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Negative regulation of granulocytic differentiation in the myeloid precursor cell line 32Dcl3 by ear-2, a mammalian homolog of Drosophila seven-up, and a chimeric leukemogenic gene, AML1/ETO(MTG8)

Authors
Ahn MYHuang GBae SCWee HJKim WYIto Y
Issue Date
Feb-1998
Publisher
NATL ACAD SCIENCES
Citation
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.95, no.4, pp.1812 - 1817
Journal Title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume
95
Number
4
Start Page
1812
End Page
1817
URI
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/150346
DOI
10.1073/pnas.95.4.1812
ISSN
0027-8424
Abstract
The polyomavirus enhancer binding protein 2 alpha B (AML1/PEBP2 alpha B/Cbfa2) plays a pivotal role in granulocyte colony-stimulating factor (G-CSF)-mediated differentiation of a myeloid progenitor cell line, 32Dc13. In this article, we report the identification of a PEBP2 alpha B interacting protein, Ear-2. an orphan member of the nuclear hormone receptor superfamily that directly binds to and can inhibit the function of PEBP2 alpha B, Ear-2 is expressed in proliferating 32Dc13 cells in presence of interleukin 3 but is down-regulated during differentiation induced by G-CSF, Interestingly, AML1/ETO(MTG8), a leukemogenic chimeric protein can block the differentiation of 32Dc13 cells, which is accompanied by the sustained expression of ear-2. Overexpression of Ear-2 can prevent G-CSF-induced differentiation, strongly suggesting that ear-2 is a key negative regulator of granulocytic differentiation, Our results indicate that a dynamic balance existing between PEBP2 alpha B and Ear-2 appears to determine the choice between growth or differentiation for myeloid cells.
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