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The mixed lineage leukemia fusion partner AF9 binds specific isoforms of the BCL-6 corepressor

Oncogene volume 22, pages 3395–3406 (2003)Cite this article

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.

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Acknowledgements

This work was supported in part by National Institutes of Health Grant CA78318 and by developmental funds of the Tulane Cancer Center. We thank Roxanne Reger and the Tulane Center for Gene Therapy for technical assistance with digital deconvolution microscopy.

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Author notes

  1. R Sathish Srinivasan & Charles S Hemenway

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

  2. Andrea C de Erkenez

    Present address: Dana Farber Cancer Institute, Boston, MA, 02115, USA

Authors and Affiliations

  1. Program in Molecular and Cellular Biology, Tulane University, New Orleans, 70112, LA, USA

    R Sathish Srinivasan

  2. Department of Pediatrics, Tulane University School of Medicine, New Orleans, 70112, LA, USA

    Andrea C de Erkenez

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

    Charles S Hemenway

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  1. R Sathish Srinivasan
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Correspondence to Charles S Hemenway.

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Srinivasan, R., Erkenez, A. & Hemenway, C. The mixed lineage leukemia fusion partner AF9 binds specific isoforms of the BCL-6 corepressor. Oncogene 22, 3395–3406 (2003). https://doi.org/10.1038/sj.onc.1206361

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