Up-regulation of HOXB cluster genes are epigenetically regulated in tamoxifen-resistant MCF7 breast cancer cells.
Abstract Tamoxifen (TAM) is commonly used to treat estrogen receptor (ER)-positive breast cancer. Despite the remarkable benefits, resistance to TAM presents a serious therapeutic challenge. Since several HOX transcription factors have been proposed as strong candidates in the development of resistance to TAM therapy in breast cancer, we generated an in vitro model of acquired TAM resistance using ER-positive MCF7 breast cancer cells (MCF7-TAMR), and analyzed the expression pattern and epigenetic states of HOX genes. HOXB cluster genes were uniquely up-regulated in MCF7-TAMR cells. Survival analysis of in slico da...
Source: BMB Reports - May 28, 2018 Category: Biochemistry Authors: Yang S, Lee JY, Hur H, Oh JH, Kim MH Tags: BMB Rep Source Type: research
29-kDa FN-f inhibited autophagy through modulating localization of HMGB1 in human articular chondrocytes.
In this study, we investigated whether changes induced by 29-kDa amino-terminal fibronectin fragment (29-kDa FN-f) in HMGB1 expression influences the pathogenesis of OA via an HMGB1-modulated autophagy signaling pathway. Human articular chondrocytes were enzymatically isolated from articular cartilage. The level of mRNA was measured by quantitative real-time PCR. The expression of proteins was examined by western blot analysis, immnunofluorescence assay, and enzyme-linked immunosorbent assay. Interaction of proteins was evaluated by immunoprecipitation. The HMGB1 level was significantly lower in human OA cartilage than in ...
Source: BMB Reports - May 28, 2018 Category: Biochemistry Authors: Hwang HS, Choi MH, Kim HA Tags: BMB Rep Source Type: research
Anti-inflammatory effects of a novel compound, MPQP, through the inhibition of IRAK1 signaling pathways in LPS-stimulated RAW 264.7 macrophages.
In this study, we found a novel anti-inflammatory compound, 1-[(2R,4S)-2-methyl-4-(phenylamino)-1,2,3,4-tetrahydroquinolin-1-yl]prop-2-en-1-one (MPQP). It showed strong anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. These effects were exerted through the inhibition of the production of NO and pro-inflammatory cytokines, such as interleukin (IL)-6, IL-1β, and tumor necrosis factor-α (TNF-α). Furthermore, MPQP decreased the expression levels of inducible NO synthase (iNOS) and cyclooxygenase 2 (COX-2). Additionally, it mediated the inhibition of the phosphorylation of...
Source: BMB Reports - May 28, 2018 Category: Biochemistry Authors: Kim BR, Cho YC, Cho S Tags: BMB Rep Source Type: research
MiR-204 acts as a potential therapeutic target in acute myeloid leukemia by increasing BIRC6-mediated apoptosis.
Abstract Acute myeloid leukemia (AML) is one of the most common hematological malignancies all around the world. MicroRNAs have been determined to contribute various cancers initiation and progression, including AML. Although microRNA-204 (miR-204) exerts anti-tumor effects in several kinds of cancers, its function in AML remains unknown. In the present study, we assessed miR-204 expression in AML blood samples and cell lines. We also investigated the effects of miR-204 on cellular function of AML cells and the underlying mechanisms of the action of miR-204. Our results showed that miR-204 expression was significa...
Source: BMB Reports - May 16, 2018 Category: Biochemistry Authors: Wang Z, Luo H, Fang Z, Fan Y, Liu X, Zhang Y, Rui S, Chen Y, Hong L, Gao J, Zhang M Tags: BMB Rep Source Type: research
Osteoclast-derived SLIT3 is a coupling factor linking bone resorption to bone formation.
Abstract We identified osteoclast-derived SLIT3 as a new coupling factor using fractionated secretomics. Coupling links bone resorption to bone formation. SLIT3 stimulated the recruitment and proliferation of osteoblasts into bone remodeling sites via activation of β-catenin. Autocrine signaling by SLIT3 also inhibited bone resorption by suppressing the fusion and differentiation of pre-osteoclasts. All mice lacking Slit3 or its receptor Robo1 showed an osteopenic phenotype with low bone formation and high bone resorption. A small truncated recombinant SLIT3 protein increased bone mass in an osteopenic mouse ...
Source: BMB Reports - May 16, 2018 Category: Biochemistry Authors: Koh JM Tags: BMB Rep Source Type: research
Deubiquitinase USP35 as a novel mitotic regulator via maintenance of Aurora B stability.
Abstract Aurora B is an important kinase involved in dynamic cellular events in mitosis. Aurora B activity is controlled by several post-translational modifications (PTMs). Among them, E3 ubiquitin ligase-mediated ubiquitination plays crucial roles in controlling the relocation and degradation of Aurora B. Aurora B, ubiquitinated by different E3 ligases, moves to the exact site for its mitotic function during metaphase-anaphase transition and is then degraded for cell cycle progression at the end of mitosis. However, how the stability of Aurora B is maintained until its degradation has been poorly understood. Rece...
