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Articles 1 - 30 of 81
Full-Text Articles in Life Sciences
Advances In Gene Ontology Utilization Improve Statistical Power Of Annotation Enrichment, Eugene Waverly Hinderer Iii, Robert M. Flight, Rashmi Dubey, James N. Macleod, Hunter N. B. Moseley
Advances In Gene Ontology Utilization Improve Statistical Power Of Annotation Enrichment, Eugene Waverly Hinderer Iii, Robert M. Flight, Rashmi Dubey, James N. Macleod, Hunter N. B. Moseley
Maxwell H. Gluck Equine Research Center Faculty Publications
Gene-annotation enrichment is a common method for utilizing ontology-based annotations in gene and gene-product centric knowledgebases. Effective utilization of these annotations requires inferring semantic linkages by tracing paths through edges in the ontological graph, referred to as relations. However, some relations are semantically problematic with respect to scope, necessitating their omission or modification lest erroneous term mappings occur. To address these issues, we created the Gene Ontology Categorization Suite, or GOcats—a novel tool that organizes the Gene Ontology into subgraphs representing user-defined concepts, while ensuring that all appropriate relations are congruent with respect to scoping semantics. Here, we demonstrate the …
Transcriptional Regulation Factors Of The Human Mitochondrial Aspartate/Glutamate Carrier Gene, Isoform 2 (Slc25a13): Usf1 As Basal Factor And Foxa2 As Activator In Liver Cells, Paolo Convertini, Simona Todisco, Francesco De Santis, Ilaria Pappalardo, Dominga Iacobazzi, Maria Antonietta Castiglione Morelli, Yvonne N. Fondufe-Mittendorf, Giuseppe Martelli, Ferdinando Palmieri, Vittoria Infantino
Transcriptional Regulation Factors Of The Human Mitochondrial Aspartate/Glutamate Carrier Gene, Isoform 2 (Slc25a13): Usf1 As Basal Factor And Foxa2 As Activator In Liver Cells, Paolo Convertini, Simona Todisco, Francesco De Santis, Ilaria Pappalardo, Dominga Iacobazzi, Maria Antonietta Castiglione Morelli, Yvonne N. Fondufe-Mittendorf, Giuseppe Martelli, Ferdinando Palmieri, Vittoria Infantino
Molecular and Cellular Biochemistry Faculty Publications
Mitochondrial carriers catalyse the translocation of numerous metabolites across the inner mitochondrial membrane, playing a key role in different cell functions. For this reason, mitochondrial carrier gene expression needs tight regulation. The human SLC25A13 gene, encoding for the mitochondrial aspartate/glutamate carrier isoform 2 (AGC2), catalyses the electrogenic exchange of aspartate for glutamate plus a proton, thus taking part in many metabolic processes including the malate-aspartate shuttle. By the luciferase (LUC) activity of promoter deletion constructs we identified the putative promoter region, comprising the proximal promoter (−442 bp/−19 bp), as well as an enhancer region (−968 bp/−768 bp). Furthermore, with different …
Stress-Induced Epinephrine Enhances Lactate Dehydrogenase A And Promotes Breast Cancer Stem-Like Cells, Bai Cui, Yuanyuan Luo, Pengfei Tian, Fei Peng, Jinxin Lu, Yongliang Yang, Qitong Su, Bing Liu, Jiachuan Yu, Xi Luo, Liu Yin, Wei Cheng, Fan An, Bin He, Dapeng Liang, Sijin Wu, Peng Chu, Luyao Song, Xinyu Liu, Huandong Luo, Binhua P. Zhou
Stress-Induced Epinephrine Enhances Lactate Dehydrogenase A And Promotes Breast Cancer Stem-Like Cells, Bai Cui, Yuanyuan Luo, Pengfei Tian, Fei Peng, Jinxin Lu, Yongliang Yang, Qitong Su, Bing Liu, Jiachuan Yu, Xi Luo, Liu Yin, Wei Cheng, Fan An, Bin He, Dapeng Liang, Sijin Wu, Peng Chu, Luyao Song, Xinyu Liu, Huandong Luo, Binhua P. Zhou
Molecular and Cellular Biochemistry Faculty Publications
Chronic stress triggers activation of the sympathetic nervous system and drives malignancy. Using an immunodeficient murine system, we showed that chronic stress–induced epinephrine promoted breast cancer stem-like properties via lactate dehydrogenase A–dependent (LDHA-dependent) metabolic rewiring. Chronic stress–induced epinephrine activated LDHA to generate lactate, and the adjusted pH directed USP28-mediated deubiquitination and stabilization of MYC. The SLUG promoter was then activated by MYC, which promoted development of breast cancer stem-like traits. Using a drug screen that targeted LDHA, we found that a chronic stress–induced cancer stem-like phenotype could be reversed by vitamin C. These findings demonstrated the critical importance of psychological …
