title: Lymphocyte signaling: regulation of FoxO transcription factors by microRNAs.
abstract: The Forkhead box O (FoxO) family of transcription factors is important for the maintenance of immunological homeostasis and tolerance by controlling the development and function of B and T lymphocytes. Because dysregulation in FoxO activity can result in chronic inflammation and autoimmunity, the transcriptional activity of FoxO proteins is tightly controlled and generally dependent on complex posttranslational modifications that lead either to their nuclear entry and subsequent activation or, alternatively, to their nuclear export. The phosphatidylinositol 3-kinase (PI3K)-protein kinase B (PKB/Akt) axis represents the major pathway phosphorylating and thereby inactivating FoxO proteins. However, recent results have revealed an additional posttranscriptional mechanism of FoxO inactivation by microRNAs. The discovery of this molecular pathway may provide a new therapeutic avenue for the modulation of FoxO activity in immune-mediated diseases using either microRNA targeting antagomirs or synthetic microRNA mimics, a topic that is addressed in this review.
authors.affiliation: Deutsches Rheuma-Forschungszentrum Berlin, Berlin, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Haftmann
authors.forename: Anna-Barbara
authors.initials: AB
authors.lastname: Stittrich
authors.forename: Evridiki
authors.initials: E
authors.lastname: Sgouroudis
authors.forename: Mareen
authors.initials: M
authors.lastname: Matz
authors.forename: Hyun-Dong
authors.initials: HD
authors.lastname: Chang
authors.forename: Andreas
authors.initials: A
authors.lastname: Radbruch
authors.forename: Mir-Farzin
authors.initials: MF
authors.lastname: Mashreghi
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics; D000818:Animals; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D015398:Signal Transduction
chemical_list: D051858:Forkhead Transcription Factors; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt