title: ELL targets c-Myc for proteasomal degradation and suppresses tumour growth.
abstract: Increasing evidence supports that ELL (eleven-nineteen lysine-rich leukaemia) is a key regulator of transcriptional elongation, but the physiological function of Ell in mammals remains elusive. Here we show that ELL functions as an E3 ubiquitin ligase and targets c-Myc for proteasomal degradation. In addition, we identify that UbcH8 serves as a ubiquitin-conjugating enzyme in this pathway. Cysteine 595 of ELL is an active site of the enzyme; its mutation to alanine (C595A) renders the protein unable to promote the ubiquitination and degradation of c-Myc. ELL-mediated c-Myc degradation inhibits c-Myc-dependent transcriptional activity and cell proliferation, and also suppresses c-Myc-dependent xenograft tumour growth. In contrast, the ELL(C595A) mutant not only loses the ability to inhibit cell proliferation and xenograft tumour growth, but also promotes tumour metastasis. Thus, our work reveals a previously unrecognized function for ELL as an E3 ubiquitin ligase for c-Myc and a potential tumour suppressor.
authors.affiliation: The Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, 430072 Wuhan, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: The Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, 430072 Wuhan, China.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhou
authors.affiliation: The Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, 430072 Wuhan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ji
authors.affiliation: The Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, 430072 Wuhan, China.
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Mei
authors.affiliation: The Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, 430072 Wuhan, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
authors.affiliation: The Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, 430072 Wuhan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, 430072 Wuhan, China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, 430072 Wuhan, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: The Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, 430072 Wuhan, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.affiliation: The Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, 430072 Wuhan, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Ouyang
authors.affiliation: The Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, 430072 Wuhan, China.
authors.forename: Jiangang
authors.initials: J
authors.lastname: Zhou
authors.affiliation: The Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, 430072 Wuhan, China.|State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, 430072 Wuhan, China.
authors.forename: Wuhan
authors.initials: W
authors.lastname: Xiao
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D045325:HCT116 Cells; D057809:HEK293 Cells; D006801:Humans; D008239:Lysine / Q000378:metabolism; D008297:Male; D008819:Mice, Nude; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011485:Protein Binding; D059748:Proteolysis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D014158:Transcription, Genetic; D035602:Transcriptional Elongation Factors / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: C090862:ELL protein, human; D016271:Proto-Oncogene Proteins c-myc; D035602:Transcriptional Elongation Factors; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex; D008239:Lysine