-Akt, p-p70S6K, p-mTOR, and p-ERK in PKD cells. In a 3D culture system, PEP-1-FK506BP significantly reduced cyst formation. Furthermore, the combined effects of rapamycin and PEP-1-FK506BP on cyst formation were markedly higher than those of individual treatments. These results suggest that the PEP-1-FK506BP delays cyst formation and could be a new therapeu...
Source: BMB Reports - July 28, 2017 Category: Biochemistry Authors: Jo HS, Eum WS, Park EY, Ko JY, Kim DY, Kim DW, Shin MJ, Son O, Cho SB, Park JH, Lee CH, Yeo EJ, Yeo HJ, Choi YJ, Youn JK, Cho SW, Park J, Park JH, Choi SY Tags: BMB Rep Source Type: research

Neuropeptide Y improves cisplatin-induced bone marrow dysfunction without blocking chemotherapeutic efficacy in a cancer mouse model.
Abstract Cisplatin is the most effective and widely used chemotherapeutic agent for many types of cancer. Unfortunately, its clinical use is limited by its adverse effects, notably bone marrow suppression leading to abnormal hematopoiesis. We previously revealed that neuropeptide Y (NPY) is responsible for the maintenance of hematopoietic stem cell (HSC) function by protecting the sympathetic nervous system (SNS) fibers survival from chemotherapy-induced bone marrow impairment. Here, we show the NPY-mediated protective effect against bone marrow dysfunction due to cisplatin in an ovarian cancer mouse model. During...
Source: BMB Reports - July 17, 2017 Category: Biochemistry Authors: Park MH, Jung IK, Min WK, Choi JH, Kim GM, Jin HK, Bae JS Tags: BMB Rep Source Type: research

SRSF2 directly inhibits intron splicing to suppresses cassette exon inclusion.
Abstract SRSF2, a Serine-Arginine rich (SR) protein, is a splicing activator that mediates exon inclusion and exclusion events equally well. Here we show SRSF2 directly suppresses intron splicing to suppress cassette exon inclusion in SMN pre-mRNA. Through a serial mutagenesis, we demonstrate that a 10 nt RNA sequence surrounding the branch-point (BP), is important for SRSF2-mediated inhibition of cassette exon inclusion through directly interacting with SRSF2. We conclude that SRSF2 inhibits intron splicing to promote exon exclusion. PMID: 28712387 [PubMed - as supplied by publisher] (Source: BMB Reports)
Source: BMB Reports - July 17, 2017 Category: Biochemistry Authors: Moon H, Cho S, Loh TJ, Jang HN, Liu Y, Choi N, Oh J, Ha J, Zhou J, Cho S, Kim DE, Ye MB, Zheng X, Shen H Tags: BMB Rep Source Type: research

RING E3 ligases: key regulatory elements are involved in abiotic stress responses in plants.
Abstract Plants are constantly exposed to a variety of abiotic stresses, such as drought, heat, cold, flood, and salinity. To survive under such unfavorable conditions, plants have evolutionarily developed their own resistant-mechanisms. For several decades, many studies have clarified specific stress response pathways of plants through various molecular and genetic studies. In particular, it was recently discovered that ubiquitin proteasome system (UPS), a regulatory mechanism for protein turn over, is greatly involved in the stress responsive pathways. In the UPS, many E3 ligases play key roles in recognizing an...
Source: BMB Reports - July 17, 2017 Category: Biochemistry Authors: Cho SK, Ryu MY, Kim JH, Hong JS, Oh TR, Kim WT, Yang SW Tags: BMB Rep Source Type: research

Rescuing p53 from mdm2 by intrinsically unfolded SUMO protease 4.
Abstract Many intrinsically unstructured/unfolded proteins (IUPs) contain transient local secondary structures even though they are "unstructured" in a tertiary sense. These local secondary structures are named "pre-structured motifs (PreSMos)" and in fact are the specificity determinants for IUP-target binding, i.e., the active sites in IUPs. Using high-resolution NMR we have delineated a PreSMo active site in the intrinsically unfolded mid-domain (residues 201-300) of SUMO-specific protease 4 (SUSP4). This 29-residue motif which we termed a p53 rescue motif can protect p53 from mdm2 quenching...
Source: BMB Reports - July 17, 2017 Category: Biochemistry Authors: Kim DH, Lee C, Kim B, Lee SH, Han KH Tags: BMB Rep Source Type: research

Large-scale human-yeast genetic interaction for construction of disease network: systematic discovery of multiple drug targets.
Abstract A novel approach has been used to identify functional interactions relevant to human disease. Using high-throughput human-yeast genetic interaction screens, a first draft of disease interactome was obtained. This was achieved by firstly searching for candidate human disease genes that confer toxicity in yeast, and secondly identifying modulators of this toxicity. The study found potentially disease-relevant interactions by analyzing the network of functional interactions and focusing on genes implicated in amyotrophic lateral sclerosis (ALS), for instance. In the subsequent proof-of-concept study focused ...
Source: BMB Reports - July 7, 2017 Category: Biochemistry Authors: Suk K Tags: BMB Rep Source Type: research