Source: BMB Reports - May 16, 2018 Category: Biochemistry Authors: Park J, Song EJ Tags: BMB Rep Source Type: research
Mitochondria-mediated defense mechanisms against pathogens in Caenorhabditis elegans.
Abstract Mitochondria are crucial organelles that generate cellular energy and metabolites. Recent studies indicate that mitochondria also regulate immunity. In this review, we discuss key roles of mitochondria in immunity against pathogen infection and underlying mechanisms, focusing on discoveries using Caenorhabditis elegans. Various mitochondrial processes, including mitochondrial surveillance mechanisms, mitochondrial unfolded protein response (UPRmt), mitophagy, and reactive oxygen species (ROS) production, contribute to immune responses and resistance of C. elegans against pathogens. Biological processes of...
Source: BMB Reports - May 16, 2018 Category: Biochemistry Authors: Kwon S, Kim EJE, Lee SV Tags: BMB Rep Source Type: research
Cancer stem cell metabolism: target for cancer therapy.
Abstract Increasing evidence suggests that cancer stem cell (CSC) theory represents an important mechanism underlying the observed failure of existing therapeutic modalities to fully eradicate cancers. In addition to their more established role in maintaining minimal residual disease after treatment and forming the new bulk of the tumor, CSCs might also critically contribute to tumor recurrence and metastasis. For this reason, specific elimination of CSCs may thus represent one of the most important treatment strategies. Emerging evidence has shown that CSCs have a different metabolic phenotype to that of differen...
Source: BMB Reports - May 16, 2018 Category: Biochemistry Authors: Chae YC, Kim JH Tags: BMB Rep Source Type: research
Laminopathies; Mutations on single gene and various human genetic diseases.
Abstract Lamin A and its alternative splicing product Lamin C are the key intermediate filaments (IFs) of the inner nuclear membrane intermediate filament. Lamin A/C forms the inner nuclear mesh with Lamin B and works as a frame with a nuclear shape. In addition to supporting the function of nucleus, nuclear lamins perform important roles such as holding the nuclear pore complex and chromatin. However, mutations on the Lamin A or Lamin B related proteins induce various types of human genetic disorders and diseases including premature aging syndromes, muscular dystrophy, lipodystrophy and neuropathy. In this review...
Source: BMB Reports - May 16, 2018 Category: Biochemistry Authors: Kang SM, Yoon MH, Park BJ Tags: BMB Rep Source Type: research
Hindsiipropane B alleviates HIV-1 Tat-induced inflammatory responses by suppressing HDAC6-NADPH oxidase-ROS axis in astrocytes.
In this report, we explored the regulatory activity of hindsiipropane B on HIV-1 Tat-mediated chemokine production and its mode of action in astrocytes. Hindsiipropane B significantly alleviated HIV-1 Tat-mediated production of inflammatory chemokines, CCL2, CXCL8, and CXCL10. Hindsiipropane B inhibited expression of HDAC6, which is important regulator in HIV-1 Tat-mediated chemokine production. Hindsiipropane B diminished HIV-1 Tat-mediated reactive oxygen species (ROS) generation and NADPH oxidase activation/expression. Furthermore, hindsiipropane B inhibited HIV-1 Tat-mediated signaling cascades including MAPK, NF-&kapp...
Source: BMB Reports - April 27, 2018 Category: Biochemistry Authors: Jo H, Jang HY, Youn GS, Kim D, Lee CY, Jang JH, Choi SY, Jun JG, Park J Tags: BMB Rep Source Type: research
Chitinase 3-like-1, a novel regulator of Th1/CTL responses, as a therapeutic target for increasing anti-tumor immunity.
This study first suggests that Chi3l1 is a novel regulator of Th1/CTL responses and could be a target for treating cancer to increase tumor immunity. PMID: 29699605 [PubMed - as supplied by publisher] (Source: BMB Reports)
Source: BMB Reports - April 27, 2018 Category: Biochemistry Authors: Kim DH, Choi JM Tags: BMB Rep Source Type: research
Insulin Receptor Substrate 2: A Bridge between Hippo and AKT Pathways.
Abstract NAFLD induces the development of advanced liver diseases such as NASH and liver cancer. Therefore, understanding the mechanism of NAFLD development is critical for its prevention and treatment. Ablation of PTEN or Hippo pathway components induces liver cancer in a murine model by hyperactive AKT or YAP/TAZ, respectively. Although the regulation of these two pathways occurs in the same hepatocyte, the details of crosstalk between Hippo-YAP/TAZ and PTEN-AKT pathways in liver homeostasis and tumorigenesis still remain unclear. Here, we found that depletion of both PTEN and SAV1 in liver promotes spontaneous ...
Source: BMB Reports - April 27, 2018 Category: Biochemistry Authors: Jeong SH, Lim DS Tags: BMB Rep Source Type: research
Degradation or aggregation: the ramifications of post-translational modifications on tau.
