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Start Over Author "Lewis A." Journal journal of biological chemistry
2,919 results on '"Lewis A."'

1. Bridging lipid metabolism and mitochondrial genome maintenance.

Author

Boone, Casadora and Lewis, Samantha

Subjects
lipid metabolism, lipotoxicity, mitochondria, mitochondrial DNA (mtDNA), mitochondrial metabolism, Humans, Lipid Metabolism, Genome, Mitochondrial, DNA, Mitochondrial, Animals, Mitochondria, Endoplasmic Reticulum
Abstract

Mitochondria are the nexus of cellular energy metabolism and major signaling hubs that integrate information from within and without the cell to implement cell function. Mitochondria harbor a distinct polyploid genome, mitochondrial DNA (mtDNA), that encodes respiratory chain components required for energy production. MtDNA mutation and depletion have been linked to obesity and metabolic syndrome in humans. At the cellular and subcellular levels, mtDNA synthesis is coordinated by membrane contact sites implicated in lipid transfer from the endoplasmic reticulum, tying genome maintenance to lipid storage and homeostasis. Here, we examine the relationship between mtDNA and lipid trafficking, the influence of lipotoxicity on mtDNA integrity, and how lipid metabolism may be disrupted in primary mtDNA disease.

Published
2024

6. Dirigent isoflavene-forming PsPTS2: 3D structure, stereochemical, and kinetic characterization comparison with pterocarpan-forming PsPTS1 homolog in pea

Author

Meng, Qingyan, Moinuddin, Syed G.A., Celoy, Rhodesia M., Smith, Clyde A., Young, Robert P., Costa, Michael A., Freeman, Rachel A., Fukaya, Masashi, Kim, Doo Nam, Cort, John R., Hawes, Martha C., van Etten, Hans D., Pandey, Pankaj, Chittiboyina, Amar G., Ferreira, Daneel, Davin, Laurence B., and Lewis, Norman G.

Published
2024
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9. Manganese co-localizes with calcium and phosphorus in Chlamydomonas acidocalcisomes and is mobilized in manganese-deficient conditions

Author

Tsednee, Munkhtsetseg, Castruita, Madeli, Salomé, Patrice A, Sharma, Ajay, Lewis, Brianne E, Schmollinger, Stefan R, Strenkert, Daniela, Holbrook, Kristen, Otegui, Marisa S, Khatua, Kaustav, Das, Sayani, Datta, Ankona, Chen, Si, Ramon, Christina, Ralle, Martina, Weber, Peter K, Stemmler, Timothy L, Pett-Ridge, Jennifer, Hoffman, Brian M, and Merchant, Sabeeha S

Subjects
Chemical Sciences, Affordable and Clean Energy, Calcium, Chlamydomonas, Ions, Manganese, Phosphorus, Vacuoles, X-Ray Absorption Spectroscopy, algae, antioxidant, calcium, histidine, imaging, lysosomal acidification, lysosome, manganese, metal homeostasis, H plus -PPase, NRAMP, organelle, photosynthesis, polyphosphate, H+-PPase, Biological Sciences, Medical and Health Sciences, Biochemistry & Molecular Biology, Biological sciences, Biomedical and clinical sciences, Chemical sciences
Abstract

Exposing cells to excess metal concentrations well beyond the cellular quota is a powerful tool for understanding the molecular mechanisms of metal homeostasis. Such improved understanding may enable bioengineering of organisms with improved nutrition and bioremediation capacity. We report here that Chlamydomonas reinhardtii can accumulate manganese (Mn) in proportion to extracellular supply, up to 30-fold greater than its typical quota and with remarkable tolerance. As visualized by X-ray fluorescence microscopy and nanoscale secondary ion MS (nanoSIMS), Mn largely co-localizes with phosphorus (P) and calcium (Ca), consistent with the Mn-accumulating site being an acidic vacuole, known as the acidocalcisome. Vacuolar Mn stores are accessible reserves that can be mobilized in Mn-deficient conditions to support algal growth. We noted that Mn accumulation depends on cellular polyphosphate (polyP) content, indicated by 1) a consistent failure of C. reinhardtii vtc1 mutant strains, which are deficient in polyphosphate synthesis, to accumulate Mn and 2) a drastic reduction of the Mn storage capacity in P-deficient cells. Rather surprisingly, X-ray absorption spectroscopy, EPR, and electron nuclear double resonance revealed that only little Mn2+ is stably complexed with polyP, indicating that polyP is not the final Mn ligand. We propose that polyPs are a critical component of Mn accumulation in Chlamydomonas by driving Mn relocation from the cytosol to acidocalcisomes. Within these structures, polyP may, in turn, escort vacuolar Mn to a number of storage ligands, including phosphate and phytate, and other, yet unidentified, compounds.

