title: SUMOylation attenuates human β-arrestin 2 inhibition of IL-1R/TRAF6 signaling.
abstract: 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.
authors.affiliation: From the Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, State Key Laboratory of Oncogenes and Related Genes in Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China and.
authors.forename: Ning
authors.initials: N
authors.lastname: Xiao
authors.affiliation: the Key Laboratory of Pediatric Hematology and Oncology, Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: From the Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, jymeiwh@shsmu.edu.cn.
authors.forename: Wenhan
authors.initials: W
authors.lastname: Mei
authors.affiliation: From the Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, State Key Laboratory of Oncogenes and Related Genes in Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China and jkcheng@shsmu.edu.cn.
authors.forename: Jinke
authors.initials: J
authors.lastname: Cheng
mesh_terms: D000818:Animals; D019390:Arrestins / Q000378:metabolism*; D004705:Endocytosis; D004797:Enzyme-Linked Immunosorbent Assay; D057809:HEK293 Cells; D006801:Humans; D008239:Lysine / Q000737:chemistry; D061986:MCF-7 Cells; D051379:Mice; D011485:Protein Binding; D017472:Receptors, Interleukin-1 / Q000378:metabolism*; D015398:Signal Transduction; D058207:Sumoylation; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins
chemical_list: C000605254:ARRB2 protein, human; C000605258:Arrb2 protein, mouse; D019390:Arrestins; D017472:Receptors, Interleukin-1; D048029:TNF Receptor-Associated Factor 6; D018808:Transcription Factor AP-1; D025801:Ubiquitin; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins; D008239:Lysine
keywords: Arrestin; Arrestin Cell Signaling; Cell Signaling; IL-1; Small Ubiquitin-like Modifier (SUMO); Ubiquitylation (Ubiquitination)