Abstract Tau protein is encoded in the microtubule-associated protein tau (MAPT) gene and contributes to the stability of microtubules in axons. Despite of its basic isoelectric point and high solubility, tau is often found in intraneuronal filamentous inclusions such as paired helical filaments (PHFs), which are the primary constituent of neurofibrillary tangles (NFTs). This pathological feature is the nosological entity termed "tauopathies" which notably include Alzheimer's disease (AD). A proteinaceous signature of all tauopathies is hyperphosphorylation of the accumulated tau, which has been extensiv...
Source: BMB Reports - April 17, 2018 Category: Biochemistry Authors: Park S, Lee JH, Lee MJ Tags: BMB Rep Source Type: research
Long noncoding RNA: multiple players in gene expression.
Abstract Previously considered as a component of transcriptional noise, long noncoding RNAs ( lncRNAs) were neglected as a therapeutic target, however, recently increasing evidence has shown that lncRNAs can participate in numerous biological processes involved in genetic regulation including epigenetic, transcriptional, and post-transcriptional regulation. In this review, we discuss the fundamental functions of lncRNAs at different regulatory levels and their roles in metabolic balance. Typical examples are introduced to illustrate their diverse molecular mechanisms. The comprehensive investigation and identifica...
Source: BMB Reports - April 11, 2018 Category: Biochemistry Authors: Chen X, Sun Y, Cai R, Wang G, Shu X, Pang W Tags: BMB Rep Source Type: research
Understanding of the functional role(s) of the Activating Transcription Factor 4(ATF4) in HIV regulation and production.
Abstract The activating transcription factor (ATF) 4 belongs to the ATF/CREB (cAMP Response Element Binding bZIP (Basic Leucine Zipper)) transcription factor family, and plays a central role in the UPR (Unfolded Protein Response) process in cells. The induction of ATF4 expression has previously been shown to increase the replication of HIV-1. However, the detailed mechanism underlying this effect and the factors involved in the regulation of ATF4 function are still unknown. Here, we demonstrate first that knocking out ATF4 using siRNA shows a strong negative effect on HIV-1 production, indicating that ATF4 is a fu...
Source: BMB Reports - April 11, 2018 Category: Biochemistry Authors: Lee SD, Yu KL, Park SH, Jung YM, You JC Tags: BMB Rep Source Type: research
The role of necroptosis in the treatment of diseases.
Abstract Necroptosis is an emerging form of programmed cell death occurring via active and well-regulated necrosis, distinct from apoptosis morphologically, and biochemically. Necroptosis is mainly unmasked when apoptosis is compromised in response to cell stress. Unlike apoptotic cells, which are cleared by macrophages or neighboring cells, necrotic cells release danger signals, triggering inflammation, and exacerbating tissue damage. Evidence increasingly suggests that programmed necrosis is not only associated with pathophysiology of disease, but also induces innate immune response to viral infection. Therefore...
Source: BMB Reports - April 11, 2018 Category: Biochemistry Authors: Cho YS Tags: BMB Rep Source Type: research
Mitochondrial dysfunction suppresses p53 expression via calcium-mediated nuclear factor-kB signaling in HCT116 human colorectal carcinoma cells.
Abstract Mitochondrial DNA (mtDNA) mutations are often observed in various cancer types. Although the correlation between mitochondrial dysfunction and cancer malignancy has been demonstrated by several studies, further research is required to elucidate the molecular mechanisms underlying accelerated tumor development and progression due to mitochondrial mutations. We generated an mtDNA-depleted cell line, ρ0, via long-term ethidium bromide treatment to define the molecular mechanisms of tumor malignancy induced by mitochondrial dysfunction. Mitochondrial dysfunction in ρ0 cells reduced drug-induced cell d...
Source: BMB Reports - March 27, 2018 Category: Biochemistry Authors: Lee YK, Yi EY, Park SY, Jang WJ, Han YS, Jegal ME, Kim YJ Tags: BMB Rep Source Type: research
Photoperiod sensing system for timing of flowering in plants.
Abstract CONSTANS (CO) induces the expression of FLOWERING LOCUS T (FT) in the photoperiodic pathway, and thereby regulates the seasonal timing of flowering. CO expression is induced and CO protein is stabilized by FLAVIN-BINDING KELCH REPEAT F-BOX PROTEIN 1 (FKF1) in the late afternoon, while CO is degraded by CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1) during the night. These regulatory cascades were thought to act independently. In our study, we investigated the relationship between FKF1 and COP1 in the regulation of CO stability in response to ambient light conditions. A genetic analysis revealed that FKF1 acts as ...
Source: BMB Reports - March 27, 2018 Category: Biochemistry Authors: Lee BD, Cha JY, Kim MR, Paek NC, Kim WY Tags: BMB Rep Source Type: research
Pinosylvin exacerbates LPS-induced apoptosis via ALOX 15 upregulation in leukocytes.
