ETO, a Target of t(8;21) in Acute Leukemia, Interacts with the N-CoR and mSin3 Corepressors
Year: 1998
Type: article
Abstract: t(8;21) is one of the most frequent translocations associated with acute myeloid leukemia. It produces a chimeric protein, acute myeloid leukemia-1 (AML-1)-eight-twenty-one (ETO), that contains the amino-terminal DNA binding domain of the AML-1 transcriptional regulator fused to nearly all of ETO. Here we demonstrate that ETO interacts with the nuclear receptor corepressor N-CoR, the mSin3 corepressors, and histone deacetylases. Endogenous ETO also cosediments on sucrose gradients with mSin3A, N-CoR, and histone deacetylases, suggesting that it is a component of one or more corepressor complexes. Deletion mutagenesis indicates that ETO interacts with mSin3A independently of its association with N-CoR. Single amino acid mutations that impair the ability of ETO to interact with the central portion of N-CoR affect the ability of the t(8;21) fusion protein to repress transcription. Finally, AML-1/ETO associates with histone deacetylase activity and a histone deacetylase inhibitor impairs the ability of the fusion protein to repress transcription. Thus, t(8;21) fuses a component of a corepressor complex to AML-1 to repress transcription.
Source: Molecular and Cellular Biology
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1554689623, MOLECULAR BASIS OF ACTION OF THE PUTATIVE ONCOGENE BCL6, E2F AND DIFFERENTIATION, APOPTOSIS, AND LEUKEMIA, T (12/21) FUSION PROTEIN AND LEUKEMOGENESIS, G4513176822, Mechanisms of Transcriptional Repressors and Co-repressors, Role of TEL and the t(12;21) in B cell ALL, G5853943267, Role of AML1-ETO in Acute Leukemia, G9000081609, Cancer Center Support Grant
OpenAlex ID: W2125668148