TitleThe ETO protein disrupted in t(8;21)-associated acute myeloid leukemia is a corepressor for the promyelocytic leukemia zinc finger protein.
Publication TypeJournal Article
Year of Publication2000
AuthorsMelnick, A M., Westendorf J J., Polinger A, Carlile G W., Arai S, Ball H J., Lutterbach B, Hiebert S W., and Licht J D.
JournalMol Cell Biol
Volume20
Issue6
Pagination2075-86
Date Published2000 Mar
ISSN0270-7306
KeywordsAcute Disease, Animals, Chromosomes, Human, Pair 21, Chromosomes, Human, Pair 8, COS Cells, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Humans, Kruppel-Like Transcription Factors, Leukemia, Myeloid, Promyelocytic Leukemia Zinc Finger Protein, Proto-Oncogene Proteins, RUNX1 Translocation Partner 1 Protein, Transcription Factors, Transfection, Translocation, Genetic, Zinc Fingers
Abstract

<p>The ETO protein was originally identified by its fusion to the AML-1 transcription factor in translocation (8;21) associated with the M2 form of acute myeloid leukemia (AML). The resulting AML-1-ETO fusion is an aberrant transcriptional regulator due to the ability of ETO, which does not bind DNA itself, to recruit the transcriptional corepressors N-CoR, SMRT, and Sin3A and histone deacetylases. The promyelocytic leukemia zinc finger (PLZF) protein is a sequence-specific DNA-binding transcriptional factor fused to retinoic acid receptor alpha in acute promyelocytic leukemia associated with the (11;17)(q23;q21) translocation. PLZF also mediates transcriptional repression through the actions of corepressors and histone deacetylases. We found that ETO is one of the corepressors recruited by PLZF. The PLZF and ETO proteins associate in vivo and in vitro, and ETO can potentiate transcriptional repression by PLZF. The N-terminal portion of ETO forms complexes with PLZF, while the C-terminal region, which was shown to bind to N-CoR and SMRT, is required for the ability of ETO to augment transcriptional repression by PLZF. The second repression domain (RD2) of PLZF, not the POZ/BTB domain, is necessary to bind to ETO. Corepression by ETO was completely abrogated by histone deacetylase inhibitors. This identifies ETO as a cofactor for a sequence-specific transcription factor and indicates that, like other corepressors, it functions through the action of histone deactylase.</p>

DOI10.1128/MCB.20.6.2075-2086.2000
Alternate JournalMol Cell Biol
PubMed ID10688654
PubMed Central IDPMC110824
Grant ListR01 CA059936 / CA / NCI NIH HHS / United States
CA 59936 / CA / NCI NIH HHS / United States
CA 64140 / CA / NCI NIH HHS / United States
F32 CA077167 / CA / NCI NIH HHS / United States
K08 CA73762 / CA / NCI NIH HHS / United States
R01 CA064140 / CA / NCI NIH HHS / United States