, a bio/informatics shared resource is still "open for business" - Visit the CDS website


Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 10 of 136

Publication Record

Connections

A dileucine motif in the COOH-terminal domain of NKCC1 targets the cotransporter to the plasma membrane.
Koumangoye R, Omer S, Delpire E
(2019) Am J Physiol Cell Physiol 316: C545-C558
MeSH Terms: Animals, Cell Membrane, Dogs, Leucine, Madin Darby Canine Kidney Cells, Peptide Fragments, Protein Transport, Solute Carrier Family 12, Member 2
Show Abstract · Added April 2, 2019
Na-K-2Cl cotransporter-1 (NKCC1) mediates the electroneutral transport of Na, K, and Cl and is normally localized to the basolateral membrane of polarized epithelial cells. We recently reported the first known solute carrier family 12 member 2 ( SLC12A2) mutation (we call NKCC1-DFX) that causes epithelial dysfunction in an undiagnosed disease program case. The heterozygous mutation leads to truncation of the COOH-terminal tail of the cotransporter, resulting in both mutant and wild-type cotransporters being mistrafficked to the apical membrane of polarized epithelial cells. Here we demonstrate by using consecutive truncations and site-directed mutagenesis of the COOH-terminal domain of NKCC1 that truncation of NKCC1 COOH domain uncouples the cotransporter from the lateral membrane. We identify a dileucine motif that, when mutated, leads to cotransporter accumulation in the cytoplasm and mistrafficking to the apical/subapical region of epithelial cells, thereby recapitulating the phenotype observed with the patient mutation. We show that truncation deletion and LL substitution mutants are trafficked out of the endoplasmic reticulum and trans-Golgi network but accumulate in early and late endosomes where they are degraded.
0 Communities
1 Members
0 Resources
8 MeSH Terms
Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas.
Schaub FX, Dhankani V, Berger AC, Trivedi M, Richardson AB, Shaw R, Zhao W, Zhang X, Ventura A, Liu Y, Ayer DE, Hurlin PJ, Cherniack AD, Eisenman RN, Bernard B, Grandori C, Cancer Genome Atlas Network
(2018) Cell Syst 6: 282-300.e2
MeSH Terms: Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Basic Helix-Loop-Helix Transcription Factors, Biomarkers, Tumor, Carcinogenesis, Chromatin, Computational Biology, Genes, myc, Genomics, Humans, Neoplasms, Oncogenes, Proteomics, Proto-Oncogene Proteins c-myc, Repressor Proteins, Signal Transduction, Transcription Factors
Show Abstract · Added October 30, 2019
Although the MYC oncogene has been implicated in cancer, a systematic assessment of alterations of MYC, related transcription factors, and co-regulatory proteins, forming the proximal MYC network (PMN), across human cancers is lacking. Using computational approaches, we define genomic and proteomic features associated with MYC and the PMN across the 33 cancers of The Cancer Genome Atlas. Pan-cancer, 28% of all samples had at least one of the MYC paralogs amplified. In contrast, the MYC antagonists MGA and MNT were the most frequently mutated or deleted members, proposing a role as tumor suppressors. MYC alterations were mutually exclusive with PIK3CA, PTEN, APC, or BRAF alterations, suggesting that MYC is a distinct oncogenic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such as immune response and growth factor signaling; chromatin, translation, and DNA replication/repair were conserved pan-cancer. This analysis reveals insights into MYC biology and is a reference for biomarkers and therapeutics for cancers with alterations of MYC or the PMN.
Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
0 Communities
1 Members
0 Resources
MeSH Terms
SIRT4 Is a Lysine Deacylase that Controls Leucine Metabolism and Insulin Secretion.