Suppression of SIRT2 and altered acetylation status of human pluripotent stem cells: possible link to metabolic switch during reprogramming.
Abstract Primed human pluripotent stem cells (hPSCs) are highly dependent on glycolysis rather than oxidative phosphorylation, which is similar to the metabolic switch that occurs in cancer cells. However, the molecular mechanisms that underlie this metabolic reprogramming in hPSCs and its relevance to pluripotency remain unclear. Cha et al. (2017) recently revealed that downregulation of SIRT2 by miR-200c enhances acetylation of glycolytic enzymes and glycolysis, which in turn facilitates cellular reprogramming, suggesting that SIRT2 is a key enzyme linking the metabolic switch and pluripotency in hPSCs. PMI...
Source: BMB Reports - July 7, 2017 Category: Biochemistry Authors: Kwon OS, Han MJ, Cha HJ Tags: BMB Rep Source Type: research

Survival of APC-mutant colorectal cancer cells requires interaction between tankyrase and a thiol peroxidase peroxiredoxin II.
Abstract Overexpression of mammalian 2-Cys peroxiredoxin (Prx) enzymes is observed in most cancer tissues. Nevertheless, their specific role in colorectal cancer progression has yet to be fully elucidated. Here, a novel molecular mechanism by which PrxII/TNKS interaction mediates survival of APC-mutant CRC cells was explored. In mice with inactivating APC mutation, a model of spontaneous intestinal tumorigenesis, deletion of PrxII reduces intestinal adenomatous polyposis and thereby increases survival. In APC mutation-derived human CRC cells, PrxII depletion hinders the PARP-dependent Axin1 degradation through TNK...
Source: BMB Reports - July 7, 2017 Category: Biochemistry Authors: Kang DH, Lee JHS, Kang SW Tags: BMB Rep Source Type: research

Repression of the F-box protein Skp2 is essential for actin damage-induced tetraploid G1 arrest.
In this study, we investigated a role of Skp2, which targets CDK2 inhibitor p27/Kip1, in actin damage-induced tetraploid G1 arrest. Expression of Skp2 was decreased, but p27/Kip1 was increased after actin damage-induced cytokinesis blockade. The roles of Skp2 repression in tetraploid G1 arrest was investigated by analyzing the effects of ectopic expression of Skp2. After actin damage, ectopic expression of Skp2 resulted in DNA synthesis and accumulation of multinucleated cells, and eventually induced apoptosis. These results suggest that Skp2 repression is important for sustaining the tetraploid G1 arrest after cytokinesis...
Source: BMB Reports - June 26, 2017 Category: Biochemistry Authors: Jo Y, Shin DY Tags: BMB Rep Source Type: research

ER membrane protein complex subunit 6 (EMC6) is a novel tumor suppressor in gastric cancer.
Abstract Endoplasmic reticulum (ER) membrane protein complex subunit 6 (EMC6) is a novel human autophagy-related molecule. Here, using tissue microarray and immunohistochemistry, we report that EMC6 protein is lost or reduced in glandular cells of patients with gastric adenocarcinoma, compared to normal stomach mucosa. Overexpression of EMC6 in gastric cancer cells inhibited cell growth, migration, and invasion, and induced apoptosis and cell cycle arrest at S-phase. Further investigation suggested that EMC6 overexpression in BGC823 cells reduced tumorigenicity in a xenograft model, demonstrating that EMC6 has the...
Source: BMB Reports - June 26, 2017 Category: Biochemistry Authors: Wang X, Xia Y, Xu C, Lin X, Xue P, Zhu S, Bai Y, Chen Y Tags: BMB Rep Source Type: research

Emerging Roles of Protein Disulfide Isomerase in Cancer.
Abstract Protein disulfide isomerase (PDI) family is a group of multifunctional endoplasmic reticulum (ER) enzymes mediating the formation of disulfide bonds, catalyzing the cysteine-based redox reactions and assisting the quality control of the client proteins. Recent structural and functional studies have demonstrated that PDI members not only play an essential role in the proteostasis in the ER but also exert diverse effects in numerous human diseases including cancer and neurodegenerative diseases. Increasing evidence suggests that PDI is actively involved in the proliferation, survival, and metastasis of seve...
Source: BMB Reports - June 26, 2017 Category: Biochemistry Authors: Lee E, Lee DH Tags: BMB Rep Source Type: research