Immunization Of Alpacas (Lama Pacos) With Protein Antigens And Production Of Antigen-Specific Single Domain Antibodies, K. Martin Chow, Sidney W. Whiteheart, Jeffrey R. Smiley, Savita Sharma, Kathy Boaz, Meggie J. Coleman, Alvina Maynard, Louis B. Hersh, Craig W. Vander Kooi
Immunization Of Alpacas (Lama Pacos) With Protein Antigens And Production Of Antigen-Specific Single Domain Antibodies, K. Martin Chow, Sidney W. Whiteheart, Jeffrey R. Smiley, Savita Sharma, Kathy Boaz, Meggie J. Coleman, Alvina Maynard, Louis B. Hersh, Craig W. Vander Kooi
Molecular and Cellular Biochemistry Faculty Publications
In this manuscript, a method for the immunization of alpaca and the use of molecular biology methods to produce antigen-specific single domain antibodies is described and demonstrated. Camelids, such as alpacas and llamas, have become a valuable resource for biomedical research since they produce a novel type of heavy chain-only antibody which can be used to produce single domain antibodies. Because the immune system is highly flexible, single domain antibodies can be made to many different protein antigens, and even different conformations of the antigen, with a very high degree of specificity. These features, among others, make single domain antibodies …
Antisense Oligonucleotides Targeting Angiotensinogen: Insights From Animal Studies, Chia-Hua Wu, Ya Wang, Murong Ma, Adam E. Mullick, Rosanne M. Crooke, Mark J. Graham, Alan Daugherty, Hong S. Lu
Antisense Oligonucleotides Targeting Angiotensinogen: Insights From Animal Studies, Chia-Hua Wu, Ya Wang, Murong Ma, Adam E. Mullick, Rosanne M. Crooke, Mark J. Graham, Alan Daugherty, Hong S. Lu
Saha Cardiovascular Research Center Faculty Publications
Angiotensinogen (AGT) is the unique substrate of all angiotensin peptides. We review the recent preclinical research of AGT antisense oligonucleotides (ASOs), a rapidly evolving therapeutic approach. The scope of the research findings not only opens doors for potentially new therapeutics of hypertension and many other diseases, but also provides insights into understanding critical physiological and pathophysiological roles mediated by AGT.
Targeting The Brd4/Foxo3a/Cdk6 Axis Sensitizes Akt Inhibition In Luminal Breast Cancer, Jingyi Liu, Weijie Guo, Zhibing Duan, Lei Zeng, Yadi Wu, Yule Chen, Fang Tai, Yifan Wang, Yiwei Lin, Qiang Zhang, Yanling He, Jiong Deng, Rachel L. Stewart, Chi Wang, Pengnian Charles Lin, Saghi Ghaffari, B. Mark Evers, Suling Liu, Ming-Ming Zhou, Binhua P. Zhou, Jian Shi
Targeting The Brd4/Foxo3a/Cdk6 Axis Sensitizes Akt Inhibition In Luminal Breast Cancer, Jingyi Liu, Weijie Guo, Zhibing Duan, Lei Zeng, Yadi Wu, Yule Chen, Fang Tai, Yifan Wang, Yiwei Lin, Qiang Zhang, Yanling He, Jiong Deng, Rachel L. Stewart, Chi Wang, Pengnian Charles Lin, Saghi Ghaffari, B. Mark Evers, Suling Liu, Ming-Ming Zhou, Binhua P. Zhou, Jian Shi
Molecular and Cellular Biochemistry Faculty Publications
BRD4 assembles transcriptional machinery at gene super-enhancer regions and governs the expression of genes that are critical for cancer progression. However, it remains unclear whether BRD4-mediated gene transcription is required for tumor cells to develop drug resistance. Our data show that prolonged treatment of luminal breast cancer cells with AKT inhibitors induces FOXO3a dephosphorylation, nuclear translocation, and disrupts its association with SirT6, eventually leading to FOXO3a acetylation as well as BRD4 recognition. Acetylated FOXO3a recognizes the BD2 domain of BRD4, recruits the BRD4/RNAPII complex to the CDK6 gene promoter, and induces its transcription. Pharmacological inhibition of either BRD4/FOXO3a association or …
Structure Of The Mouse Trpc4 Ion Channel, Jingjing Duan, Jian Li, Bo Zeng, Gui-Lan Chen, Xiaogang Peng, Yixing Zhang, Jianbin Wang, David E. Clapham, Zongli Li, Jin Zhang
Structure Of The Mouse Trpc4 Ion Channel, Jingjing Duan, Jian Li, Bo Zeng, Gui-Lan Chen, Xiaogang Peng, Yixing Zhang, Jianbin Wang, David E. Clapham, Zongli Li, Jin Zhang
Molecular and Cellular Biochemistry Faculty Publications
Members of the transient receptor potential (TRP) ion channels conduct cations into cells. They mediate functions ranging from neuronally mediated hot and cold sensation to intracellular organellar and primary ciliary signaling. Here we report a cryo-electron microscopy (cryo-EM) structure of TRPC4 in its unliganded (apo) state to an overall resolution of 3.3 Å. The structure reveals a unique architecture with a long pore loop stabilized by a disulfide bond. Beyond the shared tetrameric six-transmembrane fold, the TRPC4 structure deviates from other TRP channels with a unique cytosolic domain. This unique cytosolic N-terminal domain forms extensive aromatic contacts with the TRP …