Published
2019

21. Human RNA Polymerase II Promoter Recruitment in Vitro Is Regulated by O-Linked N-Acetylglucosaminyltransferase (OGT)*

Author

Lewis, Brian A, Burlingame, Alma L, and Myers, Samuel A

Subjects
Biochemistry and Cell Biology, Biological Sciences, Genetics, 1.1 Normal biological development and functioning, Underpinning research, Humans, In Vitro Techniques, N-Acetylglucosaminyltransferases, Promoter Regions, Genetic, RNA Polymerase II, gene regulation, O-GlcNAcylation, O-linked N-acetylglucosamine (O-GlcNAc) transferase, RNA polymerase II, transcription, Chemical Sciences, Medical and Health Sciences, Biochemistry & Molecular Biology, Biological sciences, Biomedical and clinical sciences, Chemical sciences
Abstract

Although the O-linked N-acetylglucosamine (O-GlcNAc) modification of the RNA polymerase II C-terminal domain was described 20 years ago, the function of this RNA polymerase II (pol II) species is not known. We show here that an O-GlcNAcylated pol II species (pol IIγ) exists on promoters in vitro Inhibition of O-GlcNAc-transferase activity and O-GlcNAcylation prevents pol II entry into the promoter, and O-GlcNAc removal from pol II is an ATP-dependent step during initiation. These data indicate that O-GlcNAc-transferase activity is essential for RNA pol II promoter recruitment and that pol II goes through a cycling of O-GlcNAcylation at the promoter. Mass spectrometry shows that serine residues 2 and 5 of the pol II C-terminal domain are O-GlcNAcylated, suggesting an overlap with the transcription factor IIH (TFIIH)-dependent serine 5 phosphorylation events during initiation and P-TEFb (positive transcriptional elongation factor b) events during elongation. These data provide unexpected and important insights into the role of a previously ill-defined species of RNA polymerase II in regulating transcription.

Published
2016

23. Mechanistic insights into cancer cell killing through interaction of phosphodiesterase 3A and schlafen family member 12

Author

Wu, Xiaoyun, Schnitzler, Gavin R., Gao, Galen F., Diamond, Brett, Baker, Andrew R., Kaplan, Bethany, Williamson, Kaylyn, Westlake, Lindsay, Lorrey, Selena, Lewis, Timothy A., Garvie, Colin W., Lange, Martin, Hayat, Sikander, Seidel, Henrik, Doench, John, Cherniack, Andrew D., Kopitz, Charlotte, Meyerson, Matthew, and Greulich, Heidi

Published
2020
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24. The extracellular sulfatase SULF2 promotes liver tumorigenesis by stimulating assembly of a promoter-looping GLI1-STAT3 transcriptional complex

Author

Carr, Ryan M., Romecin Duran, Paola A., Tolosa, Ezequiel J., Ma, Chenchao, Oseini, Abdul M., Moser, Catherine D., Banini, Bubu A., Huang, Jianbo, Asumda, Faizal, Dhanasekaran, Renumathy, Graham, Rondell P., Toruner, Merih D., Safgren, Stephanie L., Almada, Luciana L., Wang, Shaoqing, Patnaik, Mrinal M., Roberts, Lewis R., and Fernandez-Zapico, Martin E.

Published
2020
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29. Protein Tyrosine Phosphatase 1B Regulates Pyruvate Kinase M2 Tyrosine Phosphorylation*

Author

Bettaieb, Ahmed, Bakke, Jesse, Nagata, Naoto, Matsuo, Kosuke, Xi, Yannan, Liu, Siming, AbouBechara, Daniel, Melhem, Ramzi, Stanhope, Kimber, Cummings, Bethany, Graham, James, Bremer, Andrew, Zhang, Sheng, Lyssiotis, Costas A, Zhang, Zhong-Yin, Cantley, Lewis C, Havel, Peter J, and Haj, Fawaz G

Subjects
Biochemistry and Cell Biology, Biological Sciences, Diabetes, Nutrition, Obesity, Metabolic and endocrine, 3T3-L1 Cells, Adipose Tissue, Brown, Adult, Aged, Amino Acid Substitution, Animals, Diet, High-Fat, Energy Metabolism, Gene Knockdown Techniques, Glucose Intolerance, Humans, Insulin Resistance, Macaca mulatta, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Middle Aged, Phosphorylation, Phosphotyrosine, Protein Interaction Domains and Motifs, Protein Interaction Mapping, Protein Processing, Post-Translational, Protein Tyrosine Phosphatase, Non-Receptor Type 1, Pyruvate Kinase, Signal Transduction, Adipocyte, Metabolism, Tyrosine Protein Phosphatase, Chemical Sciences, Medical and Health Sciences, Biochemistry & Molecular Biology, Biological sciences, Biomedical and clinical sciences, Chemical sciences
Abstract

