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Many ETS family transcription factors can recruit mutant p53, and interaction specificity patterns correlate with ETS gene expression changes in ovarian cancer

ABSTRACT: The tumor suppressor transcription factor p53 is mutated in nearly 50% of all cancer cases, and this frequency increases with stage and resistance to therapy. Hotspot p53 mutations lose direct DNA binding activity while gaining oncogenic function. These structural p53 mutants can bind to new regions of the genome via interactions with other transcription factors. One example is the ETS transcription factor ETS2, which was previously reported to bind mutant p53. Yet, a comprehensive understanding of mutant p53 association with the ETS family needs to be understood. Here, we compare mutant p53 interaction across 26 ETS transcription factors. Mutant p53 bound ETS proteins better than wild-type p53. All ETS proteins tested bound to mutant p53 to some extent, yet relative binding differed. The ETS DNA binding domain provided a common interaction interface, but strong binding required a second interaction domain. Genome-wide mapping found that the ETS protein ERG could recruit mutant p53 to regulatory regions of genes necessary for morphogenesis, locomotion, and androgen response in prostate cancer cells. Lastly, ETS factors that interact strongly with mutant p53 tend to be upregulated in p53 mutant ovarian cancer. These results suggest that multiple ETS proteins can work with mutant p53 in cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE270925 | GEO | 2024/06/28

REPOSITORIES: GEO

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Oncogenic ETS proteins replace activated Ras/MAPK signaling in prostate cells.

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