title: Redox regulation of FoxO transcription factors.
abstract: Transcription factors of the forkhead box, class O (FoxO) family are important regulators of the cellular stress response and promote the cellular antioxidant defense. On one hand, FoxOs stimulate the transcription of genes coding for antioxidant proteins located in different subcellular compartments, such as in mitochondria (i.e. superoxide dismutase-2, peroxiredoxins 3 and 5) and peroxisomes (catalase), as well as for antioxidant proteins found extracellularly in plasma (e.g., selenoprotein P and ceruloplasmin). On the other hand, reactive oxygen species (ROS) as well as other stressful stimuli that elicit the formation of ROS, may modulate FoxO activity at multiple levels, including posttranslational modifications of FoxOs (such as phosphorylation and acetylation), interaction with coregulators, alterations in FoxO subcellular localization, protein synthesis and stability. Moreover, transcriptional and posttranscriptional control of the expression of genes coding for FoxOs is sensitive to ROS. Here, we review these aspects of FoxO biology focusing on redox regulation of FoxO signaling, and with emphasis on the interplay between ROS and FoxOs under various physiological and pathophysiological conditions. Of particular interest are the dual role played by FoxOs in cancer development and their key role in whole body nutrient homeostasis, modulating metabolic adaptations and/or disturbances in response to low vs. high nutrient intake. Examples discussed here include calorie restriction and starvation as well as adipogenesis, obesity and type 2 diabetes.
authors.affiliation: Institute of Nutrition, Department of Nutrigenomics, Friedrich-Schiller-Universität Jena, Dornburger Straße 29, 07743 Jena, Germany. Electronic address: lars-oliver.klotz@uni-jena.de.
authors.forename: Lars-Oliver
authors.initials: LO
authors.lastname: Klotz
authors.affiliation: Instituto de Investigaciones Biomédicas "Alberto Sols" (CSIC-UAM), Arturo Duperier, 4, 28029 Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Sánchez-Ramos
authors.affiliation: Instituto de Investigaciones Biomédicas "Alberto Sols" (CSIC-UAM), Arturo Duperier, 4, 28029 Madrid, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Prieto-Arroyo
authors.affiliation: Institute of Nutrition, Department of Nutrigenomics, Friedrich-Schiller-Universität Jena, Dornburger Straße 29, 07743 Jena, Germany.
authors.forename: Pavel
authors.initials: P
authors.lastname: Urbánek
authors.affiliation: Institute of Nutrition, Department of Nutrigenomics, Friedrich-Schiller-Universität Jena, Dornburger Straße 29, 07743 Jena, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Steinbrenner
authors.affiliation: Instituto de Investigaciones Biomédicas "Alberto Sols" (CSIC-UAM), Arturo Duperier, 4, 28029 Madrid, Spain. Electronic address: mpmonsalve@iib.uam.es.
authors.forename: Maria
authors.initials: M
authors.lastname: Monsalve
mesh_terms: D000595:Amino Acid Sequence; D001798:Blood Proteins / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D001798:Blood Proteins; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D024101:Mitochondrial Proteins; D020033:Protein Isoforms; D017382:Reactive Oxygen Species
keywords: Akt; Antioxidant proteins; C. elegans; DAF-16; Forkhead box proteins; Insulin signaling; Oxidative stress; Stress signaling