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SHR Neuro Cancer Cardio Lipid Metab Microb

Putker, M; Madl, T; Vos, HR; de Ruiter, H; Visscher, M; van den Berg, MC; Kaplan, M; Korswagen, HC; Boelens, R; Vermeulen, M; Burgering, BM; Dansen, TB.
Redox-dependent control of FOXO/DAF-16 by transportin-1.
Mol Cell. 2013; 49(4): 730-742. Doi: 10.1016/j.molcel.2012.12.014 [OPEN ACCESS]
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Co-authors Med Uni Graz: Madl Tobias
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Abstract:: Forkhead box O (FOXO; DAF-16 in worms) transcription factors, which are of vital importance in cell-cycle control, stress resistance, tumor suppression, and organismal lifespan, are largely regulated through nucleo-cytoplasmic shuttling. Insulin signaling keeps FOXO/DAF-16 cytoplasmic, and hence transcriptionally inactive. Conversely, as in loss of insulin signaling, reactive oxygen species (ROS) can activate FOXO/DAF-16 through nuclear accumulation. How ROS regulate the nuclear translocation of FOXO/DAF-16 is largely unknown. Cysteine oxidation can stabilize protein-protein interactions through the formation of disulfide-bridges when cells encounter ROS. Using a proteome-wide screen that identifies ROS-induced mixed disulfide-dependent complexes, we discovered several interaction partners of FOXO4, one of which is the nuclear import receptor transportin-1. We show that disulfide formation with transportin-1 is required for nuclear localization and the activation of FOXO4/DAF-16 induced by ROS, but not by the loss of insulin signaling. This molecular mechanism for nuclear shuttling is conserved in C. elegans and directly connects redox signaling to the longevity protein FOXO/DAF-16. Copyright © 2013 Elsevier Inc. All rights reserved.
Find related publications in this database (using NLM MeSH Indexing): Active Transport, Cell Nucleus -; Amino Acid Sequence -; Amino Acid Substitution -; Animals -; Caenorhabditis elegans - cytology Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - metabolism; Cell Nucleus - metabolism; Cystine - metabolism; HEK293 Cells -; Humans -; Molecular Sequence Data -; Mutagenesis, Site-Directed -; Oxidation-Reduction -; Protein Binding -; Reactive Oxygen Species - metabolism; Transcription Factors - genetics Transcription Factors - metabolism; beta Karyopherins - metabolism beta Karyopherins - physiology