13 results on '"Bowman, James W."'
Search Results
2. TXNIP-mediated crosstalk between oxidative stress and glucose metabolism.
- Author
-
Kim, Stephanie, Ge, Jianning, Kim, Dokyun, Lee, Jae Jin, Choi, Youn Jung, Chen, Weiqiang, Bowman, James W., Foo, Suan-Sin, Chang, Lin-Chun, Liang, Qiming, Hara, Daiki, Choi, Inpyo, Kim, Myung Hee, Eoh, Hyungjin, and Jung, Jae U.
- Subjects
GLUCOSE metabolism ,OXIDATIVE stress ,PENTOSE phosphate pathway ,ENDOCYTOSIS ,THIOREDOXIN-interacting protein ,HOMEOSTASIS ,METABOLIC disorders - Abstract
Thioredoxin-interacting protein (TXNIP) has emerged as a key player in cancer and diabetes since it targets thioredoxin (TRX)-mediated redox regulation and glucose transporter (GLUT)-mediated metabolism. TXNIP consists of two arrestin (ARR, N-ARR and C-ARR) domains at its amino-terminus and two PPxY (PY) motifs and a di-leucine (LL) motif for endocytosis at its carboxyl-terminus. Here, we report that TXNIP shuffles between TRX and GLUTs to regulate homeostasis of intracellular oxidative stress and glucose metabolism. While TXNIP functions as a gatekeeper of TRX by default, it robustly interacted with class I GLUTs through its C-ARR domain upon increase of intracellular reactive oxygen species. This interaction prompted the surface expression downregulation and lysosomal degradation of GLUTs by its carboxyl-terminal LL endocytic signaling motif to attenuate glucose uptake. Consequently, TXNIP expression significantly limited glucose uptake, leading to the suppression of glycolysis, hexosamine biosynthesis, and the pentose phosphate pathway. Our findings establish a fundamental link between ROS and glucose metabolism through TXNIP and provide a promising target for the drug development against GLUT-related metabolic disorders. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
3. Autophagy during viral infection — a double-edged sword
- Author
-
Choi, Younho, Bowman, James W., and Jung, Jae U.
- Published
- 2018
- Full Text
- View/download PDF
4. Asian Zika virus strains target CD14+ blood monocytes and induce M2-skewed immunosuppression during pregnancy
- Author
-
Foo, Suan-Sin, Chen, Weiqiang, Chan, Yen, Bowman, James W., Chang, Lin-Chun, Choi, Younho, Yoo, Ji Seung, Ge, Jianning, Cheng, Genhong, Bonnin, Alexandre, Nielsen-Saines, Karin, Brasil, Patrícia, and Jung, Jae U.
- Published
- 2017
- Full Text
- View/download PDF
5. Next to Newest, Gooney!
- Author
-
Bowman, James W.
- Published
- 1970
6. IgG targeting distinct seasonal coronavirus- conserved SARS-CoV-2 spike subdomains correlates with differential COVID-19 disease outcomes.
- Author
-
Garrido, Jose L., Medina, Matías A., Bravo, Felipe, McGee, Sarah, Fuentes-Villalobos, Francisco, Calvo, Mario, Pinos, Yazmin, Bowman, James W., Bahl, Christopher D., Barria, Maria Ines, Brachman, Rebecca A., and Alvarez, Raymond A.