Anderson KA, Huynh FK, Fisher-Wellman K, Stuart JD, Peterson BS, Douros JD, Wagner GR, Thompson JW, Madsen AS, Green MF, Sivley RM, Ilkayeva OR, Stevens RD, Backos DS, Capra JA, Olsen CA, Campbell JE, Muoio DM, Grimsrud PA, Hirschey MD
(2017) Cell Metab 25: 838-855.e15
MeSH Terms: Amidohydrolases, Amino Acid Sequence, Animals, Carbon-Carbon Ligases, Glucose, HEK293 Cells, Homeostasis, Humans, Insulin, Insulin Resistance, Insulin Secretion, Leucine, Lysine, Metabolic Flux Analysis, Mice, Inbred C57BL, Mice, Knockout, Mitochondrial Proteins, Models, Molecular, Phylogeny, Sirtuins
Show Abstract · Added April 18, 2017
Sirtuins are NAD-dependent protein deacylases that regulate several aspects of metabolism and aging. In contrast to the other mammalian sirtuins, the primary enzymatic activity of mitochondrial sirtuin 4 (SIRT4) and its overall role in metabolic control have remained enigmatic. Using a combination of phylogenetics, structural biology, and enzymology, we show that SIRT4 removes three acyl moieties from lysine residues: methylglutaryl (MG)-, hydroxymethylglutaryl (HMG)-, and 3-methylglutaconyl (MGc)-lysine. The metabolites leading to these post-translational modifications are intermediates in leucine oxidation, and we show a primary role for SIRT4 in controlling this pathway in mice. Furthermore, we find that dysregulated leucine metabolism in SIRT4KO mice leads to elevated basal and stimulated insulin secretion, which progressively develops into glucose intolerance and insulin resistance. These findings identify a robust enzymatic activity for SIRT4, uncover a mechanism controlling branched-chain amino acid flux, and position SIRT4 as a crucial player maintaining insulin secretion and glucose homeostasis during aging.
Copyright © 2017 Elsevier Inc. All rights reserved.
0 Communities
1 Members
0 Resources
20 MeSH Terms
Tissue sodium accumulation and peripheral insulin sensitivity in maintenance hemodialysis patients.
Deger SM, Wang P, Fissell R, Ellis CD, Booker C, Sha F, Morse JL, Stewart TG, Gore JC, Siew ED, Titze J, Ikizler TA
(2017) J Cachexia Sarcopenia Muscle 8: 500-507
MeSH Terms: Adult, Biomarkers, Blood Glucose, Body Composition, Female, Glucose, Humans, Insulin, Insulin Resistance, Leucine, Magnetic Resonance Imaging, Male, Middle Aged, Muscle, Skeletal, Organ Specificity, Renal Dialysis, Skin, Sodium
Show Abstract · Added April 6, 2017
BACKGROUND - Recent data suggest that sodium (Na ) is stored in the muscle and skin without commensurate water retention in maintenance hemodialysis (MHD) patients. In this study, we hypothesized that excessive Na accumulation would be associated with abnormalities in peripheral insulin action.
METHODS - Eleven MHD patients and eight controls underwent hyperinsulinemic-euglycemic-euaminoacidemic clamp studies to measure glucose (GDR) and leucine disposal rates (LDR), as well as lower left leg Na magnetic resonance imaging to measure Na concentration in the muscle and skin tissue.
RESULTS - The median GDR and LDR levels were lower, and the median muscle Na concentration was higher in MHD patients compared with controls. No significant difference was found regarding skin Na concentration between group comparisons. Linear regression revealed inverse relationships between muscle Na concentration and GDR and LDR in MHD patients, whereas no relationship was observed in controls. There was no association between skin Na content and GDR or LDR in either MHD patients or controls.
CONCLUSIONS - These data suggest that excessive muscle Na content might be a determinant of IR in MHD patients, although the causality and mechanisms remain to be proven.
© 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.
0 Communities
2 Members
0 Resources
18 MeSH Terms
Investigation of the Complete Suite of the Leucine and Isoleucine Isomers: Toward Prediction of Ion Mobility Separation Capabilities.