Protein-tyrosine phosphatase 1B (PTP1B) is a physiological regulator of glucose homeostasis and adiposity and is a drug target for the treatment of obesity and diabetes. Here we identify pyruvate kinase M2 (PKM2) as a novel PTP1B substrate in adipocytes. PTP1B deficiency leads to increased PKM2 total tyrosine and Tyr(105) phosphorylation in cultured adipocytes and in vivo. Substrate trapping and mutagenesis studies identify PKM2 Tyr-105 and Tyr-148 as key sites that mediate PTP1B-PKM2 interaction. In addition, in vitro analyses illustrate a direct effect of Tyr-105 phosphorylation on PKM2 activity in adipocytes. Importantly, PTP1B pharmacological inhibition increased PKM2 Tyr-105 phosphorylation and decreased PKM2 activity. Moreover, PKM2 Tyr-105 phosphorylation is regulated nutritionally, decreasing in adipose tissue depots after high-fat feeding. Further, decreased PKM2 Tyr-105 phosphorylation correlates with the development of glucose intolerance and insulin resistance in rodents, non-human primates, and humans. Together, these findings identify PKM2 as a novel substrate of PTP1B and provide new insights into the regulation of adipose PKM2 activity.

Published
2013

30. Differential Dorso-ventral Distributions of Kv4.2 and HCN Proteins Confer Distinct Integrative Properties to Hippocampal CA1 Pyramidal Cell Distal Dendrites*

Author

Marcelin, Béatrice, Lugo, Joaquin N, Brewster, Amy L, Liu, Zhiqiang, Lewis, Alan S, McClelland, Shawn, Chetkovich, Dane M, Baram, Tallie Z, Anderson, Anne E, Becker, Albert, Esclapez, Monique, and Bernard, Christophe

Subjects
Neurosciences, Underpinning research, 1.1 Normal biological development and functioning, Neurological, Animals, Cyclic Nucleotide-Gated Cation Channels, Dendrites, Down-Regulation, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels, Ion Channels, Nerve Tissue Proteins, Organ Specificity, Potassium Channels, Pyramidal Cells, Rats, Shal Potassium Channels, Transcription, Genetic, Up-Regulation, Chemical Sciences, Biological Sciences, Medical and Health Sciences, Biochemistry & Molecular Biology
Abstract

The dorsal and ventral regions of the hippocampus perform different functions. Whether the integrative properties of hippocampal cells reflect this heterogeneity is unknown. We focused on dendrites where most synaptic input integration takes place. We report enhanced backpropagation and theta resonance and decreased summation of synaptic inputs in ventral versus dorsal CA1 pyramidal cell distal dendrites. Transcriptional Kv4.2 down-regulation and post-transcriptional hyperpolarization-activated cyclic AMP-gated channel (HCN1/2) up-regulation may underlie these differences, respectively. Our results reveal differential dendritic integrative properties along the dorso-ventral axis, reflecting diverse computational needs.

Published
2012

33. Trafficking and Gating of Hyperpolarization-activated Cyclic Nucleotide-gated Channels Are Regulated by Interaction with Tetratricopeptide Repeat-containing Rab8b-interacting Protein (TRIP8b) and Cyclic AMP at Distinct Sites*

Author

Han, Ye, Noam, Yoav, Lewis, Alan S, Gallagher, Johnie J, Wadman, Wytse J, Baram, Tallie Z, and Chetkovich, Dane M

Subjects
Underpinning research, 1.1 Normal biological development and functioning, Animals, Cyclic AMP, Cyclic Nucleotide-Gated Cation Channels, HEK293 Cells, Humans, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels, Ion Channel Gating, Membrane Proteins, Mice, Peroxins, Potassium Channels, Protein Binding, Protein Transport, Rats, Up-Regulation, Chemical Sciences, Biological Sciences, Medical and Health Sciences, Biochemistry & Molecular Biology
Abstract

Ion channel trafficking and gating are often influenced by interactions with auxiliary subunits. Tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b) is an auxiliary subunit for neuronal hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. TRIP8b interacts directly with two distinct sites of HCN channel pore-forming subunits to control channel trafficking and gating. Here we use mutagenesis combined with electrophysiological studies to define and distinguish the functional importance of the HCN/TRIP8b interaction sites. Interaction with the last three amino acids of the HCN1 C terminus governed the effect of TRIP8b on channel trafficking, whereas TRIP8b interaction with the HCN1 cyclic nucleotide binding domain (CNBD) affected trafficking and gating. Biochemical studies revealed that direct interaction between TRIP8b and the HCN1 CNBD was disrupted by cAMP and that TRIP8b binding to the CNBD required an arginine residue also necessary for cAMP binding. In accord, increasing cAMP levels in cells antagonized the up-regulation of HCN1 channels mediated by a TRIP8b construct binding the CNBD exclusively. These data illustrate the distinct roles of the two TRIP8b-HCN interaction domains and suggest that TRIP8b and cAMP may directly compete for binding the HCN CNBD to control HCN channel gating, kinetics, and trafficking.

Published
2011

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