Profiling Prostate Cancer Therapeutic Resistance, Cameron A. Wade, Natasha Kyprianou
Profiling Prostate Cancer Therapeutic Resistance, Cameron A. Wade, Natasha Kyprianou
Urology Faculty Publications
The major challenge in the treatment of patients with advanced lethal prostate cancer is therapeutic resistance to androgen-deprivation therapy (ADT) and chemotherapy. Overriding this resistance requires understanding of the driving mechanisms of the tumor microenvironment, not just the androgen receptor (AR)-signaling cascade, that facilitate therapeutic resistance in order to identify new drug targets. The tumor microenvironment enables key signaling pathways promoting cancer cell survival and invasion via resistance to anoikis. In particular, the process of epithelial-mesenchymal-transition (EMT), directed by transforming growth factor-β (TGF-β), confers stem cell properties and acquisition of a migratory and invasive phenotype via resistance to anoikis. Our …
Structure Of Full-Length Human Trpm4, Jingjing Duan, Zongli Li, Jian Li, Ana Santa-Cruz, Silvia Sanchez-Martinez, Jin Zhang, David E. Clapham
Structure Of Full-Length Human Trpm4, Jingjing Duan, Zongli Li, Jian Li, Ana Santa-Cruz, Silvia Sanchez-Martinez, Jin Zhang, David E. Clapham
Molecular and Cellular Biochemistry Faculty Publications
Transient receptor potential melastatin subfamily member 4 (TRPM4) is a widely distributed, calcium-activated, monovalent-selective cation channel. Mutations in human TRPM4 (hTRPM4) result in progressive familial heart block. Here, we report the electron cryomicroscopy structure of hTRPM4 in a closed, Na+-bound, apo state at pH 7.5 to an overall resolution of 3.7 Å. Five partially hydrated sodium ions are proposed to occupy the center of the conduction pore and the entrance to the coiled-coil domain. We identify an upper gate in the selectivity filter and a lower gate at the entrance to the cytoplasmic coiled-coil domain. Intramolecular interactions exist …
Kruppel-Like Factor 4-Dependent Staufen1-Mediated Mrna Decay Regulates Cortical Neurogenesis, Byoung-San Moon, Jinlun Bai, Mingyang Cai, Chunming Liu, Jiandang Shi, Wange Lu
Kruppel-Like Factor 4-Dependent Staufen1-Mediated Mrna Decay Regulates Cortical Neurogenesis, Byoung-San Moon, Jinlun Bai, Mingyang Cai, Chunming Liu, Jiandang Shi, Wange Lu
Molecular and Cellular Biochemistry Faculty Publications
Kruppel-like factor 4 (Klf4) is a zinc-finger-containing protein that plays a critical role in diverse cellular physiology. While most of these functions attribute to its role as a transcription factor, it is postulated that Klf4 may play a role other than transcriptional regulation. Here we demonstrate that Klf4 loss in neural progenitor cells (NPCs) leads to increased neurogenesis and reduced self-renewal in mice. In addition, Klf4 interacts with RNA-binding protein Staufen1 (Stau1) and RNA helicase Ddx5/17. They function together as a complex to maintain NPC self-renewal. We report that Klf4 promotes Stau1 recruitment to the 3′-untranslated region of neurogenesis-associated mRNAs, …
Selective Inhibition Of Ctcf Binding By Ias Directs Tet-Mediated Reprogramming Of 5-Hydroxymethylation Patterns In Ias-Transformed Cells, Matthew Rea, Tyler Gripshover, Yvonne N. Fondufe-Mittendorf
Selective Inhibition Of Ctcf Binding By Ias Directs Tet-Mediated Reprogramming Of 5-Hydroxymethylation Patterns In Ias-Transformed Cells, Matthew Rea, Tyler Gripshover, Yvonne N. Fondufe-Mittendorf
Molecular and Cellular Biochemistry Faculty Publications
Methylation at cytosine (5mC) is a fundamental epigenetic DNA modification recently associated with iAs-mediated carcinogenesis. In contrast, the role of 5-hydroxymethylcytosine (5hmC), the oxidation product of 5mC in iAs-mediated carcinogenesis is unknown. Here we assess the hydroxymethylome in iAs-transformed cells, showing that dynamic modulation of hydroxymethylated DNA is associated with specific transcriptional networks. Moreover, this pathologic iAs-mediated carcinogenesis is characterized by a shift toward a higher hydroxymethylation pattern genome-wide. At specific promoters, hydroxymethylation correlated with increased gene expression. Furthermore, this increase in hydroxymethylation occurs concurrently with an upregulation of ten-eleven translocation (TET) enzymes that oxidize 5-methylcytosine (5mC) in DNA. To …
Human Metapneumovirus Induces Formation Of Inclusion Bodies For Efficient Genome Replication And Transcription, Nicolás P. Cifuentes-Muñoz, Jean Branttie, Kerri Beth Slaughter, Rebecca Ellis Dutch
Human Metapneumovirus Induces Formation Of Inclusion Bodies For Efficient Genome Replication And Transcription, Nicolás P. Cifuentes-Muñoz, Jean Branttie, Kerri Beth Slaughter, Rebecca Ellis Dutch
Molecular and Cellular Biochemistry Faculty Publications
Human metapneumovirus (HMPV) causes significant upper and lower respiratory disease in all age groups worldwide. The virus possesses a negative-sense single-stranded RNA genome of approximately 13.3 kb encapsidated by multiple copies of the nucleoprotein (N), giving rise to helical nucleocapsids. In addition, copies of the phosphoprotein (P) and the large RNA polymerase (L) decorate the viral nucleocapsids. After viral attachment, endocytosis, and fusion mediated by the viral glycoproteins, HMPV nucleocapsids are released into the cell cytoplasm. To visualize the subsequent steps of genome transcription and replication, a fluorescence in situ hybridization (FISH) protocol was established to detect different viral RNA …
Tox Regulates Growth, Dna Repair, And Genomic Instability In T-Cell Acute Lymphoblastic Leukemia, Riadh Lobbardi, Jordan Pinder, Barbara Martinez-Pastor, Marina Theodorou, Jessica S. Blackburn, Brian J. Abraham, Yuka Namiki, Marc Mansour, Nouran S. Abdelfattah, Aleksey Molodtsov, Gabriela Alexe, Debra Toiber, Manon De Waard, Esha Jain, Myriam Boukhali, Mattia Lion, Deepak Bhere, Khalid Shah, Alejandro Gutierrez, Kimberly Stegmaier, Lewis B. Silverman, Ruslan I. Sadreyev, John M. Asara, Marjorie A. Oettinger, Wilhelm Haas, A. Thomas Look, Richard A. Young, Raul Mostoslavsky, Graham Dellaire, David M. Langenau
Tox Regulates Growth, Dna Repair, And Genomic Instability In T-Cell Acute Lymphoblastic Leukemia, Riadh Lobbardi, Jordan Pinder, Barbara Martinez-Pastor, Marina Theodorou, Jessica S. Blackburn, Brian J. Abraham, Yuka Namiki, Marc Mansour, Nouran S. Abdelfattah, Aleksey Molodtsov, Gabriela Alexe, Debra Toiber, Manon De Waard, Esha Jain, Myriam Boukhali, Mattia Lion, Deepak Bhere, Khalid Shah, Alejandro Gutierrez, Kimberly Stegmaier, Lewis B. Silverman, Ruslan I. Sadreyev, John M. Asara, Marjorie A. Oettinger, Wilhelm Haas, A. Thomas Look, Richard A. Young, Raul Mostoslavsky, Graham Dellaire, David M. Langenau
Molecular and Cellular Biochemistry Faculty Publications
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of thymocytes. Using a transgenic screen in zebrafish, thymocyte selection–associated high mobility group box protein (TOX) was uncovered as a collaborating oncogenic driver that accelerated T-ALL onset by expanding the initiating pool of transformed clones and elevating genomic instability. TOX is highly expressed in a majority of human T-ALL and is required for proliferation and continued xenograft growth in mice. Using a wide array of functional analyses, we uncovered that TOX binds directly to KU70/80 and suppresses recruitment of this complex to DNA breaks to inhibit nonhomologous end joining (NHEJ) repair. …
Nanoparticle Delivery Of Mir-34a Eradicates Long-Term-Cultured Breast Cancer Stem Cells Via Targeting C22orf28 Directly, Xiaoti Lin, Weiyu Chen, Fengqin Wei, Binhua P. Zhou, Mien-Chie Hung, Xiaoming Xie
Nanoparticle Delivery Of Mir-34a Eradicates Long-Term-Cultured Breast Cancer Stem Cells Via Targeting C22orf28 Directly, Xiaoti Lin, Weiyu Chen, Fengqin Wei, Binhua P. Zhou, Mien-Chie Hung, Xiaoming Xie
Molecular and Cellular Biochemistry Faculty Publications
Rationale: Cancer stem cells (CSCs) have been implicated as the seeds of therapeutic resistance and metastasis, due to their unique abilities of self-renew, wide differentiation potentials and resistance to most conventional therapies. It is a proactive strategy for cancer therapy to eradicate CSCs. Methods: Tumor tissue-derived breast CSCs (BCSC), including XM322 and XM607, were isolated by fluorescence-activated cell sorting (FACS); while cell line-derived BCSC, including MDA-MB-231.SC and MCF-7.SC, were purified by magnetic-activated cell sorting (MACS). Analyses of microRNA and mRNA expression array profiles were performed in multiple breast cell lines. The mentioned nanoparticles were constructed following the standard molecular cloning …
1H, 15N, And 13C Chemical Shift Assignments Of The Regulatory Domain Of Human Calcineurin, Dinesh K. Yadav, Sri Ramya Tata, John Hunt, Erik C. Cook, Trevor P. Creamer, Nicholas C. Fitzkee
