Regulation of interleukin-10 receptor ubiquitination and stability by beta-TrCP-containing ubiquitin E3 ligase.
Interleukin-10 (IL-10) initiates potent anti-inflammatory effects via activating its cell surface receptor, composed of IL-10R1 and IL-10R2 subunits. The level of IL-10R1 is a major determinant of the cells' responsiveness to IL-10. Here, via a series of biochemical analyses using 293T cells reconstituted with IL-10R1, we identify the latter as ... a novel substrate of βTrCP-containing ubiquitin E3 ligase. Within the intracellular tail of IL-10R1, a canonical ((318)DpSGFGpS) and a slightly deviated ((369)DpSGICLQEP) βTrCP recognition motif can additively recruit βTrCP in a phosphorylation-dependent manner. βTrCP recruitment leads to ubiquitination, endocytosis and degradation of IL-10R1, subsequently reducing the cellular responsiveness to IL-10. Our study uncovers a novel negative regulatory mechanism that may potentially affect IL-10 function in target cells under physiological or pathological conditions.
Mesh Terms:
Cell Line, Humans, Interleukin-10, Interleukin-10 Receptor alpha Subunit, Interleukin-10 Receptor beta Subunit, Phosphorylation, Protein Stability, Protein Transport, Receptors, Interleukin-10, Ubiquitin-Protein Ligases, Ubiquitination, beta-Transducin Repeat-Containing Proteins
Cell Line, Humans, Interleukin-10, Interleukin-10 Receptor alpha Subunit, Interleukin-10 Receptor beta Subunit, Phosphorylation, Protein Stability, Protein Transport, Receptors, Interleukin-10, Ubiquitin-Protein Ligases, Ubiquitination, beta-Transducin Repeat-Containing Proteins
PLoS ONE
Date: Nov. 17, 2011
PubMed ID: 22087322
View in: Pubmed Google Scholar
Download Curated Data For This Publication
135484
Switch View:
- Interactions 2
- PTM Genes 1