title: Post-translational modification networks regulating FOXP3 function.
abstract: Forkhead box (FOX)P3 is a requisite transcription factor for the development and maintenance of immunosuppressive function of regulatory T (Treg) cells, and therefore for immune homeostasis. Post-translational modifications (PTMs) can transiently alter the functionality of transcription factors, and recent evidence reveals that FOXP3 can be regulated by various PTMs including acetylation, ubiquitination, and phosphorylation. Here, we review the current understanding of how these modifications control FOXP3, including regulation of DNA binding, transactivation potential, and proteasomal degradation. We place these findings in the context of the biology of Treg cells, and discuss both limitations in translating biochemical findings into in vivo functions and the opportunities presented by a better understanding of the molecular mechanisms that can transiently control FOXP3 activity in response to environmental cues.
authors.affiliation: Division of Pediatrics, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Cell Biology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Jorg
authors.initials: J
authors.lastname: van Loosdregt
authors.affiliation: Division of Pediatrics, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Cell Biology, University Medical Center Utrecht, Utrecht, The Netherlands; Memorial Sloan-Kettering Cancer Center, New York, NY, USA. Electronic address: p.j.coffer@umcutrecht.nl.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Coffer
mesh_terms: D000818:Animals; D060833:Cellular Microenvironment; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D007108:Immune Tolerance; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D015533:Transcriptional Activation
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D046988:Proteasome Endopeptidase Complex
keywords: Forkhead box P3; immune homeostasis; post-translational modifications; regulatory T cells