1H, 15N, And 13C Chemical Shift Assignments Of The Regulatory Domain Of Human Calcineurin, Dinesh K. Yadav, Sri Ramya Tata, John Hunt, Erik C. Cook, Trevor P. Creamer, Nicholas C. Fitzkee
Center for Structural Biology Faculty Publications
Calcineurin (CaN) plays an important role in T-cell activation, cardiac system development and nervous system function. Previous studies have demonstrated that the regulatory domain (RD) of CaN binds calmodulin (CaM) towards the N-terminal end. Calcium-loaded CaM activates the serine/threonine phosphatase activity of CaN by binding to the RD, although the mechanistic details of this interaction remain unclear. It is thought that CaM binding at the RD displaces the auto-inhibitory domain (AID) from the active site of CaN, activating phosphatase activity. In the absence of calcium-loaded CaM, the RD is disordered, and binding of CaM induces folding in the RD. In …
Transient And Permanent Changes In Dna Methylation Patterns In Inorganic Arsenic-Mediated Epithelial-To-Mesenchymal Transition, Meredith Eckstein, Matthew Rea, Yvonne N. Fondufe-Mittendorf
Transient And Permanent Changes In Dna Methylation Patterns In Inorganic Arsenic-Mediated Epithelial-To-Mesenchymal Transition, Meredith Eckstein, Matthew Rea, Yvonne N. Fondufe-Mittendorf
Molecular and Cellular Biochemistry Faculty Publications
Chronic low dose inorganic arsenic exposure causes cells to take on an epithelial-to-mesenchymal phenotype, which is a crucial process in carcinogenesis. Inorganic arsenic is not a mutagen and thus epigenetic alterations have been implicated in this process. Indeed, during the epithelial-to-mesenchymal transition, morphologic changes to cells correlate with changes in chromatin structure and gene expression, ultimately driving this process. However, studies on the effects of inorganic arsenic exposure/withdrawal on the epithelial-to-mesenchymal transition and the impact of epigenetic alterations in this process are limited. In this study we used high-resolution microarray analysis to measure the changes in DNA methylation in cells …
The Activity Of The Serotonin Receptor 2c Is Regulated By Alternative Splicing, Stefan Stamm, Samuel B. Gruber, Alexander G. Rabchevsky, Ronald B. Emeson
The Activity Of The Serotonin Receptor 2c Is Regulated By Alternative Splicing, Stefan Stamm, Samuel B. Gruber, Alexander G. Rabchevsky, Ronald B. Emeson
Molecular and Cellular Biochemistry Faculty Publications
The central nervous system-specific serotonin receptor 2C (5HT2C) controls key physiological functions, such as food intake, anxiety, and motoneuron activity. Its deregulation is involved in depression, suicidal behavior, and spasticity, making it the target for antipsychotic drugs, appetite controlling substances, and possibly anti-spasm agents. Through alternative pre-mRNA splicing and RNA editing, the 5HT2C gene generates at least 33 mRNA isoforms encoding 25 proteins. The 5HT2C is a G-protein coupled receptor that signals through phospholipase C, influencing the expression of immediate/early genes like c-fos. Most 5HT2C isoforms show constitutive activity, i.e., signal without ligand binding. The constitutive activity of 5HT2C is …
Chloroformate Derivatization For Tracing The Fate Of Amino Acids In Cells And Tissues By Multiple Stable Isotope Resolved Metabolomics (Msirm), Ye Yang, Teresa W. -M. Fan, Andrew N. Lane, Richard M. Higashi
Chloroformate Derivatization For Tracing The Fate Of Amino Acids In Cells And Tissues By Multiple Stable Isotope Resolved Metabolomics (Msirm), Ye Yang, Teresa W. -M. Fan, Andrew N. Lane, Richard M. Higashi
Center for Environmental and Systems Biochemistry Faculty Publications
Amino acids have crucial roles in central metabolism, both anabolic and catabolic. To elucidate these roles, steady-state concentrations of amino acids alone are insufficient, as each amino acid participates in multiple pathways and functions in a complex network, which can also be compartmentalized. Stable Isotope-Resolved Metabolomics (SIRM) is an approach that uses atom-resolved tracking of metabolites through biochemical transformations in cells, tissues, or whole organisms. Using different elemental stable isotopes to label multiple metabolite precursors makes it possible to resolve simultaneously the utilization of these precursors in a single experiment. Conversely, a single precursor labeled with two (or more) different …
