1. ¹Program in Molecular and Cellular Biology, Tulane University, New Orleans, LA 70112, USA
2. ²Department of Pediatrics, Tulane University School of Medicine, New Orleans, LA 70112, USA
3. ³Department of Pediatrics, Program in Molecular and Cellular Biology, and the Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA 70112, USA

Correspondence: CS Hemenway, E-mail: chemenw@tulane.edu

⁴Current address: SL-37, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112, USA

⁵Current address: Dana Farber Cancer Institute, Boston, MA 02115, USA

Received 23 August 2002; Revised 12 December 2002; Accepted 13 December 2003.

Abstract

The mixed lineage leukemia (MLL) gene at chromosome band 11q23 is commonly involved in reciprocal translocations that are detected in acute leukemias. Evidence suggests that the resulting MLL fusion genes contribute to leukemogenesis. AF9 is a common MLL fusion partner in acute myeloid leukemia. The AF9 protein functions as a transcriptional activator in artificial reporter gene assays and a structurally related protein in yeast, ANC1/TFG3, is a component of the SWI/SNF complex. Apart from these observations, little is known about the biologic function of AF9 in mammals. We have found that a recently described transcriptional repressor, BCL-6 corepressor (BCoR), interacts with the carboxy-terminus of AF9. The interaction of AF9 with BCoR has been confirmed by independent in vitro and in vivo protein-binding studies. The BCoR gene is expressed as several alternatively spliced transcripts. AF9 only binds BCoR isoforms that contain a unique 34 aa sequence located in the mid-portion of the protein. In artificial reporter gene assays, a BCoR isoform that binds AF9 efficiently suppresses AF9 transcriptional activity, while a nonbinding isoform does not. These results indicate that different isoforms of BCoR have unique biologic properties and that cell function may be partly determined by the different isoforms that are present within the cell.