In conclusion, pinosylvin enhances the apoptosis of LPS-preconditioned leukocytes by up-regulating ALOX 15 expression through ERK and JNK. These findings suggest that pinosylvin may induce the resolution of inflammation. PMID: 29555013 [PubMed - as supplied by publisher] (Source: BMB Reports)
Source: BMB Reports - March 20, 2018 Category: Biochemistry Authors: Kwon O, Seo Y, Park H Tags: BMB Rep Source Type: research
Investigation of functional roles of transcription termination factor-1 (TTF-1) in HIV-1 replication.
Abstract Transcription termination factor-1 (TTF-I) is an RNA polymerase 1-mediated transcription terminator and consisting of a C-terminal DNA-binding domain, central domain, and N-terminal regulatory domain. This protein binds to a so-called 'Sal box' composed of an 11-base pair motif. The interaction of TTF-I with the 'Sal box' is important for many cellular events, including efficient termination of RNA polymerase-1 activity involved in pre-rRNA synthesis and formation of a chromatin loop. To further understand the role of TTF-I in human immunodeficiency virus (HIV)-I virus production, we generated various TTF...
Source: BMB Reports - March 20, 2018 Category: Biochemistry Authors: Park SH, Yu KL, Jung YM, Lee SD, You JC Tags: BMB Rep Source Type: research
Inhibition of Wntless/GPR177 suppresses gastric tumorigenesis.
Abstract Wntless/GPR177 functions as WNT ligand carrier protein and activator of WNT/β-catenin signaling, however, its molecular role in gastric cancer (GC) has remained elusive. We investigated the role of GPR177 in gastric tumorigenesis and provided the therapeutic potential of a clinical development of anti-GPR177 monoclonal antibodies. GPR177 mRNA expression was assessed in GC transcriptome data sets (GSE15459, n=184; GSE66229, n=300); protein expression was assessed in independent patient tumor tissues (Yonsei TMA, n=909). GPR177 expression were associated with unfavorable prognosis [log-rank test, GSE15...
Source: BMB Reports - March 20, 2018 Category: Biochemistry Authors: Seo J, Kee HJ, Choi HJ, Lee JE, Park SY, Lee SH, Jeong MH, Guk G, Lee S, Choi KC, Choi YY, Kim H, Noh SH, Yoon HG, Cheong JH Tags: BMB Rep Source Type: research
Histone tail cleavage as a novel epigenetic regulatory mechanism for gene expression.
Abstract Chromatin is an intelligent building block that can express either external or internal needs through structural changes. To date, three methods to change chromatin structure and regulate gene expression have been well-documented: histone modification, histone exchange, and ATP-dependent chromatin remodeling. Recently, a growing body of literature has suggested that histone tail cleavage is related to various cellular processes including stem cell differentiation, osteoclast differentiation, granulocyte differentiation, mammary gland differentiation, viral infection, aging, and yeast sporulation. Although...
Source: BMB Reports - March 15, 2018 Category: Biochemistry Authors: Yi SJ, Kim K Tags: BMB Rep Source Type: research
Early Potential Effects of Resveratrol Supplementation on Skeletal Muscle Adaptation Involved in Exercise-induced Weight Loss in Obese Mice.
Abstract Exercise and resveratrol supplementation exhibit anti-obesity functions in the long term but have not been fully investigated yet in terms of their early potential effectiveness. Mice fed with high-fat diet were categorized into control (Cont), exercise (Ex), resveratrol supplementation (Res), and exercise combined with resveratrol supplementation (Ex + Res) groups. In the four-week period of weight loss, exercise combined with resveratrol supplementation exerted no additional effects on body weight loss but significantly improved whole-body glucose and lipid homeostasis. The combined treatment significan...
Source: BMB Reports - March 9, 2018 Category: Biochemistry Authors: Sun J, Zhang C, Kim M, Su Y, Qin L, Dong J, Zhou Y, Ding S Tags: BMB Rep Source Type: research
Hippo signaling: Special issue of BMB Reports in 2018.
Abstract Since the first component of Hippo signaling, Wts in Drosophila, was identified in 1995, the progress of Hippo signaling studies has been very slow initially. However, after the findings suggesting that the core kinase pathway established in Drosophila was evolutionarily conserved in metazoans for the determination of organ size around 2008, the number of publications related to Hippo signaling has grown exponentially. Identification of molecular mechanisms underlying Hippo signaling response to intrinsic cues, such as cell-cell contact and mechanotransduction, as well as extrinsic cues, such as nutrients...
Source: BMB Reports - March 9, 2018 Category: Biochemistry Authors: Jho EH Tags: BMB Rep Source Type: research
Role of estrogen and RAS signaling in repeated implantation failure.
Abstract In humans, hormonal regulation is crucial for the preparation of uterine environment leading to either successful implantation or menstrual cycle. Estrogen is a pivotal female steroid hormone that regulates the uterine dynamics along with progesterone in the estrous and menstrual cycles in humans. Estrogen signals act via nuclear estrogen receptor or membrane-bound receptor. The membrane-bound estrogen receptor plays a crucial role in the rapid response of estrogen in the uterine epithelium. Recently, RASD1 has received attention as a novel signal transducer of estrogen in various systems including female...