- Abstract
Despite SARS-CoV-2 being a "novel" virus, early detection of anti-spike IgG in severe COVID-19 patients may be caused by the amplification of humoral memory responses against seasonal coronaviruses. Here, we examine this phenomenon by characterizing anti-spike IgG responses in non-hospitalized convalescent individuals across a spectrum of COVID-19 severity. We observe that disease severity positively correlates with anti-spike IgG levels, IgG cross-reactivity against other betacoronaviruses (β-CoVs), and FcγR activation. Analysis of IgG targeting β-CoV-conserved and non-conserved immunodominant epitopes within the SARS-CoV-2 spike protein revealed epitope-specific relationships: IgG targeting the conserved heptad repeat (HR) 2 region significantly correlates with milder disease, while targeting the conserved S2′FP region correlates with more severe disease. Furthermore, a lower HR2-to-S2′FP IgG-binding ratio correlates with greater disease severity, with ICU-hospitalized COVID-19 patients showing the lowest HR2/S2′FP ratios. These findings suggest that HR2/S2′FP IgG profiles may predict disease severity and offer insight into protective versus deleterious humoral recall responses. [Display omitted] • COVID-19 severity correlates with FcγR activity and betacoronavirus cross-reactivity • IgG recall responses may be protective or deleterious, depending on epitope targeting • Conserved regions: targeting HR2 correlates with mild disease, S2′FP with severe disease • HR2-to-S2′FP IgG ratio may predict COVID-19 severity Garrido et al. find that humoral memory responses against seasonal coronaviruses contribute to COVID-19 disease severity, conferring either protection or risk, depending on epitope targeting. These data suggest an explanatory mechanism underlying the atypical bimodality of COVID-19 disease severity, the observation of which was previously obscured by aggregate epitope analysis. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
7. Regulation Where Autophagy Intersects the Inflammasome.
- Author
-
Rodgers, Mary A., Bowman, James W., Liang, Qiming, and Jung, Jae U.
- Subjects
- *
AUTOPHAGY , *NATURAL immunity , *ORGANELLES , *MITOCHONDRIAL DNA , *REACTIVE oxygen species - Abstract
Significance: The autophagy and inflammasome pathways are ancient innate immune mechanisms for controlling invading pathogens that are linked by mutual regulation. In addition to controlling the metabolic homeostasis of the cell through nutrient recycling, the 'self-eating' process of autophagy is also responsible for the degradation of damaged organelles, cells, and pathogens to protect the integrity of the organism. As a cytosolic pathogen recognition receptor (PRR) complex, the inflammasome both induces and is induced by autophagy through direct interactions with autophagy proteins or through the effects of secondary molecules, such as mitochondrial reactive oxygen species and mitochondrial DNA. Recent Advances: While the molecular mechanisms of inflammasome activation and regulation are largely unknown, much of the current knowledge has been established through investigation of the role of autophagy in innate immunity. Likewise, regulatory proteins in the NOD-like receptor family, which includes inflammasome PRRs, are able to stimulate autophagy in response to the presence of a pathogen. Critical Issues: Many of the newly uncovered links between autophagy and inflammasomes have raised new questions about the mechanisms controlling inflammasome function, which are highlighted in this review. Future Directions: Our basic understanding of the mutual regulation of inflammasomes and autophagy will be essential for designing therapeutics for chronic inflammatory diseases, especially those for which autophagy and inflammasome genes have already been linked. Antioxid. Redox Signal. 20, 495-506. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
8. Preventing fires with high temperature vaporizers.
- Author
-
Bowman, James W. and Perkins, Rowan P.
- Published
- 1990
- Full Text
- View/download PDF
9. Complete combinatorial mutational enumeration of a protein functional site enables sequence-landscape mapping and identifies highly-mutated variants that retain activity.
- Author
-
Colom MS, Vučinić J, Adolf-Bryfogle J, Bowman JW, Verel S, Moczygemba I, Schiex T, Simoncini D, and Bahl CD
- Subjects
- Humans, Binding Sites, COVID-19 virology, COVID-19 genetics, Protein Binding, Artificial Intelligence, Spike Glycoprotein, Coronavirus genetics, Spike Glycoprotein, Coronavirus chemistry, Spike Glycoprotein, Coronavirus metabolism, Angiotensin-Converting Enzyme 2 metabolism, Angiotensin-Converting Enzyme 2 chemistry, Angiotensin-Converting Enzyme 2 genetics, SARS-CoV-2 genetics, SARS-CoV-2 chemistry, SARS-CoV-2 metabolism, Mutation
- Abstract
Understanding how proteins evolve under selective pressure is a longstanding challenge. The immensity of the search space has limited efforts to systematically evaluate the impact of multiple simultaneous mutations, so mutations have typically been assessed individually. However, epistasis, or the way in which mutations interact, prevents accurate prediction of combinatorial mutations based on measurements of individual mutations. Here, we use artificial intelligence to define the entire functional sequence landscape of a protein binding site in silico, and we call this approach Complete Combinatorial Mutational Enumeration (CCME). By leveraging CCME, we are able to construct a comprehensive map of the evolutionary connectivity within this functional sequence landscape. As a proof of concept, we applied CCME to the ACE2 binding site of the SARS-CoV-2 spike protein receptor binding domain. We selected representative variants from across the functional sequence landscape for testing in the laboratory. We identified variants that retained functionality to bind ACE2 despite changing over 40% of evaluated residue positions, and the variants now escape binding and neutralization by monoclonal antibodies. This work represents a crucial initial stride toward achieving precise predictions of pathogen evolution, opening avenues for proactive mitigation., (© 2024 The Protein Society.)
