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PMID: 9465099 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 95 ·No. 4 ·1998-02-17 ·Pages 1812-7

Ahn MY, Huang G, Bae SC, Wee HJ, Kim WY, Ito Y

Abstract

The polyomavirus enhancer binding protein 2alphaB (AML1/PEBP2alphaB/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 PEBP2alphaB interacting protein, Ear-2, an orphan member of the nuclear hormone receptor superfamily that directly binds to and can inhibit the function of PEBP2alphaB. 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 PEBP2alphaB and Ear-2 appears to determine the choice between growth or differentiation for myeloid cells.

MeSH Terms

Animals Cell Differentiation Cell Division/drug effects Core Binding Factor Alpha 2 Subunit DNA-Binding Proteins/genetics Gene Expression Regulation Granulocyte Colony-Stimulating Factor/pharmacology Granulocytes/cytology Mice Protein Binding Proto-Oncogene Proteins RUNX1 Translocation Partner 1 Protein Receptors, Steroid/genetics Transcription Factors/genetics Transcription, Genetic

Chemicals

Core Binding Factor Alpha 2 Subunit DNA-Binding Proteins Proto-Oncogene Proteins RUNX1 Translocation Partner 1 Protein RUNX1T1 protein, human Receptors, Steroid Runx1 protein, mouse Transcription Factors Granulocyte Colony-Stimulating Factor

Authors & Affiliations

6 authors, click to expand affiliations / ORCID

Ahn M Y

Department of Viral Oncology, Institute for Virus Research, Kyoto University, Shogoin, Sakyo-ku, Kyoto 606, Japan.

Huang G

Bae S C

Wee H J

Kim W Y

Ito Y

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36 references, click to expand

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Article Info

Journal

Proceedings of the National Academy of Sciences of the United States of America

Abbr.

Proc Natl Acad Sci U S A

ISSN

0027-8424

DOI

10.1073/pnas.95.4.1812

Published

1998-02-17

Pages

1812-7

Language

English

Region

United States

NLM ID

7505876

PMCID

PMC19195

Subset

External Links

PubMed source DOI: 10.1073/pnas.95.4.1812 PMC Full Text View journal details

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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.

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