Quaternary Interactions And Supercoiling Modulate The Cooperative Dna Binding Of Agt, Manana Melikishvili, Michael G. Fried
Quaternary Interactions And Supercoiling Modulate The Cooperative Dna Binding Of Agt, Manana Melikishvili, Michael G. Fried
Center for Structural Biology Faculty Publications
Human O6-alkylguanine-DNA alkyltransferase (AGT) repairs mutagenic O6-alkylguanine and O4-alkylthymine adducts in single-stranded and duplex DNAs. The search for these lesions, through a vast excess of competing, unmodified genomic DNA, is a mechanistic challenge that may limit the repair rate in vivo. Here, we examine influences of DNA secondary structure and twist on protein–protein interactions in cooperative AGT complexes formed on lesion-free DNAs that model the unmodified parts of the genome. We used a new approach to resolve nearest neighbor (nn) and long-range (lr) components from the ensemble-average cooperativity, ωave. We found …
Mutations In The Transmembrane Domain And Cytoplasmic Tail Of Hendra Virus Fusion Protein Disrupt Virus-Like-Particle Assembly, Nicolás P. Cifuentes-Muñoz, Weina Sun, Greeshma Ray, Phuong Tieu Schmitt, Stacy Webb, Kathleen Gibson, Rebecca Ellis Dutch, Anthony P. Schmitt
Mutations In The Transmembrane Domain And Cytoplasmic Tail Of Hendra Virus Fusion Protein Disrupt Virus-Like-Particle Assembly, Nicolás P. Cifuentes-Muñoz, Weina Sun, Greeshma Ray, Phuong Tieu Schmitt, Stacy Webb, Kathleen Gibson, Rebecca Ellis Dutch, Anthony P. Schmitt
Molecular and Cellular Biochemistry Faculty Publications
Hendra virus (HeV) is a zoonotic paramyxovirus that causes deadly illness in horses and humans. An intriguing feature of HeV is the utilization of endosomal protease for activation of the viral fusion protein (F). Here we investigated how endosomal F trafficking affects HeV assembly. We found that the HeV matrix (M) and F proteins each induced particle release when they were expressed alone but that their coexpression led to coordinated assembly of virus-like particles (VLPs) that were morphologically and physically distinct from M-only or F-only VLPs. Mutations to the F protein transmembrane domain or cytoplasmic tail that disrupted endocytic trafficking …
C/D-Box Snornas Form Methylating And Non-Methylating Ribonucleoprotein Complexes: Old Dogs Show New Tricks, Marina Falaleeva, Justin R. Welden, Marilyn J. Duncan, Stefan Stamm
C/D-Box Snornas Form Methylating And Non-Methylating Ribonucleoprotein Complexes: Old Dogs Show New Tricks, Marina Falaleeva, Justin R. Welden, Marilyn J. Duncan, Stefan Stamm
Molecular and Cellular Biochemistry Faculty Publications
C/D box snoRNAs (SNORDs) are an abundantly expressed class of short, non‐coding RNAs that have been long known to perform 2′‐O‐methylation of rRNAs. However, approximately half of human SNORDs have no predictable rRNA targets, and numerous SNORDs have been associated with diseases that show no defects in rRNAs, among them Prader‐Willi syndrome, Duplication 15q syndrome and cancer. This apparent discrepancy has been addressed by recent studies showing that SNORDs can act to regulate pre‐mRNA alternative splicing, mRNA abundance, activate enzymes, and be processed into shorter ncRNAs resembling miRNAs and piRNAs. Furthermore, recent biochemical studies have shown that a given SNORD …
Perspectives And Expectations In Structural Bioinformatics Of Metalloproteins, Sen Yao, Robert M. Flight, Eric C. Rouchka, Hunter N. B. Moseley
Perspectives And Expectations In Structural Bioinformatics Of Metalloproteins, Sen Yao, Robert M. Flight, Eric C. Rouchka, Hunter N. B. Moseley
Molecular and Cellular Biochemistry Faculty Publications
Recent papers highlight the presence of large numbers of compressed angles in metal ion coordination geometries for metalloprotein entries in the worldwide Protein Data Bank, due mainly to multidentate coordination. The prevalence of these compressed angles has raised the controversial idea that significantly populated aberrant or even novel coordination geometries may exist. Some of these papers have undergone severe criticism, apparently due to views held that only canonical coordination geometries exist in significant numbers. While criticism of controversial ideas is warranted and to be expected, we believe that a line was crossed where unfair criticism was put forth to discredit …
Editorial: Platelet Secretion, Brian Storrie, Sidney W. Whiteheart
Editorial: Platelet Secretion, Brian Storrie, Sidney W. Whiteheart
Molecular and Cellular Biochemistry Faculty Publications
No abstract provided.
