title: FBXO3 Protein Promotes Ubiquitylation and Transcriptional Activity of AIRE (Autoimmune Regulator).
abstract: The autoimmune regulator (AIRE) is a transcription factor which is expressed in medullary thymic epithelial cells. It directs the expression of otherwise tissue-specific antigens, which leads to the elimination of autoreactive T cells during development. AIRE is modified post-translationally by phosphorylation and ubiquitylation. In this report we connected these modifications. AIRE, which is phosphorylated on two specific residues near its N terminus, then binds to the F-box protein 3 (FBXO3) E3 ubiquitin ligase. In turn, this SCF(FBXO3) (SKP1-CUL1-F box) complex ubiquitylates AIRE, increases its binding to the positive transcription elongation factor b (P-TEFb), and potentiates its transcriptional activity. Because P-TEFb is required for the transition from initiation to elongation of transcription, this interaction ensures proper expression of AIRE-responsive tissue-specific antigens in the thymus.
authors.affiliation: From the Departments of Medicine, Microbiology, and Immunology, University of California, San Francisco, California 94143-07030703 and.
authors.forename: Wei
authors.initials: W
authors.lastname: Shao
authors.affiliation: Max-Planck-Institute for Biophysical Chemistry, Department of Molecular Biology, Am Fassberg 11, 37077 Göttingen, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Zumer
authors.affiliation: From the Departments of Medicine, Microbiology, and Immunology, University of California, San Francisco, California 94143-07030703 and.
authors.forename: Koh
authors.initials: K
authors.lastname: Fujinaga
authors.affiliation: From the Departments of Medicine, Microbiology, and Immunology, University of California, San Francisco, California 94143-07030703 and matija.peterlin@ucsf.edu.
authors.forename: B Matija
authors.initials: BM
authors.lastname: Peterlin
mesh_terms: D000818:Animals; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D010766:Phosphorylation / Q000502:physiology; D042925:Positive Transcriptional Elongation Factor B / Q000235:genetics / Q000378:metabolism; D000072417:Protein Domains; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*; D054875:Ubiquitination / Q000502:physiology*; D000096927:AIRE Protein
chemical_list: D044783:F-Box Proteins; D042925:Positive Transcriptional Elongation Factor B; D044843:SKP Cullin F-Box Protein Ligases; D014157:Transcription Factors; D000096927:AIRE Protein; C533903:FBXO3 protein, human
keywords: AIRE; FBXO3; P-TEFb; autoimmunity; gene regulation; protein phosphorylation; transcription factor; ubiquitylation (ubiquitination)