SUMOylation Attenuates Human {beta}-arrestin 2 Inhibition of IL-1R-TRAF6 Signaling [Gene Regulation]

November 25th, 2014 by Xiao, N., Li, H., Mei, W., Cheng, J.

β-arrestin 2 as an adaptor plays a role in the regulation of receptors desensitization, trafficking, and signaling. Bovine β-arrestin 2 has been shown to be SUMOylated on lysine 400 residue, which link it to the endocytosis of 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, which can reverse the SUMOylation of β-arrestin 2-mediated processes. Our study reveals SUMOylation as a novel mechanism in regulation of β-arrestin 2-mediated IL-1R-TRAF6 signaling.