Global and context-specific transcriptional consequences of oncogenic Fbw7 mutations

Reviewer #3 (Public Review):

In this study, the authors aim to compare the effects of Fbw7 deletion (-/-) and Fbw7 mutation (R/+) on the transcriptional landscape. Since Fbw7 targets a number of transcription factors (TFs), including c-Myc and c-Jun, which are frequently deregulated in cancer, many downstream genes are expected to be affected in both cell lines. The authors thus examined transcriptional profiles as well as histone modifications and TF occupancy in WT, Fbw7(-/-), and Fbw7(R/+) cells. While the purpose of this study is interesting and important, the interpretation of the results is somewhat puzzling and complex. Furthermore, the details of the experimental design in some parts are not clearly described, which hinders the understanding and evaluation of this study. Overall, the biological impact of deletion or mutation of Fbw7 on cancer still remains unclear.


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