title: Nedd8 targets ubiquitin ligase Smurf2 for neddylation and promote its degradation.
abstract: E3 ubiquitin ligases are pivotal effectors of the ubiquitin-proteasome system as they determine the substrate specificity and transfer ubiquitin to the substrate. HECT-type ubiquitin ligase Smad ubiquitination regulatory factor 2 (Smurf2) has been demonstrated functions as a tumor suppressor. However, the mechanisms underlying regulation of Smurf2 is still unclear. Here we show that ubiquitin-like protein Nedd8 targets the HECT-type ubiquitin ligase Smurf2 for neddylation, and promotes Smurf2 degradation. Neddylation of Smurf1 activates its ubiquitin ligase activity and Smurf2 exerts Nedd8 ligase activity. This study provided new clues of Smurf2 activation regulation.
authors.affiliation: Department of Cell Biology, Anhui Medical University, Hefei, Anhui Province 230032, China; State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Shu
authors.affiliation: Department of Cell Biology, Anhui Medical University, Hefei, Anhui Province 230032, China; State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Rongfei
authors.initials: R
authors.lastname: Wei
authors.affiliation: Dept Biochem & Mol Biol, Capital Medical University, No. 1 Dongjiaominxiang, Dongcheng District, Beijing 100730, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Shan
authors.initials: S
authors.lastname: He
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China. Electronic address: zhanglq@nic.bmi.ac.cn.
authors.forename: Lingqiang
authors.initials: L
authors.lastname: Zhang
mesh_terms: D004789:Enzyme Activation; D057809:HEK293 Cells; D006801:Humans; D000075687:NEDD8 Protein; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination / Q000502:physiology*; D014452:Ubiquitins / Q000378:metabolism*
chemical_list: D000075687:NEDD8 Protein; C082860:NEDD8 protein, human; D014452:Ubiquitins; C471641:SMURF2 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: Nedd8; Protein neddylation; Protein ubiquitination; Smurf2; Ubiquitin ligase