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  1. Article ; Online: The Deubiquitinase OTUB1 Is a Key Regulator of Energy Metabolism.

    Ruiz-Serrano, Amalia / Boyle, Christina N / Monné Rodríguez, Josep M / Günter, Julia / Jucht, Agnieszka E / Pfundstein, Svende / Bapst, Andreas M / Lutz, Thomas A / Wenger, Roland H / Scholz, Carsten C

    International journal of molecular sciences

    2022  Volume 23, Issue 3

    Abstract: Dysregulated energy metabolism is a major contributor to a multitude of pathologies, including obesity and diabetes. Understanding the regulation of metabolic homeostasis is of utmost importance for the identification of therapeutic targets for the ... ...

    Abstract Dysregulated energy metabolism is a major contributor to a multitude of pathologies, including obesity and diabetes. Understanding the regulation of metabolic homeostasis is of utmost importance for the identification of therapeutic targets for the treatment of metabolically driven diseases. We previously identified the deubiquitinase OTUB1 as substrate for the cellular oxygen sensor factor-inhibiting HIF (FIH) with regulatory effects on cellular energy metabolism, but the physiological relevance of OTUB1 is unclear. Here, we report that the induced global deletion of OTUB1 in adult mice (
    MeSH term(s) Adenosine Triphosphate/metabolism ; Adenylate Kinase/metabolism ; Animals ; Blood Glucose ; Body Weight ; Cell Size ; Cells, Cultured ; Cysteine Endopeptidases/genetics ; Cysteine Endopeptidases/metabolism ; Energy Metabolism ; Fibroblasts/cytology ; Fibroblasts/drug effects ; Fibroblasts/metabolism ; Gene Deletion ; Insulin/administration & dosage ; Insulin/adverse effects ; Insulin Resistance/genetics ; Mice ; Mixed Function Oxygenases/metabolism ; Phosphorylation ; Proto-Oncogene Proteins c-akt/metabolism
    Chemical Substances Blood Glucose ; Insulin ; Adenosine Triphosphate (8L70Q75FXE) ; Mixed Function Oxygenases (EC 1.-) ; factor inhibiting hypoxia-inducible factor 1, mouse (EC 1.-) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Adenylate Kinase (EC 2.7.4.3) ; Cysteine Endopeptidases (EC 3.4.22.-) ; Otub1 protein, mouse (EC 3.4.22.-)
    Language English
    Publishing date 2022-01-28
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms23031536
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: OTUB1 regulates lung development, adult lung tissue homeostasis, and respiratory control.

    Ruiz-Serrano, Amalia / Monné Rodríguez, Josep M / Günter, Julia / Sherman, Samantha P M / Jucht, Agnieszka E / Fluechter, Pascal / Volkova, Yulia L / Pfundstein, Svende / Pellegrini, Giovanni / Wagner, Carsten A / Schneider, Christoph / Wenger, Roland H / Scholz, Carsten C

    FASEB journal : official publication of the Federation of American Societies for Experimental Biology

    2021  Volume 35, Issue 12, Page(s) e22039

    Abstract: OTUB1 is one of the most highly expressed deubiquitinases, counter-regulating the two most abundant ubiquitin chain types. OTUB1 expression is linked to the development and progression of lung cancer and idiopathic pulmonary fibrosis in humans. However, ... ...

