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Protein-protein-interaction network organization of the hypusine modification system - Zurich Open Repository and Archive


Sievert, H; Venz, S; Platas-Barradas, O; Dhople, V M; Schaletzky, M; Nagel, C H; Braig, M; Preukschas, M; Pällmann, N; Bokemeyer, C; Brümmendorf, T H; Pörtner, R; Walther, R; Duncan, K E; Hauber, J; Balabanov, S (2012). Protein-protein-interaction network organization of the hypusine modification system. Molecular & Cellular Proteomics, 11(11):1289-1305.

Abstract

Hypusine modification of eukaryotic initiation factor 5A (eIF-5A) represents a unique and highly specific post-translational modification with regulatory functions in cancer, diabetes, and infectious diseases. However, the specific cellular pathways that are influenced by the hypusine modification remain largely unknown. To globally characterize eIF-5A and hypusine-dependent pathways, we used an approach that combines large-scale bioreactor cell culture with tandem affinity purification and mass spectrometry: "bioreactor-TAP-MS/MS." By applying this approach systematically to all four components of the hypusine modification system (eIF-5A1, eIF-5A2, DHS, and DOHH), we identified 248 interacting proteins as components of the cellular hypusine network, with diverse functions including regulation of translation, mRNA processing, DNA replication, and cell cycle regulation. Network analysis of this data set enabled us to provide a comprehensive overview of the protein-protein interaction landscape of the hypusine modification system. In addition, we validated the interaction of eIF-5A with some of the newly identified associated proteins in more detail. Our analysis has revealed numerous novel interactions, and thus provides a valuable resource for understanding how this crucial homeostatic signaling pathway affects different cellular functions.

Abstract

Hypusine modification of eukaryotic initiation factor 5A (eIF-5A) represents a unique and highly specific post-translational modification with regulatory functions in cancer, diabetes, and infectious diseases. However, the specific cellular pathways that are influenced by the hypusine modification remain largely unknown. To globally characterize eIF-5A and hypusine-dependent pathways, we used an approach that combines large-scale bioreactor cell culture with tandem affinity purification and mass spectrometry: "bioreactor-TAP-MS/MS." By applying this approach systematically to all four components of the hypusine modification system (eIF-5A1, eIF-5A2, DHS, and DOHH), we identified 248 interacting proteins as components of the cellular hypusine network, with diverse functions including regulation of translation, mRNA processing, DNA replication, and cell cycle regulation. Network analysis of this data set enabled us to provide a comprehensive overview of the protein-protein interaction landscape of the hypusine modification system. In addition, we validated the interaction of eIF-5A with some of the newly identified associated proteins in more detail. Our analysis has revealed numerous novel interactions, and thus provides a valuable resource for understanding how this crucial homeostatic signaling pathway affects different cellular functions.

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6 citations in Web of Science®
7 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Hematology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:November 2012
Deposited On:19 Feb 2013 17:30
Last Modified:05 Apr 2016 16:30
Publisher:American Society for Biochemistry and Molecular Biology
ISSN:1535-9476
Additional Information:This research was originally published in: Sievert, H; Venz, S; Platas-Barradas, O; Dhople, V M; Schaletzky , M; Nagel, C H; Braig, M; Preukschas, M; Pällmann, N; Bokemeyer, C; Brümmendorf, T H; Pörtner, R; Walther, R; Duncan, K E; Hauber, J; Balabanov, S (2012). Protein-protein-interaction network organization of the hypusine modification system. Molecular & Cellular Proteomics, 11(11):1289-1305. © the American Society for Biochemistry and Molecular Biology.
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1074/mcp.M112.019059
PubMed ID:22888148

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