A TFIID-SAGA Perturbation that Targets MYB and Suppresses Acute Myeloid Leukemia

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)

URL: https://www.ncbi.nlm.nih.gov/pubmed/29316427
DOI: 10.1016/j.ccell.2017.12.002

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 labs > Vakoc lab
CSHL Cancer Center Program > Gene Regulation and Cell Proliferation
Depositing User: Matt Covey
Date: 8 January 2018
Date Deposited: 10 Jan 2018 20:51
Last Modified: 12 Jun 2018 19:26
PMCID: PMC5764110
Related URLs:
URI: http://repository.cshl.edu/id/eprint/35795

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