Calcium's Role As Nuanced Modulator Of Cellular Physiology In The Brain, Hilaree N. Frazier, Shaniya Maimaiti, Katie L. Anderson, Lawrence D. Brewer, John C. Gant, Nada M. Porter, Olivier Thibault
Calcium's Role As Nuanced Modulator Of Cellular Physiology In The Brain, Hilaree N. Frazier, Shaniya Maimaiti, Katie L. Anderson, Lawrence D. Brewer, John C. Gant, Nada M. Porter, Olivier Thibault
Pharmacology and Nutritional Sciences Faculty Publications
Neuroscientists studying normal brain aging, spinal cord injury, Alzheimer’s disease (AD) and other neurodegenerative diseases have focused considerable effort on carefully characterizing intracellular perturbations in calcium dynamics or levels. At the cellular level, calcium is known for controlling life and death and orchestrating most events in between. For many years, intracellular calcium has been recognized as an essential ion associated with nearly all cellular functions from cell growth to degeneration. Often the emphasis is on the negative impact of calcium dysregulation and the typical worse-case-scenario leading inevitably to cell death. However, even high amplitude calcium transients, when executed acutely can …
Sex Differences In The Subjective Effects Of Oral Δ9-Thc In Cannabis Users, Jessica S. Fogel, Thomas H. Kelly, Philip M. Westgate, Joshua A. Lile
Sex Differences In The Subjective Effects Of Oral Δ9-Thc In Cannabis Users, Jessica S. Fogel, Thomas H. Kelly, Philip M. Westgate, Joshua A. Lile
Behavioral Science Faculty Publications
Previous studies suggest that there are sex differences in endocannabinoid function and the response to exogenous cannabinoids, though data from clinical studies comparing acute cannabinoid effects in men and women under controlled laboratory conditions are limited. To further explore these potential differences, data from 30 cannabis users (N=18 M, 12 F) who completed previous Δ9-tetrahydrocannabinol (Δ9-THC) discrimination studies were combined for this retrospective analysis. In each study, subjects learned to discriminate between oral Δ9-THC and placebo and then received a range of Δ9-THC doses (0, 5, 15 and a “high” dose of …
The Nuts And Bolts Of The Platelet Release Reaction, Smita Joshi, Sidney W. Whiteheart
The Nuts And Bolts Of The Platelet Release Reaction, Smita Joshi, Sidney W. Whiteheart
Molecular and Cellular Biochemistry Faculty Publications
Secretion is essential to many of the roles that platelets play in the vasculature, e.g., thrombosis, angiogenesis, and inflammation, enabling platelets to modulate the microenvironment at sites of vascular lesions with a myriad of bioactive molecules stored in their granules. Past studies demonstrate that granule cargo release is mediated by Soluble NSF Attachment Protein Receptor (SNARE) proteins, which are required for granule-plasma membrane fusion. Several SNARE regulators, which control when, where, and how the SNAREs interact, have been identified in platelets. Additionally, platelet SNAREs are controlled by post-translational modifications, e.g., phosphorylation and acylation. Although there have been many …
P70s6k1 (S6k1)-Mediated Phosphorylation Regulates Phosphatidylinositol 4-Phosphate 5-Kinase Type I Γ Degradation And Cell Invasion, Naser Jafari, Qiaodan Zheng, Liqing Li, Wei Li, Lei Qi, Jianyong Xiao, Tianyan Gao, Cai Huang
P70s6k1 (S6k1)-Mediated Phosphorylation Regulates Phosphatidylinositol 4-Phosphate 5-Kinase Type I Γ Degradation And Cell Invasion, Naser Jafari, Qiaodan Zheng, Liqing Li, Wei Li, Lei Qi, Jianyong Xiao, Tianyan Gao, Cai Huang
Markey Cancer Center Faculty Publications
Phosphatidylinositol 4-phosphate 5-kinase type I γ (PIPKIγ90) ubiquitination and subsequent degradation regulate focal adhesion assembly, cell migration, and invasion. However, it is unknown how upstream signals control PIPKIγ90 ubiquitination or degradation. Here we show that p70S6K1 (S6K1), a downstream target of mechanistic target of rapamycin (mTOR), phosphorylates PIPKIγ90 at Thr-553 and Ser-555 and that S6K1-mediated PIPKIγ90 phosphorylation is essential for cell migration and invasion. Moreover, PIPKIγ90 phosphorylation is required for the development of focal adhesions and invadopodia, key machineries for cell migration and invasion. Surprisingly, substitution of Thr-553 and Ser-555 …
