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  • Original Paper
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Interaction of AF4 wild-type and AF4·MLL fusion protein with SIAH proteins: indication for t(4;11) pathobiology?

Oncogene volume 23, pages 6237–6249 (2004)Cite this article

Abstract

The human AF4 (ALL-1 fused gene on chromosome 4) gene (4q11) is recurrently involved in reciprocal translocations to the MLL (mixed lineage leukemia) gene (11q23), correlated with high-risk acute lymphoblastic leukemia (ALL) in infants and early childhood. The t(4;11) translocation is one of the most frequent MLL translocations known today. In general, MLL translocations are the result of an illegitimate recombination process leading to reciprocal fusions of unrelated translocation partner (TP) genes with the MLL gene. Owing to the constant presence of the derivative (11) product, it was hypothesised that only MLL·TP fusion genes are responsible for the leukemogenic process. This concept has been successfully tested for some known MLL fusions, while other MLL fusions failed. Here, we demonstrate growth-transforming potential of AF4 wild-type and the AF4·MLL fusion protein. The underlying oncogenic mechanism involves the two E3 ubiquitin ligases SIAH1 and SIAH2, the N-terminal portion of AF4 and the protection of the AF4·MLL fusion protein against proteosomal degradation.

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Acknowledgements

We thank Drs T Nakamura and E Canaani for providing the affinity-purified polyclonal antiserum 173 directed against the MLL·C protein, Drs E Gillert and GH Fey for the 6E95 hybridoma cell line (monoclonal antibody anti-AF4·N; supported by DFG Grant FE 140/5-1 to GH Fey and Wilhelm-Sander Grant 96.047.1 to GH Fey and RM), and Dr U Bangerter and T Pranzl for the establishment of the MLL·AF4 and AF4·MLL cDNA cassettes. We also thank Drs M Karas and Ueli Schibler for critically reading the manuscript. This work has been funded by the DFG Grant Ma 1876/4-1 to RM.

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Authors and Affiliations

  1. Institute of Pharmaceutical Biology, Biocenter N230, University of Frankfurt/Main, Marie-Curie-Str. 9, Frankfurt/Main, D-60439, Germany

    Adelheid Bursen, Sven Moritz, Anne Gaussmann, Theo Dingermann & Rolf Marschalek

  2. Department of Cell Morphology and Molecular Neurobiology, Ruhr-University, Building NDEF 05/339, Universitätsstr. 150, Bochum, D-44801, Germany

    Sören Moritz

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  1. Adelheid Bursen
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Correspondence to Rolf Marschalek.

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Bursen, A., Moritz, S., Gaussmann, A. et al. Interaction of AF4 wild-type and AF4·MLL fusion protein with SIAH proteins: indication for t(4;11) pathobiology?. Oncogene 23, 6237–6249 (2004). https://doi.org/10.1038/sj.onc.1207837

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