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  1. Article ; Online: Ubiquitinomics: History, methods, and applications in basic research and drug discovery.

    Steger, Martin / Karayel, Özge / Demichev, Vadim

    Proteomics

    2022  Volume 22, Issue 15-16, Page(s) e2200074

    Abstract: The ubiquitin-proteasome system (UPS) was discovered about 40 years ago and is known to regulate a multitude of cellular processes including protein homeostasis. Ubiquitylated proteins are recognized by downstream effectors, resulting in alterations of ... ...

    Abstract The ubiquitin-proteasome system (UPS) was discovered about 40 years ago and is known to regulate a multitude of cellular processes including protein homeostasis. Ubiquitylated proteins are recognized by downstream effectors, resulting in alterations of protein abundance, activity, or localization. Not surprisingly, the ubiquitylation machinery is dysregulated in numerous diseases, including cancers and neurodegeneration. Mass spectrometry (MS)-based proteomics has emerged as a transformative technology for characterizing protein ubiquitylation in an unbiased fashion. Here, we provide an overview of the different MS-based approaches for studying protein ubiquitylation. We review various methods for enriching and quantifying ubiquitin modifications at the peptide or protein level, outline MS acquisition, and data processing approaches and discuss key challenges. Finally, we examine how MS-based ubiquitinomics can aid both basic biology and drug discovery research.
    MeSH term(s) Drug Discovery ; Proteasome Endopeptidase Complex/metabolism ; Proteomics/methods ; Ubiquitin/metabolism ; Ubiquitination
    Chemical Substances Ubiquitin ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
    Language English
    Publishing date 2022-05-11
    Publishing country Germany
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2032093-0
    ISSN 1615-9861 ; 1615-9853
    ISSN (online) 1615-9861
    ISSN 1615-9853
    DOI 10.1002/pmic.202200074
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Book: Wassernutzung in Vorder- und Mittelasien

    Steger, Martin

    Geschichte, Entwicklung und Probleme des Nahen Ostens und des Industieflandes

    2013  

    Author's details Martin Steger
    Language German
    Size 96 S, Ill., graph. Darst., Kt.
    Publisher Diplomica Verl
    Publishing place Hamburg
    Document type Book
    ISBN 3842891857 ; 9783842891852
    Database Former special subject collection: coastal and deep sea fishing

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  3. Book ; Online: Zur Verselbstständigung von Unionsagenturen

    Steger, Martin A

    Eine Untersuchung am Beispiel der Energie-Agentur ACER und ihrer Mitwirkung beim Erlass tertiären Unionsrechts

    (Veröffentlichungen des Instituts für Energierecht an der Universität zu Köln ; 183)

    2015  

    Abstract: Im Jahr 2011 hat die Agentur für die Zusammenarbeit der Energieregulierungsbehörden, kurz ACER, ihre Arbeit aufgenommen. Mangels Vorgaben im europäischen Primärrecht ist bis heute unklar, wie das Verhältnis einer Agentur zu den Mitgliedsstaaten und den ... ...

    Author's details Martin A. Steger
    Series title Veröffentlichungen des Instituts für Energierecht an der Universität zu Köln ; 183
    Abstract Im Jahr 2011 hat die Agentur für die Zusammenarbeit der Energieregulierungsbehörden, kurz ACER, ihre Arbeit aufgenommen. Mangels Vorgaben im europäischen Primärrecht ist bis heute unklar, wie das Verhältnis einer Agentur zu den Mitgliedsstaaten und den Unionsorganen auszugestalten ist. Es besteht Klärungsbedarf, was Kontrolle und Legitimation angeht. Dies gilt besonders für ACER. Als Vorform einer europäischen Regulierungsbehörde verfügt sie über gewichtige Befugnisse. Die Agentur ist unter anderem am Erlass von verbindlichem tertiären Unionsrecht in Form der sogenannten Netzkodizes beteiligt
    Language German
    Size Online-Ressource
    Edition 1. Aufl
    Publisher Nomos
    Publishing place Baden-Baden
    Document type Book ; Online
    Note Description based upon print version of record
    ISBN 9783845261324 ; 9783848719891 ; 3845261323 ; 3848719894
    DOI 10.5771/9783845261324
    Database Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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  4. Book ; Thesis: Zur Verselbstständigung von Unionsagenturen

