FBXO3 Protein Promotes Ubiquitylation and Transcriptional Activity of AIRE (Autoimmune Regulator)
| Autor: | Wei Shao, Kristina Zumer, Koh Fujinaga, B. Matija Peterlin |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Positive Transcriptional Elongation Factor B Transcription Genetic Medical and Health Sciences Biochemistry P-TEFb Mice 0302 clinical medicine Transcription (biology) Protein phosphorylation Phosphorylation transcription factor Regulation of gene expression autoimmunity Biological Sciences Autoimmune regulator Ubiquitin ligase 030220 oncology & carcinogenesis Transcription Biochemistry & Molecular Biology 1.1 Normal biological development and functioning Biology Autoimmune Disease FBXO3 03 medical and health sciences Genetic Protein Domains AIRE Underpinning research Genetics Animals Humans Gene Regulation ubiquitylation Molecular Biology Transcription factor SKP Cullin F-Box Protein Ligases F-Box Proteins Ubiquitination Cell Biology Molecular biology protein phosphorylation 030104 developmental biology HEK293 Cells Chemical Sciences biology.protein gene regulation Transcription Factors |
| Zdroj: | The Journal of biological chemistry, vol 291, iss 34 Journal of Biological Chemistry |
| ISSN: | 1083-351X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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