Dodds JN, May JC, McLean JA
(2017) Anal Chem 89: 952-959
MeSH Terms: Isoleucine, Isomerism, Leucine, Mass Spectrometry, Molecular Conformation
Show Abstract · Added December 17, 2018
In this study we investigated 11 isomers with the molecular formula CHNO (m/z 131) to ascertain the potential of utilizing drift tube ion mobility mass spectrometry to aid in the separation of isomeric mixtures. This study of small molecules provides a detailed examination of the application of uniform field ion mobility for a narrow scope of isomers with variations in both bond coordination and stereochemistry. For small molecules, it was observed that in general constitutional isomers are more readily separated by uniform field mobility in comparison to stereoisomers such as enantiomers or diastereomers. Diastereomers exhibited differences in their collision cross section (CCS), but were unresolvable in a mixture, whereas the enantiomers studied did not exhibit statistically different CCS values. A mathematical relationship relating the CCS to resolving power was developed in order to predict the required ion mobility resolving power needed to separate the various isomer classes. For the majority of isomers evaluated in this study, a uniform field-based resolving power of 100 was predicted to be sufficient to resolve over half (∼60%) of all hypothetical isomer pairs, including leucine and isoleucine, whereas their stereoisomers (d- and l-forms) are predicted to be significantly more challenging, if not impossible, to separate by conventional drift tube techniques.
0 Communities
1 Members
0 Resources
MeSH Terms
Nup100 regulates replicative life span by mediating the nuclear export of specific tRNAs.
Lord CL, Ospovat O, Wente SR
(2017) RNA 23: 365-377
MeSH Terms: Active Transport, Cell Nucleus, Basic-Leucine Zipper Transcription Factors, Blotting, Northern, Cell Division, Cell Nucleus, Culture Media, Gene Expression Regulation, Fungal, In Situ Hybridization, Fluorescence, Karyopherins, Nuclear Pore, Nuclear Pore Complex Proteins, RNA, Fungal, RNA, Transfer, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Time Factors
Show Abstract · Added April 14, 2017
Nuclear pore complexes (NPCs), which are composed of nucleoporins (Nups) and regulate transport between the nucleus and cytoplasm, significantly impact the replicative life span (RLS) of We previously reported that deletion of the nonessential gene increases RLS, although the molecular basis for this effect was unknown. In this study, we find that nuclear tRNA accumulation contributes to increased longevity in Δ cells. Fluorescence in situ hybridization (FISH) experiments demonstrate that several specific tRNAs accumulate in the nuclei of Δ mutants. Protein levels of the transcription factor Gcn4 are increased when is deleted, and is required for the elevated life spans of Δ mutants, similar to other previously described tRNA export and ribosomal mutants. Northern blots indicate that tRNA splicing and aminoacylation are not significantly affected in Δ cells, suggesting that Nup100 is largely required for nuclear export of mature, processed tRNAs. Distinct tRNAs accumulate in the nuclei of Δ and Δ mutants, while Los1-GFP nucleocytoplasmic shuttling is unaffected by Nup100. Thus, we conclude that Nup100 regulates tRNA export in a manner distinct from Los1 or Msn5. Together, these experiments reveal a novel Nup100 role in the tRNA life cycle that impacts the life span.
© 2017 Lord et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.
0 Communities
1 Members
0 Resources
16 MeSH Terms
Interaction of Gcn4 with target gene chromatin is modulated by proteasome function.
Howard GC, Tansey WP
(2016) Mol Biol Cell 27: 2735-41
MeSH Terms: Adenosine Triphosphatases, Basic-Leucine Zipper Transcription Factors, Cell Cycle Proteins, Chromatin, DNA-Binding Proteins, Molecular Chaperones, Proteasome Endopeptidase Complex, Proteolysis, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Transcription Factors, Transcriptional Activation, Ubiquitin, Ubiquitination, Valosin Containing Protein
Show Abstract · Added March 26, 2019
The ubiquitin-proteasome system (UPS) influences gene transcription in multiple ways. One way in which the UPS affects transcription centers on transcriptional activators, the function of which can be stimulated by components of the UPS that also trigger their destruction. Activation of transcription by the yeast activator Gcn4, for example, is attenuated by mutations in the ubiquitin ligase that mediates Gcn4 ubiquitylation or by inhibition of the proteasome, leading to the idea that ubiquitin-mediated proteolysis of Gcn4 is required for its activity. Here we probe the steps in Gcn4 activity that are perturbed by disruption of the UPS. We show that the ubiquitylation machinery and the proteasome control different steps in Gcn4 function and that proteasome activity is required for the ability of Gcn4 to bind to its target genes in the context of chromatin. Curiously, the effect of proteasome inhibition on Gcn4 activity is suppressed by mutations in the ubiquitin-selective chaperone Cdc48, revealing that proteolysis per se is not required for Gcn4 activity. Our data highlight the role of Cdc48 in controlling promoter occupancy by Gcn4 and support a model in which ubiquitylation of activators-not their destruction-is important for function.