    Steger, Martin A

    eine Untersuchung am Beispiel der Energie-Agentur ACER und ihrer Mitwirkung beim Erlass tertiären Unionsrechts

    (Veröffentlichungen des Instituts für Energierecht an der Universität zu Köln ; 183)

    2015  

    Institution Agency for the Cooperation of Energy Regulators
    Author's details Martin A. Steger
    Series title Veröffentlichungen des Instituts für Energierecht an der Universität zu Köln ; 183
    Keywords Unabhängigkeit ; Europäische Integration ; Agentur ; Europäische Union
    Language German
    Size 694 S.
    Edition 1. Aufl.
    Publisher Nomos
    Publishing place Baden-Baden
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Univ., Diss.--Köln, 2014
    ISBN 3848719894 ; 9783845261324 ; 9783848719891 ; 3845261323
    Database Former special subject collection: coastal and deep sea fishing

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  5. Article ; Online: Correction: CB

    Trazzi, Stefania / Steger, Martin / Mitrugno, Valentina Maria / Bartesaghi, Renata / Ciani, Elisabetta

    The Journal of biological chemistry

    2020  Volume 295, Issue 10, Page(s) 3388

    Language English
    Publishing date 2020-03-04
    Publishing country United States
    Document type Journal Article ; Published Erratum
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1074/jbc.AAC120.013006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Leucine-973 is a crucial residue differentiating insulin and IGF-1 receptor signaling.

    Nagao, Hirofumi / Cai, Weikang / Brandão, Bruna B / Wewer Albrechtsen, Nicolai J / Steger, Martin / Gattu, Arijeet K / Pan, Hui / Dreyfuss, Jonathan M / Wunderlich, F Thomas / Mann, Matthias / Kahn, C Ronald

    The Journal of clinical investigation

    2023  Volume 133, Issue 4

    Abstract: Insulin and IGF-1 receptors (IR and IGF1R) are highly homologous and share similar signaling systems, but each has a unique physiological role, with IR primarily regulating metabolic homeostasis and IGF1R regulating mitogenic control and growth. Here, we ...

    Abstract Insulin and IGF-1 receptors (IR and IGF1R) are highly homologous and share similar signaling systems, but each has a unique physiological role, with IR primarily regulating metabolic homeostasis and IGF1R regulating mitogenic control and growth. Here, we show that replacement of a single amino acid at position 973, just distal to the NPEY motif in the intracellular juxtamembrane region, from leucine, which is highly conserved in IRs, to phenylalanine, the highly conserved homologous residue in IGF1Rs, resulted in decreased IRS-1/PI3K/Akt/mTORC1 signaling and increased Shc/Gab1/MAPK cell cycle signaling. As a result, cells expressing L973F-IR exhibited decreased insulin-induced glucose uptake, increased cell growth, and impaired receptor internalization. Mice with knockin of the L973F-IR showed similar alterations in signaling in vivo, and this led to decreased insulin sensitivity, a modest increase in growth, and decreased weight gain when mice were challenged with a high-fat diet. Thus, leucine-973 in the juxtamembrane region of the IR acts as a crucial residue differentiating IR signaling from IGF1R signaling.
    MeSH term(s) Animals ; Mice ; Insulin/metabolism ; Insulin Receptor Substrate Proteins/genetics ; Insulin Receptor Substrate Proteins/metabolism ; Insulin-Like Growth Factor I/metabolism ; Insulin-Like Growth Factor I/pharmacology ; Leucine/genetics ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphoproteins/metabolism ; Phosphorylation ; Receptor, IGF Type 1/genetics ; Receptor, IGF Type 1/metabolism ; Receptor, Insulin/genetics ; Receptor, Insulin/metabolism ; Signal Transduction/genetics ; Humans
    Chemical Substances Insulin ; Insulin Receptor Substrate Proteins ; Insulin-Like Growth Factor I (67763-96-6) ; Leucine (GMW67QNF9C) ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Phosphoproteins ; Receptor, IGF Type 1 (EC 2.7.10.1) ; Receptor, Insulin (EC 2.7.10.1)
    Language English
    Publishing date 2023-02-15
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI161472
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Time-resolved in vivo ubiquitinome profiling by DIA-MS reveals USP7 targets on a proteome-wide scale.