Source: BMB Reports - March 9, 2018 Category: Biochemistry Authors: Hong K, Choi Y Tags: BMB Rep Source Type: research
Investigation of function and regulation of the YB-1 cellular factor in HIV replication.
Abstract Y-box binding protein 1 (YB-1) is a member of the cold-shock domain (CSD) protein superfamily. It participates in a wide variety of cellular events, including transcription, RNA splicing, translation, DNA repair, drug resistance, and stress responses. We investigated putative functions of YB-1 in HIV-1 replication. Functional studies using overexpression or knockdown of YB-1 in conjunction with transfection of proviral DNA showed that YB-1 enhances virus production. We found YB-1 regulates HIV-1 production by stimulating viral transcription using HIV-1 LTR sequence U3RU5 with Luciferase assay. We identifi...
Source: BMB Reports - February 12, 2018 Category: Biochemistry Authors: Jung YM, Yu KL, Park SH, Lee SD, Kim MJ, You JC Tags: BMB Rep Source Type: research
Human amnion-derived mesenchymal stem cells induced osteogenesis and angiogenesis in human adipose-derived stem cells via ERK1/2 MAPK signaling pathway.
In this study, we investigated the effect of HAMSCs on HASCs by a transwell co-culture system. HAMSCs promoted proliferation, osteogenic differentiation, angiogenic potential and adiponectin (APN) secretion of HASCs. Moreover, the positive effect of HAMSCs was significantly inhibited by U0126, a highly selective inhibitor of extracellular signaling-regulated kinase 1/2 (ERK1/2) mitogen-activated protein kinase (MAPK) signaling pathway. These observations suggested that HAMSCs induced bone regeneration in HASCs via ERK1/2 MAPK signaling pathway. PMID: 29429450 [PubMed - as supplied by publisher] (Source: BMB Reports)
Source: BMB Reports - February 12, 2018 Category: Biochemistry Authors: Wang Y, Chen X, Yin Y, Li S Tags: BMB Rep Source Type: research
Emerging role of RUNX3 in the regulation of tumor microenvironment.
Abstract A number of genes have been therapeutically targeted to relieve cancer, but cancer relapse is still a growing issue. The concept that the surrounding tumor environment is critical for the progression of cancer may foster an answer to the issue of cancer malignancy. Runt domain transcription factors (RUNX1, 2, and 3) are evolutionarily conserved and have been intensively studied for their roles in normal development and pathological conditions. During tumor growth, a hypoxic microenvironment and infiltration of the tumor by immune cells are common phenomena. In this review, we briefly introduce the consequ...
Source: BMB Reports - February 12, 2018 Category: Biochemistry Authors: Manandhar S, Lee YM Tags: BMB Rep Source Type: research
Sex as an important biological variable in biomedical research.
Abstract Experimental results obtained from research using only one sex are sometimes extrapolated to both sexes without thorough justification. However, this might cause enormous economic loss and unintended fatalities. Between years 1997 and 2000, the US Food and Drug Administration suspended ten prescription drugs producing severe adverse effects on the market. Eight of the ten drugs caused greater health risks in women. Serious male biases in basic, preclinical, and clinical research were the main reason for the problem. This mini-review will describe why and how funding organizations such as the European Comm...
Source: BMB Reports - February 12, 2018 Category: Biochemistry Authors: Lee SK Tags: BMB Rep Source Type: research
The role of Purkinje cell-derived VEGF in cerebellar astrogliosis in Niemann-Pick type C mice.
Abstract Niemann-Pick type C disease (NP-C) is a fatal neurodegenerative disorder caused by a deficiency of NPC1 gene function, which leads to severe neuroinflammation such as astrogliosis. While reports demonstrating neuroinflammation are prevalent in NP-C, information about the onset and progression of cerebellar astrogliosis in this disorder is lacking. Using gene targeting, we generated vascular endothelial growth factor (VEGF) conditional null mutant mice. Deletion of VEGF in cerebellar Purkinje neurons (PNs) led to a significant increase of astrogliosis in the brain of NP-C mice in addition to the loss of PN...
Source: BMB Reports - February 5, 2018 Category: Biochemistry Authors: Park MH, Lee JY, Jeong MS, Jang HS, Endo S, Bae JS, Jin HK Tags: BMB Rep Source Type: research
Drug resistance of bladder cancer cells through activation of ABCG2 by FOXM1.
Abstract Recurrence is a serious problem in patients with bladder cancer. The hypothesis for recurrence was that the proliferation of drug-resistant cells was reported, and this study focused on drug resistance due to drug efflux. Previous studies have identified FOXM1 as the key gene for recurrence. We found that FOXM1 inhibition decreased drug efflux activity and increased sensitivity to Doxorubicin. Therefore, we examined whether the expression of ABC transporter gene related to drug efflux is regulated by FOXM1. As a result, ABCG2, one of the genes involved in drug efflux, has been identified as a new target f...
