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Originally published In Press as doi:10.1074/jbc.M407239200 on September 17, 2004

J. Biol. Chem., Vol. 279, Issue 47, 49281-49288, November 19, 2004
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The Nuclear Receptor Co-repressor (N-CoR) Utilizes Repression Domains I and III for Interaction and Co-repression with ETO*

Jörn Lausen, Seongeun Cho, Shaohua Liu, and Milton H. Werner, Distinguished Young Scholar of the W. M. Keck Foundation{ddagger}

From the Laboratory of Molecular Biophysics, The Rockefeller University, New York, New York 10021

The acute human leukemias are associated with the presence of chimeric gene products that arise from spontaneous chromosomal translocations. The t(8;21) translocation gene product led to the discovery of the Eight Twenty-One (ETO) gene. When fused to RUNX1, ETO is thought to mediate the formation of a repressive complex at RUNX1-dependent genes. ETO has also been found to act as a co-repressor of the promyelocytic zinc finger and Bcl-6 oncoproteins, suggesting that it may play a common role as a transcriptional co-repressor leading to human disease. An analysis of ETO-mediated repression revealed that one of the key binding partners of ETO is the nuclear receptor co-repressor (N-CoR). It is shown that two highly conserved domains of ETO interact with repression domains I and III of N-CoR. One of the ETO domains displays significant homology to Drosophila TAFII110, whereas the other is a predicted zinc binding motif that engages a conserved PPLXP motif in repression domain III of N-CoR. Together, these domains of ETO cooperate in repression with N-CoR and the binding sites in N-CoR overlap with those for other repressive factors. Thus, ETO has the potential to participate in a number of repressive complexes, which can be distinguished by their binding partners and target genes.


Received for publication, June 28, 2004 , and in revised form, September 8, 2004.

* This work was supported in part by a fellowship from the Deutsche Forschungsgemeinschaft (LA 1389/1-1) (to J. L.) and by the Specialized Center for Research Grant from the Leukemia and Lymphoma Society (to M. H. W.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

{ddagger} To whom correspondence should be addressed: The Rockefeller University, 1230 York Ave., Box 42, New York, 10021 NY. Tel.: 212-327-7221; Fax: 212-327-7222; E-mail: mwerner{at}portugal.rockefeller.edu.


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