    Steger, Martin / Demichev, Vadim / Backman, Mattias / Ohmayer, Uli / Ihmor, Phillip / Müller, Stefan / Ralser, Markus / Daub, Henrik

    Nature communications

    2021  Volume 12, Issue 1, Page(s) 5399

    Abstract: Mass spectrometry (MS)-based ubiquitinomics provides system-level understanding of ubiquitin signaling. Here we present a scalable workflow for deep and precise in vivo ubiquitinome profiling, coupling an improved sample preparation protocol with data- ... ...

    Abstract Mass spectrometry (MS)-based ubiquitinomics provides system-level understanding of ubiquitin signaling. Here we present a scalable workflow for deep and precise in vivo ubiquitinome profiling, coupling an improved sample preparation protocol with data-independent acquisition (DIA)-MS and neural network-based data processing specifically optimized for ubiquitinomics. Compared to data-dependent acquisition (DDA), our method more than triples identification numbers to 70,000 ubiquitinated peptides in single MS runs, while significantly improving robustness and quantification precision. Upon inhibition of the oncology target USP7, we simultaneously record ubiquitination and consequent changes in abundance of more than 8,000 proteins at high temporal resolution. While ubiquitination of hundreds of proteins increases within minutes of USP7 inhibition, we find that only a small fraction of those are ever degraded, thereby dissecting the scope of USP7 action. Our method enables rapid mode-of-action profiling of candidate drugs targeting DUBs or ubiquitin ligases at high precision and throughput.
    MeSH term(s) Cell Line, Tumor ; HCT116 Cells ; Humans ; Jurkat Cells ; Neural Networks, Computer ; Proteome/metabolism ; Proteomics/methods ; Signal Transduction ; Substrate Specificity ; Tandem Mass Spectrometry/methods ; Time Factors ; Ubiquitin/metabolism ; Ubiquitin-Specific Peptidase 7/metabolism ; Ubiquitination
    Chemical Substances Proteome ; Ubiquitin ; USP7 protein, human (EC 3.4.19.12) ; Ubiquitin-Specific Peptidase 7 (EC 3.4.19.12)
    Language English
    Publishing date 2021-09-13
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-021-25454-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Prolyl isomerization: a new PIN code for DSB repair.

    Sartori, Alessandro A / Steger, Martin

    Cell cycle (Georgetown, Tex.)

    2013  Volume 12, Issue 17, Page(s) 2717–2718

    MeSH term(s) DNA/genetics ; DNA End-Joining Repair ; Humans ; Peptidylprolyl Isomerase/genetics ; Peptidylprolyl Isomerase/metabolism
    Chemical Substances DNA (9007-49-2) ; Peptidylprolyl Isomerase (EC 5.2.1.8)
    Language English
    Publishing date 2013-08-19
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 2146183-1
    ISSN 1551-4005 ; 1538-4101 ; 1554-8627
    ISSN (online) 1551-4005
    ISSN 1538-4101 ; 1554-8627
    DOI 10.4161/cc.26077
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: The tumor suppressor kinase DAPK3 drives tumor-intrinsic immunity through the STING-IFN-β pathway.

    Takahashi, Mariko / Lio, Chan-Wang J / Campeau, Anaamika / Steger, Martin / Ay, Ferhat / Mann, Matthias / Gonzalez, David J / Jain, Mohit / Sharma, Sonia

    Nature immunology

    2021  Volume 22, Issue 4, Page(s) 485–496

    Abstract: Evasion of host immunity is a hallmark of cancer; however, mechanisms linking oncogenic mutations and immune escape are incompletely understood. Through loss-of-function screening of 1,001 tumor suppressor genes, we identified death-associated protein ... ...