Source: BMB Reports - February 5, 2018 Category: Biochemistry Authors: Roh YG, Mun MH, Jeong MS, Kim WT, Lee SR, Chung JW, Kim SI, Kim TN, Nam JK, Leem SH Tags: BMB Rep Source Type: research
Structure and function of vascular endothelial growth factor and its receptor system.
Abstract Vascular endothelial growth factor and its receptor (VEGF-VEGFR) system play a critical role in the regulation of angiogenesis and lymphangiogenesis in vertebrates. Each of the VEGF has specific receptors, which it activates by binding to the extracellular domain of the receptors, and, thus, regulates the angiogenic balance in the early embryonic and adult stages. However, de-regulation of the VEGF-VEGFR implicates directly in various diseases, particularly cancer. Moreover, tumor growth needs a dedicated blood supply to provide oxygen and other essential nutrients. Tumor metastasis requires blood vessels...
Source: BMB Reports - February 5, 2018 Category: Biochemistry Authors: Park SA, Jeong MS, Ha KT, Jang SB Tags: BMB Rep Source Type: research
SF3B4 as an early-stage diagnostic marker and driver of hepatocellular carcinoma.
Abstract An accurate diagnostic marker for detecting early-stage hepatocellular carcinoma (eHCC) is clinically important, since early detection of HCC remarkably improves patient survival. From the integrative analysis of the transcriptome and clinicopathologic data of human multi-stage HCC tissues, we were able to identify barrier-to-autointegration factor 1 (BANF1), procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3 (PLOD3) and splicing factor 3b subunit 4 (SF3B4) as early HCC biomarkers which could be detected in precancerous lesions of HCC, with superior capabilities to diagnose eHCC compared to the currently ...
Source: BMB Reports - February 5, 2018 Category: Biochemistry Authors: Shen Q, Nam SW Tags: BMB Rep Source Type: research
The history and regulatory mechanism of the Hippo pathway.
Abstract How the organ size is adjusted to the proper size during development and how organs know that they reach the original size during regeneration remain long-standing questions. Based on studies using multiple model organisms and approaches for over 20 years, a consensus has been established that the Hippo pathway plays crucial roles in controlling organ size and maintaining tissue homeostasis. Given the significance of these processes, the dysregulation of the Hippo pathway has also implicated various diseases, such as tissue degeneration and cancer. By regulating the downstream transcriptional coactivators...
Source: BMB Reports - February 5, 2018 Category: Biochemistry Authors: Kim W, Jho EH Tags: BMB Rep Source Type: research
Upstream paths for Hippo signaling in Drosophila organ development.
Abstract Organ growth is fundamental to animal development. One of major mechanisms for growth control is mediated by the conserved Hippo signaling pathway initially identified in Drosophila. The core of this pathway in Drosophila consists of a cascade of protein kinases Hippo and Warts that negatively regulate transcriptional coactivator Yorkie (Yki). Activation of Yki promotes cell survival and proliferation to induce organ growth. A key issue in Hippo signaling is to understand how core kinase cascade is activated. Activation of Hippo kinase cascade is regulated in the upstream by at least two transmembrane pro...
Source: BMB Reports - February 5, 2018 Category: Biochemistry Authors: Choi KW Tags: BMB Rep Source Type: research
Oxygen Matters: Hypoxia as a Pathogenic Mechanism in Rhinosinusitis.
Abstract The airway epithelium is the first place, where a defense mechanism is initiated against environmental stimuli. Mucociliary transport (MCT), which is the defense mechanism of the airway and the role of airway epithelium as mechanical barriers are essential in innate immunity. To maintain normal physiologic function, normal oxygenation is critical for the production of energy for optimal cellular functions. Several pathologic conditions are associated with a decrease in oxygen tension in airway epithelium and chronic sinusitis is one of the airway diseases, which is associated with the hypoxic condition, a...
Source: BMB Reports - January 25, 2018 Category: Biochemistry Authors: Cho HJ, Kim CH Tags: BMB Rep Source Type: research
DNA binding partners of YAP/TAZ.
Abstract Hippo signaling plays critical roles in regulation of tissue homeostasis, organ size, and tumorigenesis by inhibiting YES-associated protein (YAP) and PDZ-binding protein TAZ through MST1/2 and LATS1/2 pathway. It is also engaged in cross-talk with various other signaling pathways, including WNT, BMPs, Notch, GPCRs, and Hedgehog to further modulate activities of YAP/TAZ. Because YAP and TAZ are transcriptional coactivators that lack DNA-binding activity, both proteins must interact with DNA-binding transcription factors to regulate target gene's expression. To activate target genes involved in cell prolif...
Source: BMB Reports - January 25, 2018 Category: Biochemistry Authors: Kim MK, Jang JW, Bae SC Tags: BMB Rep Source Type: research
Hippo-YAP/TAZ Signaling in Angiogenesis.
Abstract Angiogenesis is a complex, multistep process involving dynamic changes in endothelial cell (EC) shapes and behaviors, especially in specialized cell types such as tip cells (with active filopodial extensions), stalk cells (with less motility) and phalanx cells (with stable junction connections). The Hippo-Yes-associated protein (YAP)/ transcription activator with PDZ binding motif (TAZ) signaling plays a critical role in development, regeneration and organ size by regulating cell-cell contact and actin cytoskeleton dynamics. Recently, with the finding that YAP is expressed in the front edge of the develop...
