SUMOylation attenuates human β-arrestin 2 inhibition of IL-1R/TRAF6 signaling.
β-Arrestin 2 as an adaptor plays a role in the regulation of receptor desensitization, trafficking, and signaling. Bovine β-arrestin 2 has been shown to be SUMOylated on the lysine 400 residue, which links it to the endocytosis of the β2-adrenergic receptor. Here we identify a major SUMOylation site, lysine 295, ... on human β-arrestin 2. SUMOylation on this site attenuates β-arrestin 2 binding to TRAF6, then enhances TRAF6 oligomerization and autoubiquitination, and consequently leads to the increase of TRAF6-mediated NF-κB/AP-1 activation. We further determine SENP1 as a specific de-SUMOylation protease that can reverse the SUMOylation of β-arrestin 2-mediated processes. Our study reveals SUMOylation as a novel mechanism in the regulation of β-arrestin 2-mediated IL-1R/TRAF6 signaling.
Mesh Terms:
Animals, Arrestins, Endocytosis, Enzyme-Linked Immunosorbent Assay, HEK293 Cells, Humans, Lysine, MCF-7 Cells, Mice, Protein Binding, Receptors, Interleukin-1, Signal Transduction, Sumoylation, TNF Receptor-Associated Factor 6, Transcription Factor AP-1, Ubiquitin
Animals, Arrestins, Endocytosis, Enzyme-Linked Immunosorbent Assay, HEK293 Cells, Humans, Lysine, MCF-7 Cells, Mice, Protein Binding, Receptors, Interleukin-1, Signal Transduction, Sumoylation, TNF Receptor-Associated Factor 6, Transcription Factor AP-1, Ubiquitin
J. Biol. Chem.
Date: Jan. 23, 2015
PubMed ID: 25425640
View in: Pubmed Google Scholar
Download Curated Data For This Publication
187454
Switch View:
- Interactions 3