- Published
- 2024
- Full Text
- View/download PDF
10. Complete Combinatorial Mutational Enumeration of a protein functional site enables sequence-landscape mapping and identifies highly-mutated variants that retain activity.
- Author
-
Colom MS, Vucinic J, Adolf-Bryfogle J, Bowman JW, Verel S, Moczygemba I, Schiex T, Simoncini D, and Bahl CD
- Abstract
Understanding how proteins evolve under selective pressure is a longstanding challenge. The immensity of the search space has limited efforts to systematically evaluate the impact of multiple simultaneous mutations, so mutations have typically been assessed individually. However, epistasis, or the way in which mutations interact, prevents accurate prediction of combinatorial mutations based on measurements of individual mutations. Here, we use artificial intelligence to define the entire functional sequence landscape of a protein binding site in silico , and we call this approach Complete Combinatorial Mutational Enumeration (CCME). By leveraging CCME, we are able to construct a comprehensive map of the evolutionary connectivity within this functional sequence landscape. As a proof of concept, we applied CCME to the ACE2 binding site of the SARS-CoV-2 spike protein receptor binding domain. We selected representative variants from across the functional sequence landscape for testing in the laboratory. We identified variants that retained functionality to bind ACE2 despite changing over 40% of evaluated residue positions, and the variants now escape binding and neutralization by monoclonal antibodies. This work represents a crucial initial stride towards achieving precise predictions of pathogen evolution, opening avenues for proactive mitigation., Competing Interests: Competing interests MSC, JTB, IM and CDB own stock in AI Proteins, Inc.
- Published
- 2023
- Full Text
- View/download PDF
11. A Talented Duo: IFIT1 and IFIT3 Patrol Viral RNA Caps.
- Author
-
Choi YJ, Bowman JW, and Jung JU
- Subjects
- Adaptor Proteins, Signal Transducing, Cryopyrin-Associated Periodic Syndromes, Humans, Intracellular Signaling Peptides and Proteins, Protein Biosynthesis, RNA Caps, RNA-Binding Proteins, Carrier Proteins genetics, RNA, Viral
- Abstract
Hosts respond to viral infection by expressing interferon-stimulated genes, of which IFITs are potent inhibitors of viral RNA translation. Johnson et al. (2018) solved the structure of the IFIT1-IFIT3 complex bound cap 0 RNA and explored their concerted antiviral activity., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
