Nuclear receptor corepressor (CoR)-histone deacetylase (HDAC) complex recruitment is indispensable for the biological activities of the retinoic acid receptor fusion proteins of acute promyelocytic leukemias. We report here that ETO (eight-twenty-one or MTG8), which is fused to the acute myelogenous leukemia 1 (AML1) transcription factor in t(8;21) AML, interacts via its zinc finger region with a conserved domain of the corepressors N-CoR and SMRT and recruits HDAC in vivo. The fusion protein AML1-ETO retains the ability of ETO to form stable complexes with N-CoR/SMRT and HDAC. Deletion of the ETO C terminus abolishes CoR binding and HDAC recruitment and severely impairs the ability of AML1-ETO to inhibit differentiation of hematopoietic precursors. These data indicate that formation of a stable complex with CoR- HDAC is crucial to the activation of the leukemogenic potential of AML1 by ETO and suggest that aberrant recruitment of corepressor complexes is a general mechanism of leukemogenesis.
|Titolo:||Aberrant recruitment of the nuclear receptor corepressor-histone deacetylase complex by the acute myeloid leukemia fusion partner ETO|
PELICCI, PIER GIUSEPPE (Penultimo)
|Parole Chiave:||Hematopoietic Stem Cells; Histone Deacetylases; DNA-Binding Proteins; Humans; Cell Differentiation; Recombinant Fusion Proteins; Chromosomes, Human, Pair 8; Leukemia, Myeloid; Protein Binding; Models, Biological; Nuclear Receptor Co-Repressor 1; Receptors, Retinoic Acid; Proto-Oncogene Proteins; Tumor Cells, Cultured; Transcription Factors; Nuclear Proteins; Chromosomes, Human, Pair 21; Repressor Proteins; Core Binding Factor Alpha 2 Subunit|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Data di pubblicazione:||dic-1998|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1128/MCB.18.12.7185|
|Appare nelle tipologie:||01 - Articolo su periodico|