© 2016 Howard and Tansey. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).
0 Communities
1 Members
0 Resources
MeSH Terms
Identification of Susceptibility Loci and Genes for Colorectal Cancer Risk.
Zeng C, Matsuda K, Jia WH, Chang J, Kweon SS, Xiang YB, Shin A, Jee SH, Kim DH, Zhang B, Cai Q, Guo X, Long J, Wang N, Courtney R, Pan ZZ, Wu C, Takahashi A, Shin MH, Matsuo K, Matsuda F, Gao YT, Oh JH, Kim S, Jung KJ, Ahn YO, Ren Z, Li HL, Wu J, Shi J, Wen W, Yang G, Li B, Ji BT, Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), Brenner H, Schoen RE, Küry S, Colorectal Transdisciplinary (CORECT) Study, Gruber SB, Schumacher FR, Stenzel SL, Colon Cancer Family Registry (CCFR), Casey G, Hopper JL, Jenkins MA, Kim HR, Jeong JY, Park JW, Tajima K, Cho SH, Kubo M, Shu XO, Lin D, Zeng YX, Zheng W
(2016) Gastroenterology 150: 1633-1645
MeSH Terms: Adult, Aged, Asian Continental Ancestry Group, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Case-Control Studies, Colorectal Neoplasms, Eukaryotic Initiation Factor-3, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Qb-SNARE Proteins, Ribosomal Proteins, Risk Factors, Steroid 17-alpha-Hydroxylase, Suppressor of Cytokine Signaling Proteins, Young Adult
Show Abstract · Added May 4, 2017
BACKGROUND & AIMS - Known genetic factors explain only a small fraction of genetic variation in colorectal cancer (CRC). We conducted a genome-wide association study to identify risk loci for CRC.
METHODS - This discovery stage included 8027 cases and 22,577 controls of East-Asian ancestry. Promising variants were evaluated in studies including as many as 11,044 cases and 12,047 controls. Tumor-adjacent normal tissues from 188 patients were analyzed to evaluate correlations of risk variants with expression levels of nearby genes. Potential functionality of risk variants were evaluated using public genomic and epigenomic databases.
RESULTS - We identified 4 loci associated with CRC risk; P values for the most significant variant in each locus ranged from 3.92 × 10(-8) to 1.24 × 10(-12): 6p21.1 (rs4711689), 8q23.3 (rs2450115, rs6469656), 10q24.3 (rs4919687), and 12p13.3 (rs11064437). We also identified 2 risk variants at loci previously associated with CRC: 10q25.2 (rs10506868) and 20q13.3 (rs6061231). These risk variants, conferring an approximate 10%-18% increase in risk per allele, are located either inside or near protein-coding genes that include transcription factor EB (lysosome biogenesis and autophagy), eukaryotic translation initiation factor 3, subunit H (initiation of translation), cytochrome P450, family 17, subfamily A, polypeptide 1 (steroidogenesis), splA/ryanodine receptor domain and SOCS box containing 2 (proteasome degradation), and ribosomal protein S2 (ribosome biogenesis). Gene expression analyses showed a significant association (P < .05) for rs4711689 with transcription factor EB, rs6469656 with eukaryotic translation initiation factor 3, subunit H, rs11064437 with splA/ryanodine receptor domain and SOCS box containing 2, and rs6061231 with ribosomal protein S2.
CONCLUSIONS - We identified susceptibility loci and genes associated with CRC risk, linking CRC predisposition to steroid hormone, protein synthesis and degradation, and autophagy pathways and providing added insight into the mechanism of CRC pathogenesis.
Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.
0 Communities
2 Members
0 Resources
21 MeSH Terms
The MYC-WDR5 Nexus and Cancer.
