Protein-protein-interaction network organization of the hypusine modification system

Media type: E-Article

Title: Protein-protein-interaction network organization of the hypusine modification system

Contributor: Sievert, Henning [Author]; Venz, Simone [Author]; Platas Barradas, Oscar [Author]; Dhople, Vishnu M. [Author]; Schaletzky, Martin [Author]; Nagel, Claus-Henning [Author]; Balabanov, Melanie [Author]; Preukschas, Michael [Author]; Pällmann, Nora [Author]; Bokemeyer, Carsten [Author]; Brümmendorf, Tim Henrik [Author]; Pörtner, Ralf [Author]; Walther, Reinhard [Author]; Duncan, Kent E. [Author]; Hauber, Joachim [Author]; Balabanov, Stefan [Author]

Corporation: Technische Universität Hamburg-Harburg ; Technische Universität Hamburg-Harburg, Institut für Bioprozess- und Biosystemtechnik

Published: 2012

Language: English

DOI: 10.15480/882.1937; 10.1074%2Fmcp.M112.019059

Identifier:

Keywords: Animals ; Computational Biology ; DNA-Binding Proteins ; Humans ; Lysine ; Mass Spectrometry ; Mice ; Mixed Function Oxygenases ; Multivesicular Bodies ; NIH 3T3 Cells ; Nuclear Proteins ; Oxidoreductases Acting on CH-NH Group Donors ; Peptide Fragments ; Peptide Initiation Factors ; Protein Transport ; RNA-Binding Proteins ; Recombinant Fusion Proteins ; Reproducibility of Results ; Ribosomal Proteins ; Subcellular Fractions ; Protein Interaction Maps ; Protein Processing, Post-Translational

Origination:

Footnote:

Description: 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.

Access State: Open Access

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