Biochemistry, Biophysics, and Structural Biology Commons^™

Presence Of A Prophage Determines Temperature-Dependent Capsule Production In Streptococcus Pyogenes., Leslie Brown, Jeong-Ho Kim, Kyu Hong Cho

Biochemistry and Molecular Medicine Faculty Publications

A hyaluronic acid capsule is a major virulence factor in the pathogenesis of Streptococcus pyogenes. It acts as an anti-phagocytic agent and adhesin to keratinocytes. The expression of the capsule is primarily regulated at the transcriptional level by the two-component regulatory system CovRS, in which CovR acts as a transcriptional repressor. The covRS genes are frequently mutated in many invasive strains, and a subset of the invasive CovRS mutants does not produce a detectable level of the capsule at 37 °C, but produces a significant amount of the capsule at sub-body temperatures. Here, we report that a prophage has a …

Rna2dnalign: Nucleotide Resolution Allele Asymmetries Through Quantitative Assessment Of Rna And Dna Paired Sequencing Data., Mercedeh Movassagh, Nawaf Alomran, Prakriti Mudvari, Merve Dede, Cem Dede, Kamran Kowsari, Paula Restrepo, Edmund Cauley, Sonali Bahl, Muzi Li, Wesley Waterhouse, Krasimira Tsaneva-Atanasova, Nathan Edwards, Anelia Horvath

Biochemistry and Molecular Medicine Faculty Publications

We introduce RNA2DNAlign, a computational framework for quantitative assessment of allele counts across paired RNA and DNA sequencing datasets. RNA2DNAlign is based on quantitation of the relative abundance of variant and reference read counts, followed by binomial tests for genotype and allelic status at SNV positions between compatible sequences. RNA2DNAlign detects positions with differential allele distribution, suggesting asymmetries due to regulatory/structural events. Based on the type of asymmetry, RNA2DNAlign outlines positions likely to be implicated in RNA editing, allele-specific expression or loss, somatic mutagenesis or loss-of-heterozygosity (the first three also in a tumor-specific setting). We applied RNA2DNAlign on 360 matching …

Inhibition Of Nuclear Factor-Kappa B Enhances The Tumor Growth Of Ovarian Cancer Cell Line Derived From A Low-Grade Papillary Serous Carcinoma In P53-Independent Pathway, Xue Xiao, Gong Yang, Peng Bai, Shunping Gui, Tri M. Bui Nguyen, +8 Additional Authors

Biochemistry and Molecular Medicine Faculty Publications

Background: NF-kB can function as an oncogene or tumor suppressor depending on cancer types. The role of NF-kB in low-grade serous ovarian cancer, however, has never been tested. We sought to elucidate the function of NF-kB in the low-grade serous ovarian cancer.

Methods: The ovarian cancer cell line, HOC-7, derived from a low-grade papillary serous carcinoma. Introduction of a dominant negative mutant, IkBαM, which resulted in decrease of NF-kB function in ovarian cancer cell lines. The transcription ability, tumorigenesis, cell proliferation and apoptosis were observed in derivative cell lines in comparison with parental cells.

Results: Western blot analysis indicated increased …

Mof Acetylates The Histone Demethylase Lsd1 To Suppress Epithelial-To-Mesenchymal Transition., Huacheng Luo, Anitha K Shenoy, Xuehui Li, Yue Jin, Lihua Jin, Edward Seto, +10 Additional Authors

Biochemistry and Molecular Medicine Faculty Publications

The histone demethylase LSD1 facilitates epithelial-to-mesenchymal transition (EMT) and tumor progression by repressing epithelial marker expression. However, little is known about how its function may be modulated. Here, we report that LSD1 is acetylated in epithelial but not mesenchymal cells. Acetylation of LSD1 reduces its association with nucleosomes, thus increasing histone H3K4 methylation at its target genes and activating transcription. The MOF acetyltransferase interacts with LSD1 and is responsible for its acetylation. MOF is preferentially expressed in epithelial cells and is downregulated by EMT-inducing signals. Expression of exogenous MOF impedes LSD1 binding to epithelial gene promoters and histone demethylation, thereby …

Identification Of Genes That Are Essential To Restrict Genome Duplication To Once Per Cell Division., Alex Vassilev, Chrissie Y. Lee, Boris Vassilev, Wenge Zhu, Pinar Ormanoglu, Scott E. Martin, Melvin L. Depamphilis

Biochemistry and Molecular Medicine Faculty Publications

Nuclear genome duplication is normally restricted to once per cell division, but aberrant events that allow excess DNA replication (EDR) promote genomic instability and aneuploidy, both of which are characteristics of cancer development. Here we provide the first comprehensive identification of genes that are essential to restrict genome duplication to once per cell division. An siRNA library of 21,584 human genes was screened for those that prevent EDR in cancer cells with undetectable chromosomal instability. Candidates were validated by testing multiple siRNAs and chemical inhibitors on both TP53+ and TP53- cells to reveal the relevance of this ubiquitous tumor suppressor …

