Publication Date:
2011-07-19
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3251012/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3251012/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉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 -- Nimer, Stephen D -- GM62437/GM/NIGMS NIH HHS/ -- R01 GM062437/GM/NIGMS NIH HHS/ -- R01 GM062437-12/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2011 Aug 5;333(6043):765-9. doi: 10.1126/science.1201662. Epub 2011 Jul 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Pharmacology and Chemistry Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21764752" target="_blank"〉PubMed〈/a〉
Keywords:
Acetylation
;
Animals
;
Cell Line
;
Cell Line, Tumor
;
*Cell Transformation, Neoplastic
;
Core Binding Factor Alpha 2 Subunit/chemistry/*metabolism
;
E1A-Associated p300 Protein/antagonists & inhibitors/*metabolism
;
Fetal Blood/cytology
;
Gene Expression Profiling
;
Hematopoietic Stem Cells/*cytology/physiology
;
Humans
;
Leukemia, Myeloid, Acute/*metabolism/pathology
;
Lysine/*metabolism
;
Mice
;
Mice, Inbred C57BL
;
Mutant Proteins/metabolism
;
Oncogene Proteins, Fusion/chemistry/*metabolism
;
Preleukemia/metabolism/pathology
;
Protein Binding
;
Protein Interaction Domains and Motifs
;
Protein Processing, Post-Translational
;
Transcriptional Activation
;
Tumor Cells, Cultured
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