Thomas LR, Foshage AM, Weissmiller AM, Tansey WP
(2015) Cancer Res 75: 4012-5
MeSH Terms: Antineoplastic Agents, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Chromatin Assembly and Disassembly, DNA, DNA Methylation, Drug Discovery, Epigenesis, Genetic, Gene Expression Regulation, Neoplastic, Genes, myc, Histone-Lysine N-Methyltransferase, Histones, Humans, Models, Genetic, Molecular Targeted Therapy, Neoplasm Proteins, Neoplasms, Protein Binding, Proto-Oncogene Proteins c-myc, Repressor Proteins, Signal Transduction
Show Abstract · Added March 26, 2019
The MYC oncogenes encode a family of transcription factors that feature prominently in cancer. MYC proteins are overexpressed or deregulated in a majority of malignancies and drive tumorigenesis by inducing widespread transcriptional reprogramming that promotes cell proliferation, metabolism, and genomic instability. The ability of MYC to regulate transcription depends on its dimerization with MAX, which creates a DNA-binding domain that recognizes specific sequences in the regulatory elements of MYC target genes. Recently, we discovered that recognition of target genes by MYC also depends on its interaction with WDR5, a WD40-repeat protein that exists as part of several chromatin-regulatory complexes. Here, we discuss how interaction of MYC with WDR5 could create an avidity-based chromatin recognition mechanism that allows MYC to select its target genes in response to both genetic and epigenetic determinants. We rationalize how the MYC-WDR5 interaction provides plasticity in target gene selection by MYC and speculate on the biochemical and genomic contexts in which this interaction occurs. Finally, we discuss how properties of the MYC-WDR5 interface make it an attractive point for discovery of small-molecule inhibitors of MYC function in cancer cells.
©2015 American Association for Cancer Research.
0 Communities
1 Members
0 Resources
MeSH Terms
Effective treatment of allergic airway inflammation with Helicobacter pylori immunomodulators requires BATF3-dependent dendritic cells and IL-10.
Engler DB, Reuter S, van Wijck Y, Urban S, Kyburz A, Maxeiner J, Martin H, Yogev N, Waisman A, Gerhard M, Cover TL, Taube C, Müller A
(2014) Proc Natl Acad Sci U S A 111: 11810-5
MeSH Terms: Allergens, Animals, Antigens, Bacterial, Asthma, Bacterial Proteins, Basic-Leucine Zipper Transcription Factors, Dendritic Cells, Disease Models, Animal, Helicobacter pylori, Humans, Immune Tolerance, Immunologic Factors, Interleukin-10, Interleukin-18, Mice, Mice, Inbred C57BL, Mice, Knockout, Repressor Proteins, T-Lymphocytes, Regulatory, gamma-Glutamyltransferase
Show Abstract · Added January 25, 2015
The prevalence of allergic asthma and other atopic diseases has reached epidemic proportions in large parts of the developed world. The gradual loss of the human indigenous microbiota has been held responsible for this trend. The bacterial pathogen Helicobacter pylori is a constituent of the normal gastric microbiota whose presence has been inversely linked to allergy and asthma in humans and experimental models. Here we show that oral or i.p. tolerization with H. pylori extract prevents the airway hyperresponsiveness, bronchoalveolar eosinophilia, pulmonary inflammation, and Th2 cytokine production that are hallmarks of allergen-induced asthma in mice. Asthma protection is not conferred by extracts from other enteropathogens and requires a heat-sensitive H. pylori component and the DC-intrinsic production of IL-10. The basic leucine zipper ATF-like 3 (BATF3)-dependent CD103(+)CD11b(-) dendritic cell lineage is enriched in the lungs of protected mice and strictly required for protection. Two H. pylori persistence determinants, the γ-glutamyl-transpeptidase GGT and the vacuolating cytotoxin VacA, are required and sufficient for asthma protection and can be administered in purified form to prevent asthma. In conclusion, we provide preclinical evidence for the concept that the immunomodulatory properties of H. pylori can be exploited for tolerization strategies aiming to prevent allergen-induced asthma.
0 Communities
1 Members
0 Resources
20 MeSH Terms