Stabilizing The Cold Plasma-Stimulated Medium By Regulating Medium’S Composition, Dayun Yan, Niki Nourmohammadi, Ka Bian, Ferid Murad, Jonathan H. Sherman, Michael Keidar

Biochemistry and Molecular Medicine Faculty Publications

Over past several years, the cold plasma-stimulated medium (PSM) has shown its remarkable anti-cancer capacity in par with the direct cold plasma irradiation on cancer cells or tumor tissues. Independent of the cold plasma device, PSM has noticeable advantage of being a flexible platform in cancer treatment. Currently, the largest disadvantage of PSM is its degradation during the storage over a wide temperature range. So far, to stabilize PSM, it must be remained frozen at −80 °C. In this study, we first reveal that the degradation of PSM is mainly due to the reaction between the reactive species and specific …

Oxidative Stress, Cellular Senescence And Ageing, Akshaj Pole, Manjari Dimri, Goberdhan P. Dimri

Biochemistry and Molecular Medicine Faculty Publications

Almost a half century ago, the free radical theory of ageing proposed that the reactive oxygen species (ROS) is a key component which contributes to the pathophysiology of ageing in mammalian cells. Over the years, numerous studies have documented the role of oxidative stress caused by ROS in the ageing process of higher organisms. In particular, several age-associated disease models suggest that ROS and oxidative stress modulate the incidence of age-related pathologies, and that it can strongly influence the ageing process and possibly lifespan. The exact mechanism of ROS and oxidative stress-induced age-related pathologies is not yet very clear. Damage …

A Mir-200c/141-Bmi1 Autoregulatory Loop Regulates Oncogenic Activity Of Bmi1 In Cancer Cells., Mingu Kang, Manjari Dimri, Goberdhan P. Dimri

Biochemistry and Molecular Medicine Faculty Publications

MicroRNAs (miRNAs) are known to function as oncomiRs or tumor suppressors and are important noncoding RNA regulators of oncogenesis. The miR-200c/141 locus on chromosome 12 encodes miR-200c and miR-141, two members of the miR-200 family, which have been shown to function as tumor suppressive miRNAs by targeting multiple oncogenic factors such as polycomb group protein BMI1. Here, we show that BMI1 reciprocally functions as a transcriptional repressor of the miR-200c/141 cluster and that BMI1 inhibitors upregulate expression of miR-200c and miR-141. Our data suggest that BMI1 binds to the miR-200c/141 promoter and regulates it through transcription factor binding motifs E-box …

The Glucose Metabolite Methylglyoxal Inhibits Expression Of The Glucose Transport Genes By Inactivating The Cell Surface Glucose Sensors Rgt2 And Snf3 In Yeast, Adhiraj Roy, Salman Hashmi, Zerui Li, Angela Dement, Kyu Hong Cho, Jeong-Ho Kim

Biochemistry and Molecular Medicine Faculty Publications

Methylglyoxal (MG) is a cytotoxic by-product of glycolysis. MG has inhibitory effect on the growth of cells ranging from microorganisms to higher eukaryotes, but its molecular targets are largely unknown. The yeast cell-surface glucose sensors Rgt2 and Snf3 function as glucose receptors that sense extracellular glucose and generate a signal for induction of expression of genes encoding glucose transporters (HXTs). Here we provide evidence that these glucose sensors are primary targets of MG in yeast. MG inhibits the growth of glucose-fermenting yeast cells by inducing endocytosis and degradation of the glucose sensors. However, the glucose sensors with mutations …

Distinct Lymphocyte Antigens 6 (Ly6) Family Members Ly6d, Ly6e, Ly6k And Ly6h Drive Tumorigenesis And Clinical Outcome., Linlin Luo, Peter Mcgarvey, Subha Madhavan, Rakesh Kumar, Yuriy Gusev, Geeta Upadhyay

Biochemistry and Molecular Medicine Faculty Publications

Stem cell antigen-1 (Sca-1) is used to isolate and characterize tumor initiating cell populations from tumors of various murine models [1]. Sca-1 induced disruption of TGF-β signaling is required in vivo tumorigenesis in breast cancer models [2, 3-5]. The role of human Ly6 gene family is only beginning to be appreciated in recent literature [6-9]. To study the significance of Ly6 gene family members, we have visualized one hundred thirty gene expression omnibus (GEO) dataset using Oncomine (Invitrogen) and Georgetown Database of Cancer (G-DOC). This analysis showed that four different members Ly6D, Ly6E, Ly6H or Ly6K have increased gene expressed …

Impact Of Germline And Somatic Missense Variations On Drug Binding Sites., C Yan, N Pattabiraman, J Goecks, P Lam, A Nayak, Y Pan, J Torcivia-Rodriguez, A Voskanian, Q Wan, Raja Mazumder

Biochemistry and Molecular Medicine Faculty Publications

Advancements in next-generation sequencing (NGS) technologies are generating a vast amount of data. This exacerbates the current challenge of translating NGS data into actionable clinical interpretations. We have comprehensively combined germline and somatic nonsynonymous single-nucleotide variations (nsSNVs) that affect drug binding sites in order to investigate their prevalence. The integrated data thus generated in conjunction with exome or whole-genome sequencing can be used to identify patients who may not respond to a specific drug because of alterations in drug binding efficacy due to nsSNVs in the target protein's gene. To identify the nsSNVs that may affect drug binding, protein-drug complex …

