Negative regulation of granulocytic differentiation in the myeloid precursor cell line 32Dc13 by ear-2, a mammalian homolog of Drosophila seven-up, and a chimeric leukemogenic gene, AML1/ETO(MTG8)

Mee Young Ahn, Gang Huang, Suk Chul Bae, Hee Jun Wee, Woo Young Kim, Yoshiaki Ito

Resultado de la investigación: Articlerevisión exhaustiva

80 Citas (Scopus)

Resumen

The polyomavirus enhancer binding protein 2αB (AML1/PEBP2αB/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 PEBP2αB interacting protein, Ear-2, an orphan member of the nuclear hormone receptor superfamily that directly binds to and can inhibit the function of PEBP2αB. 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 PEBP2αB and Ear-2 appears to determine the choice between growth or differentiation for myeloid cells.

Idioma originalEnglish (US)
Páginas (desde-hasta)1812-1817
Número de páginas6
PublicaciónProceedings of the National Academy of Sciences of the United States of America
Volumen95
N.º4
DOI
EstadoPublished - feb. 17 1998
Publicado de forma externa

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