ELL targets c-Myc for proteasomal degradation and suppresses tumour growth
| Autor: | Bo Hu, Zhichao Mei, Jing Wang, Chi Zhou, Gang Ouyang, Jiangang Zhou, Xing Liu, Wei Ji, Yu Chen, Dawei Zhang, Wuhan Xiao, Wei Zhang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Cell signaling Proteasome Endopeptidase Complex Transcription Genetic Ubiquitin-Protein Ligases Science Mutant General Physics and Astronomy Mice Nude General Biochemistry Genetics and Molecular Biology Article Proto-Oncogene Proteins c-myc 03 medical and health sciences Ubiquitin Calcium-binding protein Neoplasms Animals Humans Cell Proliferation Multidisciplinary biology Cell growth Lysine HEK 293 cells General Chemistry HCT116 Cells Molecular biology Xenograft Model Antitumor Assays Ubiquitin ligase Cell biology Rats 030104 developmental biology HEK293 Cells Proteasome Proteolysis biology.protein Transcriptional Elongation Factors Protein Binding |
| Zdroj: | Nature Communications, Vol 7, Iss 1, Pp 1-15 (2016) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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. The expression of the oncogene Myc is carefully controlled and dysregulation often leads to cancer. Here, the authors describe an E3 ligase for Myc—ELL—and show that it likely controls the ubiquitination and degradation of Myc. |
| Databáze: | OpenAIRE |
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