Pleckstrin Homology (Ph) Domain Leucine-Rich Repeat Protein Phosphatase Controls Cell Polarity By Negatively Regulating The Activity Of Atypical Protein Kinase C, Xiaopeng Xiong, Xin Li, Yang-An Wen, Tianyan Gao
Pleckstrin Homology (Ph) Domain Leucine-Rich Repeat Protein Phosphatase Controls Cell Polarity By Negatively Regulating The Activity Of Atypical Protein Kinase C, Xiaopeng Xiong, Xin Li, Yang-An Wen, Tianyan Gao
Markey Cancer Center Faculty Publications
The proper establishment of epithelial polarity allows cells to sense and respond to signals that arise from the microenvironment in a spatiotemporally controlled manner. Atypical PKCs (aPKCs) are implicated as key regulators of epithelial polarity. However, the molecular mechanism underlying the negative regulation of aPKCs remains largely unknown. In this study, we demonstrated that PH domain leucine-rich repeat protein phosphatase (PHLPP), a novel family of Ser/Thr protein phosphatases, plays an important role in regulating epithelial polarity by controlling the phosphorylation of both aPKC isoforms. Altered expression of PHLPP1 or PHLPP2 disrupted polarization of Caco2 cells grown in 3D cell cultures …
Lipophosphoglycans From Leishmania Amazonensis Strains Display Immunomodulatory Properties Via Tlr4 And Do Not Affect Sand Fly Infection, Paula M. Nogueira, Rafael R. Assis, Ana C. Torrecilhas, Elvira M. Saraiva, Natália L. Pessoa, Marco A. Campos, Eric F. Marialva, Cláudia M. Ríos-Velasquez, Felipe A. Pessoa, Nágila F. Secundino, Jerônimo N. Rugani, Elsa Nieves, Salvatore J. Turco, Maria N. Melo, Rodrigo P. Soares
Lipophosphoglycans From Leishmania Amazonensis Strains Display Immunomodulatory Properties Via Tlr4 And Do Not Affect Sand Fly Infection, Paula M. Nogueira, Rafael R. Assis, Ana C. Torrecilhas, Elvira M. Saraiva, Natália L. Pessoa, Marco A. Campos, Eric F. Marialva, Cláudia M. Ríos-Velasquez, Felipe A. Pessoa, Nágila F. Secundino, Jerônimo N. Rugani, Elsa Nieves, Salvatore J. Turco, Maria N. Melo, Rodrigo P. Soares
Molecular and Cellular Biochemistry Faculty Publications
The immunomodulatory properties of lipophosphoglycans (LPG) from New World species of Leishmania have been assessed in Leishmania infantum and Leishmania braziliensis, the causative agents of visceral and cutaneous leishmaniasis, respectively. This glycoconjugate is highly polymorphic among species with variation in sugars that branch off the conserved Gal(β1,4)Man(α1)-PO4 backbone of repeat units. Here, the immunomodulatory activity of LPGs from Leishmania amazonensis, the causative agent of diffuse cutaneous leishmaniasis, was evaluated in two strains from Brazil. One strain (PH8) was originally isolated from the sand fly and the other (Josefa) was isolated from a human case. The ability of …
The Hiv-1 Tat Protein Is Monomethylated At Lysine 71 By The Lysine Methyltransferase Kmt7, Ibraheem Ali, Holly Ramage, Daniela Boehm, Lynnette M. A. Dirk, Naoki Sakane, Kazuki Hanada, Sara Pagans, Katrin Kaehlcke, Katherine Aull, Leor Weinberger, Raymond Trievel, Martina Schnoelzer, Masafumi Kamada, Robert L. Houtz, Melanie Ott
The Hiv-1 Tat Protein Is Monomethylated At Lysine 71 By The Lysine Methyltransferase Kmt7, Ibraheem Ali, Holly Ramage, Daniela Boehm, Lynnette M. A. Dirk, Naoki Sakane, Kazuki Hanada, Sara Pagans, Katrin Kaehlcke, Katherine Aull, Leor Weinberger, Raymond Trievel, Martina Schnoelzer, Masafumi Kamada, Robert L. Houtz, Melanie Ott
Horticulture Faculty Publications
The HIV-1 transactivator protein Tat is a critical regulator of HIV transcription primarily enabling efficient elongation of viral transcripts. Its interactions with RNA and various host factors are regulated by ordered, transient post-translational modifications. Here, we report a novel Tat modification, monomethylation at lysine 71 (K71). We found that Lys-71 monomethylation (K71me) is catalyzed by KMT7, a methyltransferase that also targets lysine 51 (K51) in Tat. Using mass spectrometry, in vitro enzymology, and modification-specific antibodies, we found that KMT7 monomethylates both Lys-71 and Lys-51 in Tat. K71me is important for full Tat transactivation, as KMT7 knockdown impaired the transcriptional activity …