Functional roles of CTCF in breast cancer.
Abstract CTCF, Zn-finger protein, has been identified as multifunctional transcription factor to regulate gene expression through recruitment of other co-activators and binding to promoter regions of target genes. Furthermore, it has been proposed as an insulator protein that contributes to the establishment of functional three-dimensional chromatin structures. It could disrupt transcription through block the connection between enhancer and promoter. Previous studies revealed that various diseases including breast cancer were developed from aberrant expression of CTCF itself or their target genes. In this review, ...
Source: BMB Reports - June 26, 2017 Category: Biochemistry Authors: Oh S, Oh C, Yoo KH Tags: BMB Rep Source Type: research

Kahweol Inhibits Lipid Accumulation and Induces Glucose-Uptake Through Activation of AMP-Activated Protein Kinase (AMPK).
Abstract Weight loss ≥5% is sufficient to significantly reduce health risks for people with obesity; therefore, development of novel weight loss compounds with reduced toxicity is urgently required. After screening of natural compounds with anti-adipogenesis properties in 3T3-L1 cells, we determined that kahweol, a coffee-specific diterpene, inhibited adipogenesis. Kahweol reduced lipid accumulation and expression levels of adipogenesis and lipid accumulation-related factors. Levels of Phosphorylated AKT and phosphorylated JAK2, which induce lipid accumulation, decreased in kahweol-treated cells. Notably, kahwe...
Source: BMB Reports - June 12, 2017 Category: Biochemistry Authors: Baek JH, Kim NJ, Song JK, Chun KH Tags: BMB Rep Source Type: research

Cytoprotective effect exerted by geraniin in HepG2 cells is through microRNA mediated regulation of BACH-1 and HO-1.
Abstract Geraniin, a hydrolysable tannin, used in traditional medicine in Southeast Asia, is known to exhibit various biological activities. As an antioxidant it is known to up-regulate phase II enzyme Heme oxygenase-1 (HO-1). However its mechanism is not clearly understood. Nuclear factor erythroid-derived 2 related factor 2 (Nrf-2) is transcriptionally up-regulated by Extracellular signal-regulated kinase (ERK) 1/2 and retained in nucleus due to inactivated Glycogen synthase kinase 3 beta (GSK-3β). Geraniin additionally down-regulates expression of microRNA 217 and 377 (miR-217 and miR-377) which target HO-...
Source: BMB Reports - June 12, 2017 Category: Biochemistry Authors: Aayadi H, Mittal SPK, Deshpande A, Gore M, Ghaskadbi SS Tags: BMB Rep Source Type: research

Endothelial miR-26a regulates VEGF-Nogo-B receptor-mediated angiogenesis.
Abstract The Nogo-B receptor (NgBR) is necessary for not only Nogo-B-mediated angiogenesis but also vascular endothelial growth factor (VEGF)-induced angiogenesis. However, the molecular mechanisms underlying the regulatory role of the VEGF-NgBR axis in angiogenesis are not fully understood. Here, we report that miR-26a serves as a critical regulator of VEGF-mediated angiogenesis through directly targeting NgBR in endothelial cells (ECs). Stimulation of ECs by VEGF increased the expression of NgBR and decreased the expression of miR-26a. In addition, miR-26a decreased the VEGF-induced migration and proliferation o...
Source: BMB Reports - June 12, 2017 Category: Biochemistry Authors: Jo HN, Kang H, Lee A, Choi J, Chang W, Lee MS, Kim J Tags: BMB Rep Source Type: research

Structure, signaling and the drug discovery of the Ras oncogene protein.
Abstract Mutations in Ras GTPase are among the most common genetic alterations in human cancers. Despite extensive research investigating Ras proteins, their functions still remain a challenge over a long period of time. The currently available data suggests that solving the outstanding issues regarding Ras could lead to development of effective drugs that could have a significant impact on cancer treatment. Developing a better understanding of their biochemical properties or modes of action, along with improvements in their pharmacologic profiles, clinical design and scheduling will enable the development of more...
Source: BMB Reports - June 2, 2017 Category: Biochemistry Authors: Han CW, Jeong MS, Jang SB Tags: BMB Rep Source Type: research

Dual TORCs driven and B56 orchestrated Signaling Network guides eukaryotic cell migration.
Abstract Different types of eukaryotic cells may adopt seemingly distinct modes of directional cell migration. However, several core aspects are regarded common whether the movement is either ameoboidal or mesenchymal. The region of cells facing the attractive signal is often termed leading edge where lamellipodial structures dominates and the other end of the cell called rear end is often mediating cytoskeletal F-actin contraction involving Myosin-II. Dynamic remodeling of cell-to-matrix adhesion involving integrin is also evident in many types of migrating cells. All these three aspects of cell migration are sig...
Source: BMB Reports - June 2, 2017 Category: Biochemistry Authors: Kim LW Tags: BMB Rep Source Type: research