Source: BMB Reports - January 25, 2018 Category: Biochemistry Authors: Park JA, Kwon YG Tags: BMB Rep Source Type: research
Regulation of the Hippo Signaling Pathway by Ubiquitin Modification.
Abstract The Hippo signaling pathway plays an essential role in adult tissue homeostasis and organ size control. Abnormal regulation of Hippo signaling can be a cause for multiple types of human cancers. Since the awareness of the importance of the Hippo signaling in a wide range of biological fields has been continually grown, it is also understood that a thorough and well-rounded comprehension of the precise dynamics could provide fundamental insights for therapeutic applications. Several components in the Hippo signaling pathway are known to be targeted for proteasomal degradation via ubiquitination by E3 ligas...
Source: BMB Reports - January 25, 2018 Category: Biochemistry Authors: Kim Y, Jho EH Tags: BMB Rep Source Type: research
Clinical Implications of the Hippo-YAP Pathway in Multiple Cancer Contexts.
Abstract The Hippo pathway plays prominent and widespread roles in various forms of human carcinogenesis. Specifically, the Yes-associated protein (YAP), a downstream effector of the Hippo pathway, can lead to excessive cell proliferation and the inhibition of apoptosis, resulting in tumorigenesis. It was reported that the YAP is strongly elevated in multiple types of human malignancies such as breast, lung, small intestine, colon, and liver cancers. Recent work indicates that, surprisingly, Hippo signaling components' (SAV1, MST1/2, Lats1/2) mutations are virtually absent in human cancer, rendering this signaling...
Source: BMB Reports - January 25, 2018 Category: Biochemistry Authors: Kim HB, Myung SJ Tags: BMB Rep Source Type: research
Estrogen-related receptor γ is a novel catabolic regulator of osteoarthritis pathogenesis.
Estrogen-related receptor γ is a novel catabolic regulator of osteoarthritis pathogenesis. BMB Rep. 2018 Jan 25;: Authors: Son YO, Chun JS Abstract Osteoarthritis (OA) is the most common form of arthritis and is a leading cause of disability with a large socioeconomic cost. OA is a whole-joint disease characterized by cartilage destruction, synovial inflammation, osteophyte formation, and subchondral bone sclerosis. To date, however, no effective disease-modifying therapies for OA have been developed. The estrogen-related receptors (ERRs), a family of orphan nuclear receptor transcription factor...
Source: BMB Reports - January 25, 2018 Category: Biochemistry Authors: Son YO, Chun JS Tags: BMB Rep Source Type: research
Medicarpin induces lipolysis via activation of Protein Kinase A in brown adipocytes.
Abstract Natural pterocarpan Medicarpin (Med) has been shown to have various beneficial biological roles, including inhibition of osteoclastogenesis, stimulation of bone regeneration and induction of apoptosis. However, the effect of the Med on lipolysis in adipocytes has not been reported. Here, we show the effect of Med on lipolysis in different mouse adipocytes and elucidate the underlying mechanism. We observed that Med treatment promoted release of glycerol in the media. Differentiated mouse brown adipose tissue cells were treated with Med. RNA-Seq analysis was performed to elucidate the effect of med and sub...
Source: BMB Reports - January 22, 2018 Category: Biochemistry Authors: Imran KM, Yoon D, Lee TJ, Kim YS Tags: BMB Rep Source Type: research
New Role of LTR-Retrotransposons for Emergence and Expansion of Disease-Resistance Genes and High-Copy Gene Families in Plants.
In this study, we constructed new reference genome sequences of two pepper species (Capsicum baccatum and C. chinense), and updated the reference genome of C. annuum. We focused on the study for speciation of Capsicum spp. and its driving forces. We found that chromosomal translocation, unequal amplification of LTR-Rs, and recent gene duplications in the pepper genomes as major evolutionary forces for diversification of Capsicum spp. Specifically, our analyses revealed that the nucleotide-binding and leucine-rich-repeat proteins (NLRs) were massively created by LTR-R-driven retroduplication. These retoduplicated NLRs were ...
Source: BMB Reports - January 22, 2018 Category: Biochemistry Authors: Kim S, Choi D Tags: BMB Rep Source Type: research
MicroRNAs as Critical Regulators of the Endothelial to Mesenchymal Transition in Vascular Biology.
Abstract The endothelial to mesenchymal transition (EndMT) is a newly recognized, fundamental biological process involved in development and tissue regeneration, as well as pathological processes such as the complications of diabetes, fibrosis and pulmonary arterial hypertension. The EndMT process is tightly controlled by diverse signaling networks, similar to the epithelial to mesenchymal transition. Accumulating evidence suggests that microRNAs (miRNAs) are key regulators of this network, with the capacity to target multiple messenger RNAs involved in the EndMT process as well as in the regulation of disease pro...