    Abstract Evasion of host immunity is a hallmark of cancer; however, mechanisms linking oncogenic mutations and immune escape are incompletely understood. Through loss-of-function screening of 1,001 tumor suppressor genes, we identified death-associated protein kinase 3 (DAPK3) as a previously unrecognized driver of anti-tumor immunity through the stimulator of interferon genes (STING) pathway of cytosolic DNA sensing. Loss of DAPK3 expression or kinase activity impaired STING activation and interferon (IFN)-β-stimulated gene induction. DAPK3 deficiency in IFN-β-producing tumors drove rapid growth and reduced infiltration of CD103
    MeSH term(s) Animals ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Cell Line, Tumor ; Death-Associated Protein Kinases/genetics ; Death-Associated Protein Kinases/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Human Umbilical Vein Endothelial Cells/enzymology ; Human Umbilical Vein Endothelial Cells/metabolism ; Humans ; Immune Checkpoint Inhibitors/pharmacology ; Immunity, Innate/drug effects ; Interferon-beta/genetics ; Interferon-beta/metabolism ; LIM Domain Proteins/genetics ; LIM Domain Proteins/metabolism ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Mice, Inbred C57BL ; Mice, Knockout ; Neoplasms/drug therapy ; Neoplasms/enzymology ; Neoplasms/genetics ; Neoplasms/immunology ; Phosphorylation ; Signal Transduction ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Tumor Escape/drug effects ; Ubiquitination ; Mice
    Chemical Substances Immune Checkpoint Inhibitors ; LIM Domain Proteins ; LMO7 protein, human ; Lmo7 protein, mouse ; Membrane Proteins ; STING1 protein, human ; Sting1 protein, mouse ; Transcription Factors ; Interferon-beta (77238-31-4) ; DAPK3 protein, human (EC 2.7.11.1) ; Dapk3 protein, mouse (EC 2.7.11.1) ; Death-Associated Protein Kinases (EC 2.7.11.1)
    Language English
    Publishing date 2021-03-25
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2016987-5
    ISSN 1529-2916 ; 1529-2908
    ISSN (online) 1529-2916
    ISSN 1529-2908
    DOI 10.1038/s41590-021-00896-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.MG 42: Show issues

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  10. Article ; Online: Robust dimethyl-based multiplex-DIA doubles single-cell proteome depth via a reference channel.

    Thielert, Marvin / Itang, Ericka Cm / Ammar, Constantin / Rosenberger, Florian A / Bludau, Isabell / Schweizer, Lisa / Nordmann, Thierry M / Skowronek, Patricia / Wahle, Maria / Zeng, Wen-Feng / Zhou, Xie-Xuan / Brunner, Andreas-David / Richter, Sabrina / Levesque, Mitchell P / Theis, Fabian J / Steger, Martin / Mann, Matthias

    Molecular systems biology

    2023  Volume 19, Issue 9, Page(s) e11503

    Abstract: Single-cell proteomics aims to characterize biological function and heterogeneity at the level of proteins in an unbiased manner. It is currently limited in proteomic depth, throughput, and robustness, which we address here by a streamlined multiplexed ... ...

    Abstract Single-cell proteomics aims to characterize biological function and heterogeneity at the level of proteins in an unbiased manner. It is currently limited in proteomic depth, throughput, and robustness, which we address here by a streamlined multiplexed workflow using data-independent acquisition (mDIA). We demonstrate automated and complete dimethyl labeling of bulk or single-cell samples, without losing proteomic depth. Lys-N digestion enables five-plex quantification at MS1 and MS2 level. Because the multiplexed channels are quantitatively isolated from each other, mDIA accommodates a reference channel that does not interfere with the target channels. Our algorithm RefQuant takes advantage of this and confidently quantifies twice as many proteins per single cell compared to our previous work (Brunner et al, PMID 35226415), while our workflow currently allows routine analysis of 80 single cells per day. Finally, we combined mDIA with spatial proteomics to increase the throughput of Deep Visual Proteomics seven-fold for microdissection and four-fold for MS analysis. Applying this to primary cutaneous melanoma, we discovered proteomic signatures of cells within distinct tumor microenvironments, showcasing its potential for precision oncology.
    MeSH term(s) Humans ; Proteome ; Melanoma ; Proteomics ; Precision Medicine ; Skin Neoplasms ; Tumor Microenvironment
    Chemical Substances Proteome
    Language English
    Publishing date 2023-08-21
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2193510-5
    ISSN 1744-4292 ; 1744-4292
    ISSN (online) 1744-4292
    ISSN 1744-4292
    DOI 10.15252/msb.202211503
    Database MEDical Literature Analysis and Retrieval System OnLINE

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