12. Architecture of the type IV coupling protein complex of Legionella pneumophila.
- Author
-
Kwak MJ, Kim JD, Kim H, Kim C, Bowman JW, Kim S, Joo K, Lee J, Jin KS, Kim YG, Lee NK, Jung JU, and Oh BH
- Subjects
- Bacterial Proteins genetics, Crystallography, X-Ray, Gene Expression Regulation, Bacterial, Legionella pneumophila genetics, Legionella pneumophila metabolism, Models, Molecular, Multiprotein Complexes metabolism, Protein Domains, Type IV Secretion Systems genetics, Type IV Secretion Systems metabolism, Bacterial Proteins chemistry, Bacterial Proteins metabolism, Legionella pneumophila chemistry, Multiprotein Complexes chemistry, Type IV Secretion Systems chemistry
- Abstract
Many bacteria, including Legionella pneumophila, rely on the type IV secretion system to translocate a repertoire of effector proteins into the hosts for their survival and growth. Type IV coupling protein (T4CP) is a hexameric ATPase that links translocating substrates to the transenvelope secretion conduit. Yet, how a large number of effector proteins are selectively recruited and processed by T4CPs remains enigmatic. DotL, the T4CP of L. pneumophila, contains an ATPase domain and a C-terminal extension whose function is unknown. Unlike T4CPs involved in plasmid DNA translocation, DotL appeared to function by forming a multiprotein complex with four other proteins. Here, we show that the C-terminal extension of DotL interacts with DotN, IcmS, IcmW and an additionally identified subunit LvgA, and that this pentameric assembly binds Legionella effector proteins. We determined the crystal structure of this assembly and built an architecture of the T4CP holocomplex by combining a homology model of the ATPase domain of DotL. The holocomplex is a hexamer of a bipartite structure composed of a membrane-proximal ATPase domain and a membrane-distal substrate-recognition assembly. The presented information demonstrates the architecture and functional dissection of the multiprotein T4CP complexes and provides important insights into their substrate recruitment and processing.
- Published
- 2017
- Full Text
- View/download PDF
13. The linear ubiquitin assembly complex (LUBAC) is essential for NLRP3 inflammasome activation.
- Author
-
Rodgers MA, Bowman JW, Fujita H, Orazio N, Shi M, Liang Q, Amatya R, Kelly TJ, Iwai K, Ting J, and Jung JU
- Subjects
- Animals, Carrier Proteins genetics, Common Variable Immunodeficiency genetics, Common Variable Immunodeficiency immunology, GTPase-Activating Proteins genetics, GTPase-Activating Proteins immunology, Humans, Immunity, Innate drug effects, Inflammasomes genetics, Interleukin-1beta genetics, Interleukin-1beta immunology, Intracellular Signaling Peptides and Proteins genetics, Intracellular Signaling Peptides and Proteins immunology, Lipopolysaccharides toxicity, Macrophages cytology, Mice, Mice, Knockout, Multiprotein Complexes genetics, NF-kappa B genetics, NF-kappa B immunology, NLR Family, Pyrin Domain-Containing 3 Protein, Ubiquitin-Protein Ligases genetics, Ubiquitin-Protein Ligases immunology, Carrier Proteins immunology, Immunity, Innate physiology, Inflammasomes immunology, Macrophages immunology, Multiprotein Complexes immunology, Ubiquitination physiology
- Abstract
Linear ubiquitination is a newly discovered posttranslational modification that is currently restricted to a small number of known protein substrates. The linear ubiquitination assembly complex (LUBAC), consisting of HOIL-1L, HOIP, and Sharpin, has been reported to activate NF-κB-mediated transcription in response to receptor signaling by ligating linear ubiquitin chains to Nemo and Rip1. Despite recent advances, the detailed roles of LUBAC in immune cells remain elusive. We demonstrate a novel HOIL-1L function as an essential regulator of the activation of the NLRP3/ASC inflammasome in primary bone marrow-derived macrophages (BMDMs) independently of NF-κB activation. Mechanistically, HOIL-1L is required for assembly of the NLRP3/ASC inflammasome and the linear ubiquitination of ASC, which we identify as a novel LUBAC substrate. Consequently, we find that HOIL-1L(-/-) mice have reduced IL-1β secretion in response to in vivo NLRP3 stimulation and survive lethal challenge with LPS. Together, these data demonstrate that linear ubiquitination is required for NLRP3 inflammasome activation, defining the molecular events of NLRP3 inflammasome activation and expanding the role of LUBAC as an innate immune regulator. Furthermore, our observation is clinically relevant because patients lacking HOIL-1L expression suffer from pyogenic bacterial immunodeficiency, providing a potential new therapeutic target for enhancing inflammation in immunodeficient patients., (© 2014 Rodgers et al.)
- Published
- 2014
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.