LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 6 of total 6

Search options

  1. Article ; Online: Targeting Polyphosphate Kinases in the Fight against Pseudomonas aeruginosa.

    Baijal, Kanchi / Downey, Michael

    mBio

    2021  Volume 12, Issue 4, Page(s) e0147721

    Abstract: Polyphosphate (polyP) is a universally conserved molecule that plays critical roles in managing bacterial stress responses, in addition to biofilm formation and virulence. The enzymes that make polyphosphate molecules are called polyphosphate kinases ( ... ...

    Abstract Polyphosphate (polyP) is a universally conserved molecule that plays critical roles in managing bacterial stress responses, in addition to biofilm formation and virulence. The enzymes that make polyphosphate molecules are called polyphosphate kinases (PPKs). Since these enzymes are not conserved in higher eukaryotes, PPKs make excellent therapeutic targets. In a recent paper in
    MeSH term(s) Bacteria ; Polyphosphates ; Pseudomonas aeruginosa ; Virulence
    Chemical Substances Polyphosphates
    Language English
    Publishing date 2021-08-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 2557172-2
    ISSN 2150-7511 ; 2161-2129
    ISSN (online) 2150-7511
    ISSN 2161-2129
    DOI 10.1128/mBio.01477-21
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  2. Article ; Online: The promises of lysine polyphosphorylation as a regulatory modification in mammals are tempered by conceptual and technical challenges.

    Baijal, Kanchi / Downey, Michael

    BioEssays : news and reviews in molecular, cellular and developmental biology

    2021  Volume 43, Issue 7, Page(s) e2100058

    Abstract: Polyphosphate (polyP) is a ubiquitous biomolecule thought to be present in all cells on Earth. PolyP is deceivingly simple, consisting of repeated units of inorganic phosphates polymerized in long energy-rich chains. PolyP is involved in diverse ... ...

    Abstract Polyphosphate (polyP) is a ubiquitous biomolecule thought to be present in all cells on Earth. PolyP is deceivingly simple, consisting of repeated units of inorganic phosphates polymerized in long energy-rich chains. PolyP is involved in diverse functions in mammalian systems-from cell signaling to blood clotting. One exciting avenue of research is a new nonenzymatic post-translational modification, termed lysine polyphosphorylation, wherein polyP chains are covalently attached to lysine residues of target proteins. While the modification was first characterized in budding yeast, recent work has now identified the first human targets. There is significant promise in this area of biomedical research, but a number of technical issues and knowledge gaps present challenges to rapid progress. In this review, the current state of the field is summarized and existing roadblocks related to the study of lysine polyphosphorylation in higher eukaryotes are introduced. It is discussed how limited methods to identify targets of polyphosphorylation are further impacted by low concentration, unknown regulatory enzymes, and sequestration of polyP into compartments in mammalian systems. Furthermore, suggestions on how these obstacles could be addressed or what their physiological relevance may be within mammalian cells are presented.
    MeSH term(s) Animals ; Humans ; Lysine/metabolism ; Mammals/metabolism ; Phosphorylation ; Polyphosphates/metabolism ; Protein Processing, Post-Translational
    Chemical Substances Polyphosphates ; Lysine (K3Z4F929H6)
    Language English
    Publishing date 2021-05-16
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 50140-2
    ISSN 1521-1878 ; 0265-9247
    ISSN (online) 1521-1878
    ISSN 0265-9247
    DOI 10.1002/bies.202100058
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 2024: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article: The promises of lysine polyphosphorylation as a regulatory modification in mammals are tempered by conceptual and technical challenges

    Baijal, Kanchi / Downey, Michael

    BioEssays. 2021 July, v. 43, no. 7

    2021  

    Abstract: Polyphosphate (polyP) is a ubiquitous biomolecule thought to be present in all cells on Earth. PolyP is deceivingly simple, consisting of repeated units of inorganic phosphates polymerized in long energy‐rich chains. PolyP is involved in diverse ... ...

    Abstract Polyphosphate (polyP) is a ubiquitous biomolecule thought to be present in all cells on Earth. PolyP is deceivingly simple, consisting of repeated units of inorganic phosphates polymerized in long energy‐rich chains. PolyP is involved in diverse functions in mammalian systems—from cell signaling to blood clotting. One exciting avenue of research is a new nonenzymatic post‐translational modification, termed lysine polyphosphorylation, wherein polyP chains are covalently attached to lysine residues of target proteins. While the modification was first characterized in budding yeast, recent work has now identified the first human targets. There is significant promise in this area of biomedical research, but a number of technical issues and knowledge gaps present challenges to rapid progress. In this review, the current state of the field is summarized and existing roadblocks related to the study of lysine polyphosphorylation in higher eukaryotes are introduced. It is discussed how limited methods to identify targets of polyphosphorylation are further impacted by low concentration, unknown regulatory enzymes, and sequestration of polyP into compartments in mammalian systems. Furthermore, suggestions on how these obstacles could be addressed or what their physiological relevance may be within mammalian cells are presented.
    Keywords biomedical research ; chemical bonding ; eukaryotic cells ; humans ; lysine ; post-translational modification ; yeasts
    Language English
    Dates of publication 2021-07
    Publishing place John Wiley & Sons, Ltd
    Document type Article
    Note JOURNAL ARTICLE
    ZDB-ID 50140-2
    ISSN 1521-1878 ; 0265-9247
    ISSN (online) 1521-1878
    ISSN 0265-9247
    DOI 10.1002/bies.202100058
    Database NAL-Catalogue (AGRICOLA)

    Full text online

    More links

    Kategorien

    In stock of ZB MED Bonn / Germany

    Z 2009/501: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  4. Article ; Online: Polyphosphate kinase regulates LPS structure and polymyxin resistance during starvation in E. coli.

