title: Regulation of interleukin-10 receptor ubiquitination and stability by beta-TrCP-containing ubiquitin E3 ligase.
abstract: 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.
authors.affiliation: MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University, Nanjing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Jiang
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.forename: Liang
authors.initials: L
authors.lastname: Yuan
authors.forename: Jianghuai
authors.initials: J
authors.lastname: Liu
mesh_terms: D002460:Cell Line; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology; D053709:Interleukin-10 Receptor alpha Subunit; D053710:Interleukin-10 Receptor beta Subunit; D010766:Phosphorylation; D055550:Protein Stability; D021381:Protein Transport; D053701:Receptors, Interleukin-10 / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination; D044844:beta-Transducin Repeat-Containing Proteins / Q000378:metabolism*
chemical_list: D053709:Interleukin-10 Receptor alpha Subunit; D053710:Interleukin-10 Receptor beta Subunit; D053701:Receptors, Interleukin-10; D044844:beta-Transducin Repeat-Containing Proteins; D016753:Interleukin-10; D044767:Ubiquitin-Protein Ligases
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