    Abstract OTUB1 is one of the most highly expressed deubiquitinases, counter-regulating the two most abundant ubiquitin chain types. OTUB1 expression is linked to the development and progression of lung cancer and idiopathic pulmonary fibrosis in humans. However, the physiological function of OTUB1 is unknown. Here, we show that constitutive whole-body Otub1 deletion in mice leads to perinatal lethality by asphyxiation. Analysis of (single-cell) RNA sequencing and proteome data demonstrated that OTUB1 is expressed in all lung cell types with a particularly high expression during late-stage lung development (E16.5, E18.5). At E18.5, the lungs of animals with Otub1 deletion presented with increased cell proliferation that decreased saccular air space and prevented inhalation. Flow cytometry-based analysis of E18.5 lung tissue revealed that Otub1 deletion increased proliferation of major lung parenchymal and mesenchymal/other non-hematopoietic cell types. Adult mice with conditional whole-body Otub1 deletion (wbOtub1
    MeSH term(s) Animals ; Cell Proliferation ; Cysteine Endopeptidases/physiology ; Female ; Homeostasis ; Hyperventilation/etiology ; Hyperventilation/pathology ; Lung Diseases/etiology ; Lung Diseases/metabolism ; Lung Diseases/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Respiratory Insufficiency/etiology ; Respiratory Insufficiency/pathology ; TOR Serine-Threonine Kinases/genetics ; TOR Serine-Threonine Kinases/metabolism
    Chemical Substances mTOR protein, mouse (EC 2.7.1.1) ; TOR Serine-Threonine Kinases (EC 2.7.11.1) ; Cysteine Endopeptidases (EC 3.4.22.-) ; Otub1 protein, mouse (EC 3.4.22.-)
    Language English
    Publishing date 2021-11-18
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639186-2
    ISSN 1530-6860 ; 0892-6638
    ISSN (online) 1530-6860
    ISSN 0892-6638
    DOI 10.1096/fj.202100346R
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2266: 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)
    Zs.MO 296: Show issues

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  3. Article ; Online: Rapid Identification of SARS-CoV-2 Variants of Concern Using a Portable

    Bechtold, Philippe / Wagner, Philipp / Hosch, Salome / Siegrist, Denise / Ruiz-Serrano, Amalia / Gregorini, Michele / Mpina, Maxmillian / Ondó, Florentino Abaga / Obama, Justino / Ayekaba, Mitoha Ondo'o / Engler, Olivier / Stark, Wendelin J / Daubenberger, Claudia A / Schindler, Tobias

    Analytical chemistry

    2021  Volume 93, Issue 49, Page(s) 16350–16359

    Abstract: The need for tools that facilitate rapid detection and continuous monitoring of SARS-CoV-2 variants of concern (VOCs) is greater than ever, as these variants are more transmissible and therefore increase the pressure of COVID-19 on healthcare systems. To ...

    Abstract The need for tools that facilitate rapid detection and continuous monitoring of SARS-CoV-2 variants of concern (VOCs) is greater than ever, as these variants are more transmissible and therefore increase the pressure of COVID-19 on healthcare systems. To address this demand, we aimed at developing and evaluating a robust and fast diagnostic approach for the identification of SARS-CoV-2 VOC-associated spike gene mutations. Our diagnostic assays detect the E484K and N501Y single-nucleotide polymorphisms (SNPs) as well as a spike gene deletion (HV69/70) and can be run on standard laboratory equipment or on the portable rapid diagnostic technology platform
    MeSH term(s) COVID-19/epidemiology ; COVID-19/virology ; COVID-19 Nucleic Acid Testing ; Equatorial Guinea/epidemiology ; Gene Deletion ; Humans ; Mutation ; Polymorphism, Single Nucleotide ; SARS-CoV-2/classification
    Language English
    Publishing date 2021-12-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1508-8
    ISSN 1520-6882 ; 0003-2700
    ISSN (online) 1520-6882
    ISSN 0003-2700
    DOI 10.1021/acs.analchem.1c02368
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4033: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: The functional interplay between the HIF pathway and the ubiquitin system - more than a one-way road.

    Günter, Julia / Ruiz-Serrano, Amalia / Pickel, Christina / Wenger, Roland H / Scholz, Carsten C

    Experimental cell research

    2017  Volume 356, Issue 2, Page(s) 152–159

    Abstract: The hypoxia inducible factor (HIF) pathway and the ubiquitin system represent major cellular processes that are involved in the regulation of a plethora of cellular signaling pathways and tissue functions. The ubiquitin system controls the ubiquitination ...