Source: BMB Reports - January 22, 2018 Category: Biochemistry Authors: Kim J Tags: BMB Rep Source Type: research
Regulation of Hippo Signaling by Actin Remodeling.
Abstract The Hippo signaling pathway controls nuclear accumulation and stability of the transcriptional coregulator YAP and its paralog TAZ. The activity of Hippo-YAP signaling is influenced not only by biochemical signals, but also by cell shape and mechanical tension transmitted through cell-cell junctions and cell-matrix adhesions. Data accumulated thus far indicates that the actin cytoskeleton is a key mediator of the regulation of Hippo-YAP signaling by means of a variety of biochemical and mechanical cues. In this review, we have outlined the role of actin dynamics and actin-associated proteins in the regula...
Source: BMB Reports - January 22, 2018 Category: Biochemistry Authors: Seo J, Kim J Tags: BMB Rep Source Type: research
Gata6 in pluripotent stem cells enhance the potential to differentiate into cardiomyocytes.
In conclusion, Gata6 could be utilized as a biomarker to select the best PSC lines to produce PSC-derived cardiomyocytes for therapeutic purposes. PMID: 29335067 [PubMed - as supplied by publisher] (Source: BMB Reports)
Source: BMB Reports - January 16, 2018 Category: Biochemistry Authors: Yoon CH, Kim TW, Koh SJ, Choi YE, Hur J, Kwon YW, Cho HJ, Kim HS Tags: BMB Rep Source Type: research
Imprinted gene Zinc finger protein 127 is a novel regulator of master pluripotency transcription factor, Oct4.
Abstract Induced pluripotent stem cells (iPSCs) show great promise for replacing current stem cell therapies in the field of regenerative medicine. However, the original method for cellular reprogramming, involving four exogenous transcription factors, is characterized by low efficiency. Here, we focused on using epigenetic modifications to enhance the reprogramming efficiency. We hypothesized that there would be a new reprogramming factor involved in DNA demethylation, acting on the promoters of pluripotency-related genes. We screened proteins that bind to the methylated promoter of Oct4 and identified Zinc finge...
Source: BMB Reports - January 16, 2018 Category: Biochemistry Authors: Kwon YW, Ahn HS, Park JY, Yang HM, Cho HJ, Kim HS Tags: BMB Rep Source Type: research
Functional roles of glutamic acid E143 and E705 residues in the N-terminus and transmembrane domain 7 of Anoctamin 1 in calcium and noxious heat sensing.
Abstract Anoctamin 1 (ANO1) is an anion channel that is activated by changes in cytosolic Ca2+ concentration and noxious heat. Although the critical roles of ANO1 have been elucidated in various cell types, the control of its gating mechanisms by Ca2+ and heat remain more elusive. To investigate critical amino acid residues for modulation of Ca2+ and heat sensing, we constructed a randomized mutant library for ANO1. Among 695 random mutants, reduced Ca2+ sensitivity was observed in two mutants (mutant 84 and 87). Consequently, the E143A mutant showed reduced sensitivity to Ca2+ but not to high temperatures, wherea...
Source: BMB Reports - January 16, 2018 Category: Biochemistry Authors: Choi J, Jang Y, Kim H, Wee J, Cho S, Son WS, Kim SM, Yang YD Tags: BMB Rep Source Type: research
Cell Proliferation and Migration Mechanism of Caffeoylserotonin and Serotonin via Serotonin 2B receptor in Human Keratinocyte HaCaT cells.
In this study, we investigated the effect of CaS on proliferation and migration of human keratinocyte HaCaT cells compared to that of 5-HT. CaS enhanced keratinocyte proliferation even under serum deficient condition. This effect of CaS was mediated by serotonin 2B receptor (5-HT2BR) related to the cell proliferation effect of 5-HT. We also confirmed that both CaS and 5-HT induced G1 progression via 5-HT2BR/ERK pathway in HaCaT cells. However, Akt pathway was additionally involved in upregulated expression levels of cyclin D1 and cyclin E induced by CaS by activating 5-HT2BR. Moreover, CaS and 5-HT induced cell migration i...
Source: BMB Reports - January 16, 2018 Category: Biochemistry Authors: Kim HE, Cho H, Ishihara A, Kim B, Kim O Tags: BMB Rep Source Type: research
Adequate concentration of B cell leukemia/lymphoma 3 (Bcl3) is required for pluripotency and self-renewal of mouse embryonic stem cells via downregulation of Nanog transcription.
In conclusion, we demonstrated that a sufficient concentration of Bcl3 in mESCs plays a critical role in the maintenance of pluripotency and the self-renewal of mESCs via the regulation of Nanog transcriptional activity. PMID: 29335071 [PubMed - as supplied by publisher] (Source: BMB Reports)
Source: BMB Reports - January 16, 2018 Category: Biochemistry Authors: Kang S, Yun J, Kim DY, Jung SY, Kim YJ, Park JH, Ji ST, Jang WB, Ha J, Kim JH, Baek SH, Kwon SM Tags: BMB Rep Source Type: research