ELL targets c-Myc for proteasomal degradation and suppresses tumour growth
Authors: Yu Chen
Chi Zhou
Xing Liu
Jiangang Zhou
Bo Hu
Wei Zhang
Jing Wang
Wei Ji
Gang Ouyang
Zhichao Mei
Wuhan Xiao
Dawei Zhang
Journal: Nature Communications (2016)
Discipline: Multidisciplinary
Keywords: ELL; transcriptional elongation; E3 ubiquitin ligase; c-Myc; proteasomal degradation
Affiliations: 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.

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. 

Retracted: No

PubPeer comments:
 ![file] , 
 In this figure (Fig.7b), we intended to present representative figures for each experiment (pHAGE control and pHAGE-ELL). In order to keep balance with Fig.7e and Fig.7h, we intended to choose three figures for each. Therefore, we chose three figures from four original figures taken under a dissection microscope by the first author. However, when we chose the figures, due to our carelessness, we did not notice that two of them in each experiment were actually taken from one same field, which means only two representative figures can be presented here for each experiment. We think that this mistake does not affect the main conclusion draw from this figure. If it is needed, we can contact journal to delete one representative figure for each experiment. , 
 #2 Yes, I think it best that you contact the journal to discuss the authenticity of the data presented in this paper. Can the authors confirm that they (the first author or other authors) performed these experiments themselves, or did they use a third party? I ask because there are additional issues in Figure 7f. Similar areas are shown in red, slightly dissimilar areas are identified in yellow. I did not examine the rest of the data carefully. *** ![file] , 
 ![file] Same problem in Fig7e and h. , 
 After got these comments, we take them seriously. We re-checked all figures of this paper carefully. Besides these errors pointed out by the comments, we also find wrong markers in Fig.6d and Supplemental Fig.13E. We have contacted Journal and hope that we can make the changes soon. Again, these errors do not affect the main conclusions draw by these figures. we are still stood by our data. However, we also realize that these mistakes were not permitted by the scientific fields. Sorry for bring some confusions to the field due to carelessness. , 
 Here is the revised Fig.7 ![file] , 
 #6 Thank you for your reply. Would you be able to provide high resolution images of the micrographs that will remain in the paper? , 
 #7 The high resolution image is too big, I can not attach it at this window. Can I email it to you? , 
 Here are high resolution images! Hope it reaches you well. [file] , 
 #9 Thank you, that worked. , 
 #9 Now authors only counted colonies in only one view area, how did they get statistical significance and the error bar? , 
 Those are representative images, which are not the only images used for statictical analysis. ![file] ![file] ![file] , 
 This images seems to be taken from the same field too. ![file] Since there are problems with all those photos, can you share all the images used for the statistical analysis in order to allow data reproducibility and dispel doubts? , 
 We have contacted Journal to make corrections. Hopefully, we can resolve these concerns after correction. Please keep your eyes on it. ,