    Abstract The hypoxia inducible factor (HIF) pathway and the ubiquitin system represent major cellular processes that are involved in the regulation of a plethora of cellular signaling pathways and tissue functions. The ubiquitin system controls the ubiquitination of proteins, which is the covalent linkage of one or several ubiquitin molecules to specific targets. This ubiquitination is catalyzed by approximately 1000 different E3 ubiquitin ligases and can lead to different effects, depending on the type of internal ubiquitin chain linkage. The best-studied function is the targeting of proteins for proteasomal degradation. The activity of E3 ligases is antagonized by proteins called deubiquitinases (or deubiquitinating enzymes), which negatively regulate ubiquitin chains. This is performed in most cases by the catalytic removal of these chains from the targeted protein. The HIF pathway is regulated in an oxygen-dependent manner by oxygen-sensing hydroxylases. Covalent modification of HIFα subunits leads to the recruitment of an E3 ligase complex via the von Hippel-Lindau (VHL) protein and the subsequent polyubiquitination and proteasomal degradation of HIFα subunits, demonstrating the regulation of the HIF pathway by the ubiquitin system. This unidirectional effect of an E3 ligase on the HIF pathway is the best-studied example for the interplay between these two important cellular processes. However, additional regulatory mechanisms of the HIF pathway through the ubiquitin system are emerging and, more recently, also the reciprocal regulation of the ubiquitin system through components of the HIF pathway. Understanding these mechanisms and their relevance for the activity of each other is of major importance for the comprehensive elucidation of the oxygen-dependent regulation of cellular processes. This review describes the current knowledge of the functional bidirectional interplay between the HIF pathway and the ubiquitin system on the protein level.
    MeSH term(s) Animals ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Oxygen/metabolism ; Tumor Suppressor Proteins/metabolism ; Ubiquitin/metabolism ; Ubiquitin-Protein Ligases/metabolism
    Chemical Substances Basic Helix-Loop-Helix Transcription Factors ; Hypoxia-Inducible Factor 1, alpha Subunit ; Tumor Suppressor Proteins ; Ubiquitin ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; Oxygen (S88TT14065)
    Language English
    Publishing date 2017-07-15
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1493-x
    ISSN 1090-2422 ; 0014-4827
    ISSN (online) 1090-2422
    ISSN 0014-4827
    DOI 10.1016/j.yexcr.2017.03.027
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 563: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (1.OG)
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  5. Article: Rapid Identification of SARS-CoV-2 Variants of Concern Using a Portable peakPCR Platform

    Bechtold, Philippe / Wagner, Philipp / Hosch, Salome / Siegrist, Denise / Ruiz-Serrano, Amalia / Gregorini, Michele / Mpina, Maxmillian / Ondó, Florentino Abaga / Obama, Justino / Ayekaba, Mitoha Ondo’o / Engler, Olivier / Stark, Wendelin J. / Daubenberger, Claudia A. / Schindler, Tobias

    Analytical chemistry. 2021 Dec. 01, v. 93, no. 49

    2021  

    Abstract: The need for tools that facilitate rapid detection and continuous monitoring of SARS-CoV-2 variants of concern (VOCs) is greater than ever, as these variants are more transmissible and therefore increase the pressure of COVID-19 on healthcare systems. To ...

    Abstract The need for tools that facilitate rapid detection and continuous monitoring of SARS-CoV-2 variants of concern (VOCs) is greater than ever, as these variants are more transmissible and therefore increase the pressure of COVID-19 on healthcare systems. To address this demand, we aimed at developing and evaluating a robust and fast diagnostic approach for the identification of SARS-CoV-2 VOC-associated spike gene mutations. Our diagnostic assays detect the E484K and N501Y single-nucleotide polymorphisms (SNPs) as well as a spike gene deletion (HV69/70) and can be run on standard laboratory equipment or on the portable rapid diagnostic technology platform peakPCR. The assays achieved excellent diagnostic performance when tested with RNA extracted from culture-derived SARS-CoV-2 VOC lineages and clinical samples collected in Equatorial Guinea, Central-West Africa. Simplicity of usage and the relatively low cost are advantages that make our approach well suitable for decentralized and rapid testing, especially in resource-limited settings.
    Keywords COVID-19 infection ; RNA ; Severe acute respiratory syndrome coronavirus 2 ; analytical chemistry ; gene deletion ; genes ; health services ; laboratory equipment ; rapid methods ; Equatorial Guinea
    Language English
    Dates of publication 2021-1201
    Size p. 16350-16359.
    Publishing place American Chemical Society
    Document type Article
    ZDB-ID 1508-8
    ISSN 1520-6882 ; 0003-2700
    ISSN (online) 1520-6882
    ISSN 0003-2700
    DOI 10.1021/acs.analchem.1c02368
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Bonn / Germany

    Z 4' 52/94: Show issues
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  6. Article ; Online: Oxygen-dependent bond formation with FIH regulates the activity of the client protein OTUB1.

