Xu, Y., Milazzo, J. P., Somerville, T. D. D., Tarumoto, Y., Huang, Y. H., Ostrander, E. L., Wilkinson, J. E., Challen, G. A., Vakoc, C. R. (January 2018) A TFIID-SAGA Perturbation that Targets MYB and Suppresses Acute Myeloid Leukemia. Cancer Cell, 33 (1). 13-28 e8. ISSN 1878-3686 (Electronic)1535-6108 (Linking)
Abstract
Targeting of general coactivators is an emerging strategy to interfere with oncogenic transcription factors (TFs). However, coactivator perturbations often lead to pleiotropic effects by influencing numerous TFs. Here we identify TAF12, a subunit of TFIID and SAGA coactivator complexes, as a selective requirement for acute myeloid leukemia (AML) progression. We trace this dependency to a direct interaction between the TAF12/TAF4 histone-fold heterodimer and the transactivation domain of MYB, a TF with established roles in leukemogenesis. Ectopic expression of the TAF4 histone-fold fragment can efficiently squelch TAF12 in cells, suppress MYB, and regress AML in mice. Our study reveals a strategy for potent MYB inhibition in AML and highlights how an oncogenic TF can be selectively neutralized by targeting a general coactivator complex.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | Myb Saga Taf12 Tfiid acute myeloid leukemia coactivator epigenetics |
| Subjects: | bioinformatics > genomics and proteomics > genetics & nucleic acid processing > epigenetics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > epigenetics diseases & disorders > cancer > cancer types > leukemia |
| CSHL Authors: | |
| Communities: | CSHL Cancer Center Program > Gene Regulation and Cell Proliferation CSHL labs > Vakoc lab CSHL Cancer Center Program > Cancer Genetics and Genomics Program |
| Depositing User: | Matt Covey |
| Date: | 8 January 2018 |
| Date Deposited: | 10 Jan 2018 20:51 |
| Last Modified: | 05 Nov 2020 17:11 |
| PMCID: | PMC5764110 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/35795 |
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