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| THE T(8-21)-FUSION PROTEIN INTERFERES WITH AML-1B-DEPENDENT TRANSCRIPTIONAL ACTIVATION |
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| Author(s): MEYERS S, LENNY N, HIEBERT SW |
| Source: MOLECULAR AND CELLULAR BIOLOGY Volume: 15 Issue: 4 Pages: 1974-1982 Published: APR 1995 |
| Times Cited: 307 References: 46 |
| Abstract: The AML-1/CBF beta transcription factor complex is targeted by both the t(8;21) and the inv(16) chromosomal alterations, which are frequently observed in acute myelogenous leukemia. AML-1 is a site-specific DNA-binding protein that recognizes the enhancer core motif TGTGGT. The t(8;21) translocation fuses the first 177 amino acids of AML-1 to MTG8 (also known as ETO), generating a chimeric protein that retains the DNA-binding domain of AML-1. Analysis of endogenous AML-1 DNA-binding complexes suggested the presence of at least two AML-1 isoforms. Accordingly, we screened a human B-cell cDNA library and isolated a larger, potentially alternatively spliced, form of AML1, termed AML1B. AML-1B is a protein of 53 kDa that binds to a consensus AML-1-binding site and complexes with CBF beta. Subcellular fractionation experiments demonstrated that both AML-1 and AML-1/ETO are efficiently extracted from the nucleus under ionic conditions but that AML-1B is localized to a salt-resistant nuclear compartment. Analysis of the transcriptional activities of AML-1, AML-1B, and AML-1/ETO demonstrated that only AML-1B activates transcription from the T-cell receptor beta enhancer, Mixing experiments indicated that AML-1/ETO can efficiently block AML-1B-dependent transcriptional activation, suggesting that the t(8;21) translocation creates a dominant interfering protein. |
| Document Type: Article |
| Language: English |
Addresses:
1. ST JUDE CHILDRENS HOSP, DEPT TUMOR CELL BIOL, MEMPHIS, TN 38105 USA |
| Publisher: AMER SOC MICROBIOLOGY, 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: QM492 |
| ISSN: 0270-7306 |
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