    Pickel, Christina / Günter, Julia / Ruiz-Serrano, Amalia / Spielmann, Patrick / Fabrizio, Jacqueline-Alba / Wolski, Witold / Peet, Daniel J / Wenger, Roland H / Scholz, Carsten C

    Redox biology

    2019  Volume 26, Page(s) 101265

    Abstract: Protein:protein interactions are the basis of molecular communication and are usually of transient non-covalent nature, while covalent interactions other than ubiquitination are rare. For cellular adaptations, the cellular oxygen and peroxide sensor ... ...

    Abstract Protein:protein interactions are the basis of molecular communication and are usually of transient non-covalent nature, while covalent interactions other than ubiquitination are rare. For cellular adaptations, the cellular oxygen and peroxide sensor factor inhibiting HIF (FIH) confers oxygen and oxidant stress sensitivity to the hypoxia inducible factor (HIF) by asparagine hydroxylation. We investigated whether FIH contributes to hypoxia adaptation also through other mechanisms and identified a hypoxia sensitive, likely covalent, bond formation by FIH with several client proteins, including the deubiquitinase ovarian tumor domain containing ubiquitin aldehyde binding protein 1 (OTUB1). Biochemical analyses were consistent with a co-translational amide bond formation between FIH and OTUB1, occurring within mammalian and bacterial cells but not between separately purified proteins. Bond formation is catalysed by FIH and highly dependent on oxygen availability in the cellular microenvironment. Within cells, a heterotrimeric complex is formed, consisting of two FIH and one covalently linked OTUB1. Complexation of OTUB1 by FIH regulates OTUB1 deubiquitinase activity. Our findings reveal an alternative mechanism for hypoxia adaptation with remarkably high oxygen sensitivity, mediated through covalent protein-protein interactions catalysed by an asparagine modifying dioxygenase.
    MeSH term(s) Cell Line, Tumor ; Cysteine Endopeptidases/genetics ; Cysteine Endopeptidases/metabolism ; Humans ; Hypoxia-Inducible Factor 1/metabolism ; Mass Spectrometry ; Oxidation-Reduction ; Oxygen/chemistry ; Oxygen/metabolism
    Chemical Substances Hypoxia-Inducible Factor 1 ; Cysteine Endopeptidases (EC 3.4.22.-) ; OTUB1 protein, human (EC 3.4.22.-) ; Oxygen (S88TT14065)
    Language English
    Publishing date 2019-07-02
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2701011-9
    ISSN 2213-2317 ; 2213-2317
    ISSN (online) 2213-2317
    ISSN 2213-2317
    DOI 10.1016/j.redox.2019.101265
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Rapid identification of Sars-CoV-2 variants of concern using the portable peakPCR platform

    Hosch, Salome / Bechtold, Philippe / Wagner, Philipp / Ruiz-Serrano, Amalia / Gregorini, Michele / Siegrist, Denise / Engler, Olivier / Stark, Wendelin J. / Daubenberger, Claudia A. / Schindler, Tobias

    medRxiv

    Abstract: The need for tools which allow rapid detection and continuous monitoring of Sars-CoV-2 variants of concern (VOC) is greater than ever, as these variants are more transmissible and therefore increase the pressure of COVID-19 on healthcare systems. To ... ...

    Abstract The need for tools which allow rapid detection and continuous monitoring of Sars-CoV-2 variants of concern (VOC) is greater than ever, as these variants are more transmissible and therefore increase the pressure of COVID-19 on healthcare systems. To address this demand, we aimed to develop and evaluate a robust and fast diagnostic approach for identification of Sars-CoV-2 VOC-associated spike gene mutations. Our diagnostic assays detect the E484K and N501Y SNPs as well as a spike gene deletion (HV69/70) and can be run on standard laboratory equipment or on the portable rapid diagnostic technology platform peakPCR. The assays achieved excellent diagnostic performance when tested with RNA extracted from culture-derived Sars-CoV-2 VOC lineages. Simplicity of usage and the relatively low costs are advantages which make our approach well-suited for decentralized and rapid testing, especially in resource limited settings.
    Keywords covid19
    Language English
    Publishing date 2021-05-21
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2021.05.21.21256124
    Database COVID19

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