| Literature DB >> 33275876 |
Caixia Hou1, Abhisek Mandal1, Jürgen Rohr1, Oleg V Tsodikov2.
Abstract
ETS family transcription factors of ERG and FLI1 play a key role in oncogenesis of prostate cancer and Ewing sarcoma by binding regulatory DNA sites and interfering with function of other factors. Mithramycin (MTM) is an anti-cancer, DNA binding natural product that functions as a potent antagonist of ERG and FLI1 by an unknown mechanism. We present a series of crystal structures of the DNA binding domain (DBD) of ERG/FLI1 culminating in a structure of a high-order complex of the ERG/FLI1 DBD, transcription factor Runx2, core-binding factor beta (Cbfβ), and MTM on a DNA enhancer site, along with supporting DNA binding studies using MTM and its analogues. Taken together, these data provide insight into allosteric mechanisms underlying ERG and FLI1 transactions and their disruption by MTM analogues.Entities:
Keywords: cancer; crystal structure; natural product; protein-DNA binding; transcription
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Year: 2020 PMID： 33275876 PMCID： PMC8106648 DOI： 10.1016/j.str.2020.11.012
Source DB: PubMed Journal: Structure ISSN： 0969-2126 Impact factor: 5.006