Cancer Genomics And Biology 2015 – Meeting Report, Louis W.C. Chow, Luis Costa, Bin-Tean Teh, Da-Qiang Li, Gu Feng, Rakesh Kumar, +10 Additional Authors

Biochemistry and Molecular Medicine Faculty Publications

The Cancer Genomics and Biology 2015 meeting embodied a three way collaboration among colleagues from the Global Cancer Genomics Consortium (GCGC), the Unifaith Cancer Institute China and Jiujiang University of China. The meeting marks the fifth and the last meeting of GCGC, which was formed in 2010. Previous four GCGC meetings have been held at the Tata Memorial Center- Mumbai, Institute of Molecular Medicine-Lisbon, and Graduate Medical School Kyoto University-Kyoto. In contrast to the genomic themes of the previous meetings, the 2015 conference theme was at the interface of laboratory and translation research and emerging therapeutics as reflected in the …

Potential Role Of P21 Activated Kinase 1 (Pak1) In The Invasion And Motility Of Oral Cancer Cells., Muraleedharan Parvathy, Sreeharshan Sreeja, Rakesh Kumar, M. Radhakrishna Pillai

Biochemistry and Molecular Medicine Faculty Publications

Background

Oral cancer malignancy consists of uncontrolled division of cells primarily in and around the floor of the oral cavity, gingiva, oropharynx, lower lip and base of the tongue. According to GLOBOCAN 2012 report, oral cancer is one of the most common cancers among males and females in India. Even though significant advancements have been made in the field of oral cancer treatment modalities, the overall prognosis for the patients has not improved in the past few decades and hence, this demands a new thrust for the identification of novel therapeutic targets in oral cancer. p21 Activated Kinases (PAKs) are …

And-1 Is Required For Homologous Recombination Repair By Regulating Dna End Resection, Yongming Li, Zongzhu Li, Zhiyong Han, Wenge Zhu

Biochemistry and Molecular Medicine Faculty Publications

Homologous recombination (HR) is a major mechanism to repair DNA double-strand breaks (DSBs). Although tumor suppressor CtIP is critical for DSB end resection, a key initial event of HR repair, the mechanism regulating the recruitment of CtIP to DSB sites remains largely unknown. Here, we show that acidic nucleoplasmic DNA‐binding protein 1 (And‐1) forms complexes with CtIP as well as other repair proteins, and is essential for HR repair by regulating DSB end resection. Furthermore, And-1 is recruited to DNA DSB sites in a manner dependent on MDC1, BRCA1 and ATM, down-regulation of And-1 impairs end resection by reducing the …

Low-Ω3 Fatty Acid And Soy Protein Attenuate Alcohol-Induced Fatty Liver And Injury By Regulating The Opposing Lipid Oxidation And Lipogenic Signaling Pathways., Karina Reyes-Gordillo, Ruchi Shah, Ravi Varatharajalu, Mamatha Garige, Leslie C. Leckey, M. Raj Lakshman

Biochemistry and Molecular Medicine Faculty Publications

Chronic ethanol-induced downregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) and upregulation of peroxisome proliferator-activated receptor gamma coactivator 1-beta (PGC1β) affect hepatic lipid oxidation and lipogenesis, respectively, leading to fatty liver injury. Low-ω3 fatty acid (Low-ω3FA) that primarily regulates PGC1α and soy protein (SP) that seems to have its major regulatory effect on PGC1β were evaluated for their protective effects against ethanol-induced hepatosteatosis in rats fed with Lieber-deCarli control or ethanol liquid diets with high or low ω3FA fish oil and soy protein. Low-ω3FA and SP opposed the actions of chronic ethanol by reducing serum and liver lipids with …

Protective Role Of Dietary Curcumin In The Prevention Of The Oxidative Stress Induced By Chronic Alcohol With Respect To Hepatic Injury And Antiatherogenic Markers, Ravi Varatharajalu, Mamatha Garige, Leslie C Leckey, Karina Reyes-Gordillo, Ruchi Shah, M. Raj Lakshman

Biochemistry and Molecular Medicine Faculty Publications

No abstract provided.

Dimex: A Text Mining System For Mutation-Disease Association Extraction., A S M Ashique Mahmood, Tsung-Jung Wu, Raja Mazumder, K Vijay-Shanker

Biochemistry and Molecular Medicine Faculty Publications

The number of published articles describing associations between mutations and diseases is increasing at a fast pace. There is a pressing need to gather such mutation-disease associations into public knowledge bases, but manual curation slows down the growth of such databases. We have addressed this problem by developing a text-mining system (DiMeX) to extract mutation to disease associations from publication abstracts. DiMeX consists of a series of natural language processing modules that preprocess input text and apply syntactic and semantic patterns to extract mutation-disease associations. DiMeX achieves high precision and recall with F-scores of 0.88, 0.91 and 0.89 when evaluated …