title: Itch promotes the neddylation of JunB and regulates JunB-dependent transcription.
abstract: Protein neddylation is essential for the viability of most organisms and is widely involved in the regulation of immunity, DNA damage and repair, cell signaling and cell cycle. Unlike RING-type neddylation ligases, HECT-type neddylation ligase remains less defined. Here, we show that Itch is a novel HECT-type neddylation E3 ligase and we identify JunB as a substrate of Nedd8 modification by Itch. JunB neddylation attenuates its transcriptional activity. In addition, JunB neddylation mediated by Itch promotes its ubiquitination-dependent degradation. Therefore, these findings define a new HECT-type neddylation ligase and its neddylation substrate.
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Collaborative Innovation Center for Cancer Medicine, Beijing 100850, China.
authors.forename: Haiwen
authors.initials: H
authors.lastname: Li
authors.affiliation: Beijing Institute of Basic Medical Sciences, Beijing 100850, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Zhu
authors.affiliation: The First Hospital Attached to Guiyang College of Traditional Chinese Medicine, Guiyang 550001, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Collaborative Innovation Center for Cancer Medicine, Beijing 100850, China.
authors.forename: Fuchu
authors.initials: F
authors.lastname: He
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Collaborative Innovation Center for Cancer Medicine, Beijing 100850, China; Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Capital Medical University, Beijing 100069, China. Electronic address: xpxp922@163.com.
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, Collaborative Innovation Center for Cancer Medicine, Beijing 100850, China; Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning Province, 116044, China. Electronic address: zhanglq@nic.bmi.ac.cn.
authors.forename: Lingqiang
authors.initials: L
authors.lastname: Zhang
mesh_terms: D055162:Biocatalysis; D045325:HCT116 Cells; D057809:HEK293 Cells; D006801:Humans; D000075687:NEDD8 Protein / Q000378:metabolism*; D011485:Protein Binding; D059748:Proteolysis; D012097:Repressor Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: C581727:JunB protein, human; D000075687:NEDD8 Protein; D012097:Repressor Proteins; D014157:Transcription Factors; D044763:Ubiquitin-Conjugating Enzymes; C432966:ITCH protein, human; D044767:Ubiquitin-Protein Ligases; C000596156:UBE2M protein, human
keywords: Itch; JunB; Neddylation ligase; Transcriptional activity