    Baijal, Kanchi / Abramchuk, Iryna / Herrera, Carmen M / Mah, Thien-Fah / Trent, M Stephen / Lavallée-Adam, Mathieu / Downey, Michael

    PLoS biology

    2024  Volume 22, Issue 3, Page(s) e3002558

    Abstract: Polyphosphates (polyP) are chains of inorganic phosphates that can reach over 1,000 residues in length. In Escherichia coli, polyP is produced by the polyP kinase (PPK) and is thought to play a protective role during the response to cellular stress. ... ...

    Abstract Polyphosphates (polyP) are chains of inorganic phosphates that can reach over 1,000 residues in length. In Escherichia coli, polyP is produced by the polyP kinase (PPK) and is thought to play a protective role during the response to cellular stress. However, the molecular pathways impacted by PPK activity and polyP accumulation remain poorly characterized. In this work, we used label-free mass spectrometry to study the response of bacteria that cannot produce polyP (Δppk) during starvation to identify novel pathways regulated by PPK. In response to starvation, we found 92 proteins significantly differentially expressed between wild-type and Δppk mutant cells. Wild-type cells were enriched for proteins related to amino acid biosynthesis and transport, while Δppk mutants were enriched for proteins related to translation and ribosome biogenesis, suggesting that without PPK, cells remain inappropriately primed for growth even in the absence of the required building blocks. From our data set, we were particularly interested in Arn and EptA proteins, which were down-regulated in Δppk mutants compared to wild-type controls, because they play a role in lipid A modifications linked to polymyxin resistance. Using western blotting, we confirm differential expression of these and related proteins in K-12 strains and a uropathogenic isolate, and provide evidence that this mis-regulation in Δppk cells stems from a failure to induce the BasRS two-component system during starvation. We also show that Δppk mutants unable to up-regulate Arn and EptA expression lack the respective L-Ara4N and pEtN modifications on lipid A. In line with this observation, loss of ppk restores polymyxin sensitivity in resistant strains carrying a constitutively active basR allele. Overall, we show a new role for PPK in lipid A modification during starvation and provide a rationale for targeting PPK to sensitize bacteria towards polymyxin treatment. We further anticipate that our proteomics work will provide an important resource for researchers interested in the diverse pathways impacted by PPK.
    MeSH term(s) Escherichia coli/metabolism ; Lipopolysaccharides/metabolism ; Lipid A/metabolism ; Polyphosphates/metabolism ; Phosphotransferases (Phosphate Group Acceptor)
    Chemical Substances polyphosphate kinase (EC 2.7.4.1) ; Lipopolysaccharides ; Lipid A ; Polyphosphates ; Phosphotransferases (Phosphate Group Acceptor) (EC 2.7.4.-)
    Language English
    Publishing date 2024-03-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2126776-5
    ISSN 1545-7885 ; 1544-9173
    ISSN (online) 1545-7885
    ISSN 1544-9173
    DOI 10.1371/journal.pbio.3002558
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 6193: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  5. Article: Proteomics analysis reveals a role for

    Baijal, Kanchi / Abramchuk, Iryna / Herrera, Carmen M / Stephen Trent, M / Lavallée-Adam, Mathieu / Downey, Michael

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Polyphosphates (polyP) are chains of inorganic phosphates that can reach over 1000 residues in length. ... ...

    Abstract Polyphosphates (polyP) are chains of inorganic phosphates that can reach over 1000 residues in length. In
    Language English
    Publishing date 2023-07-06
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.07.06.546892
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  6. Article ; Online: A Broad Response to Intracellular Long-Chain Polyphosphate in Human Cells.

    Bondy-Chorney, Emma / Abramchuk, Iryna / Nasser, Rawan / Holinier, Charlotte / Denoncourt, Alix / Baijal, Kanchi / McCarthy, Liam / Khacho, Mireille / Lavallée-Adam, Mathieu / Downey, Michael

    Cell reports

    2020  Volume 33, Issue 4, Page(s) 108318

    Abstract: Polyphosphates (polyPs) are long chains of inorganic phosphates linked by phosphoanhydride bonds. They are found in all kingdoms of life, playing roles in cell growth, infection, and blood coagulation. Unlike in bacteria and lower eukaryotes, the ... ...

    Abstract Polyphosphates (polyPs) are long chains of inorganic phosphates linked by phosphoanhydride bonds. They are found in all kingdoms of life, playing roles in cell growth, infection, and blood coagulation. Unlike in bacteria and lower eukaryotes, the mammalian enzymes responsible for polyP metabolism are largely unexplored. We use RNA sequencing (RNA-seq) and mass spectrometry to define a broad impact of polyP produced inside of mammalian cells via ectopic expression of the E. coli polyP synthetase PPK. We find that multiple cellular compartments can support accumulation of polyP to high levels. Overproduction of polyP is associated with reprogramming of both the transcriptome and proteome, including activation of the ERK1/2-EGR1 signaling axis. Finally, fractionation analysis shows that polyP accumulation results in relocalization of nuclear/cytoskeleton proteins, including targets of non-enzymatic lysine polyphosphorylation. Our work demonstrates that internally produced polyP can activate diverse signaling pathways in human cells.
    MeSH term(s) Humans ; Nuclear Proteins/metabolism ; Polyphosphates/metabolism
    Chemical Substances Nuclear Proteins ; Polyphosphates
    Language English
    Publishing date 2020-11-26
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2020.108318
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

To top