| Title | The leukemogenicity of AML1-ETO is dependent on site-specific lysine acetylation. |
| Publication Type | Journal Article |
| Year of Publication | 2011 |
| Authors | Wang, Lan, Gural Alexander, Sun Xiao-Jian, Zhao Xinyang, Perna Fabiana, Huang Gang, Hatlen Megan A., Vu Ly, Liu Fan, Xu Haiming, Asai Takashi, Xu Hao, Deblasio Tony, Menendez Silvia, Voza Francesca, Jiang Yanwen, Cole Philip A., Zhang Jinsong, Melnick Ari, Roeder Robert G., and Nimer Stephen D. |
| Journal | Science |
| Volume | 333 |
| Issue | 6043 |
| Pagination | 765-9 |
| Date Published | 2011 Aug 05 |
| ISSN | 1095-9203 |
| Keywords | Acetylation, Animals, Cell Line, Cell Line, Tumor, Cell Transformation, Neoplastic, Core Binding Factor Alpha 2 Subunit, E1A-Associated p300 Protein, Fetal Blood, Gene Expression Profiling, Hematopoietic Stem Cells, Humans, Leukemia, Myeloid, Acute, Lysine, Mice, Mice, Inbred C57BL, Mutant Proteins, Oncogene Proteins, Fusion, Preleukemia, Protein Binding, Protein Interaction Domains and Motifs, Protein Processing, Post-Translational, RUNX1 Translocation Partner 1 Protein, Transcriptional Activation, Tumor Cells, Cultured |
| Abstract | <p>The chromosomal translocations found in acute myelogenous leukemia (AML) generate oncogenic fusion transcription factors with aberrant transcriptional regulatory properties. Although therapeutic targeting of most leukemia fusion proteins remains elusive, the posttranslational modifications that control their function could be targetable. We found that AML1-ETO, the fusion protein generated by the t(8;21) translocation, is acetylated by the transcriptional coactivator p300 in leukemia cells isolated from t(8;21) AML patients, and that this acetylation is essential for its self-renewal-promoting effects in human cord blood CD34(+) cells and its leukemogenicity in mouse models. Inhibition of p300 abrogates the acetylation of AML1-ETO and impairs its ability to promote leukemic transformation. Thus, lysine acetyltransferases represent a potential therapeutic target in AML.</p> |
| DOI | 10.1126/science.1201662 |
| Alternate Journal | Science |
| PubMed ID | 21764752 |
| PubMed Central ID | PMC3251012 |
| Grant List | R01 GM062437 / GM / NIGMS NIH HHS / United States R01 GM062437-12 / GM / NIGMS NIH HHS / United States R37 GM062437 / GM / NIGMS NIH HHS / United States GM62437 / GM / NIGMS NIH HHS / United States |