HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 19, 19512-19522, May 7, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/19/19512    most recent M309074200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cho, J.-Y. Articles by Libermann, T. A. Search for Related Content PubMed PubMed Citation Articles by Cho, J.-Y. Articles by Libermann, T. A. Social Bookmarking                      What's this?

Isoforms of the Ets Transcription Factor NERF/ELF-2 Physically Interact with AML1 and Mediate Opposing Effects on AML1-mediated Transcription of the B Cell-specific blk Gene^*

Je-Yoel Cho, Yasmin Akbarali, Luiz F. Zerbini, Xuesong Gu, Jay Boltax, Yihong Wang, Peter Oettgen, Dong-Er Zhang¶, and Towia A. Libermann||

From the BIDMC Genomics Center and the New England Baptist Bone and Joint Institute, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston, Massachusetts 02115 and the ^¶Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, California 92037

We previously isolated different isoforms of a new Ets transcription factor family member, NERF/ELF-2, NERF-2, NERF-1a, and NERF-1b. In contrast to the inhibitory isoforms NERF-1a and NERF-1b, NERF-2 acts as a transactivator of the B cell-specific blk promoter. We now report that NERF-2 and NERF-1 physically interact with AML1 (RUNX1), a frequent target for chromosomal translocations in leukemia. NERF-2 bound to AML1 via an interaction site located in a basic region upstream of the Ets domain. This is in contrast to most other Ets factors such as Ets-1 that bind to AML1 via the Ets domain, suggesting that different Ets factors utilize different domains for interaction with AML1. The interaction between AML1 and NERF-2 led to cooperative transactivation of the blk promoter, whereas the interaction between AML1 and NERF-1a led to repression of AML1-mediated transactivation. To delineate the differences in function of the different NERF isoforms, we determined that the transactivation domain of NERF-2 is encoded by the N-terminal 100 amino acids, which have been replaced in NERF-1a by a 19-amino acid transcriptionally inactive sequence. Furthermore, acidic domains A and B, which are conserved in NERF-2 and the related proteins ELF-1 and MEF/ELF-4, but not in NERF-1a, are largely responsible for NERF-2-mediated transactivation. Because translocation of the Ets factor Tel to AML1 is a frequent event in childhood pre-B leukemia, understanding the interaction of Ets factors with AML1 in the context of a B cell-specific promoter might help to determine the function of Ets factors and AML1 in leukemia.

Received for publication, August 15, 2003 , and in revised form, January 20, 2004.

^* This work was supported by National Institutes of Health Grants PO1 CA72009 (to T. A. L. and D.-E. Z.) and RO1 CA76323 (to T. A. L.). 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.

Present address: Dept. of Oral Biochemistry, School of Dentistry, Kyungpook National University, Daegu, 700-422 Korea.

^|| To whom correspondence should be addressed: Beth Israel Deaconess Medical Center, 4 Blackfan Circle, Boston, MA 02115. Tel.: 617-667-3393; Fax: 617-975-5299; E-mail: tliberma{at}bidmc.harvard.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				L. Rainis, T. Toki, J. E. Pimanda, E. Rosenthal, K. Machol, S. Strehl, B. Gottgens, E. Ito, and S. Izraeli The Proto-Oncogene ERG in Megakaryoblastic Leukemias Cancer Res., September 1, 2005; 65(17): 7596 - 7602. [Abstract] [Full Text] [PDF]