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Molecular Cytogenetics

The interaction between EEN and Abi-1, two MLLfusion partners, and synaptojanin and dynamin: implications for leukaemogenesis

Leukemia volume 14, pages 594–601 (2000)Cite this article

Abstract

The mixed lineage leukaemia gene, MLL (also called HRX, ALL-1) in acute leukaemia is fused to at least 16 identified partner genes that display diverse structural and biochemical properties. Using GST pull down and the yeast two hybrid system, we show that two different MLL fusion partners with SH3 domains, EEN and Abi-1, interact with dynamin and synaptojanin, both of which are involved in endocytosis. Synaptojanin, a member of the inositol phosphatase family that has recently been shown to regulate cell proliferation and survival, is also known to bind to Eps15, the mouse homologue of AF1p, another fusion partner of MLL. Expression studies show that synaptojanin is strongly expressed in bone marrow and immature leukaemic cell lines, very weakly in peripheral blood leukocytes and absent in Raji, a mature B cell line. We found that the SH3 domains of EEN and Abi-1 interact with different proline-rich domains of synaptojanin while the EH domains of Eps15 interact with the NPF motifs of synaptojanin. In vitro competitive binding assays demonstrate that EEN displays stronger binding affinity than Abi-1 and may compete with it for synaptojanin. These findings suggest a potential link between MLLfusion-mediated leukaemogenesis and the inositol-signalling pathway.

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Acknowledgements

We thank Professor P De Camilli for dynamin and synaptojanin constructs, Professor SP Goff for mouse Abi-1 cDNA, Dr DY Jin for providing the control constructs of human Int-6 protein and HTLV-1 Tax and technical advice on yeast two hybrid studies, Stanley Ko for excellent technical support, Professor Mel Greaves and Dr Leanne Wiedemann for critical review of the manuscript. This work is supported by HKU RGC grant 338/046/0009.

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  1. Department of Pathology, The University of Hong Kong, Pokfulam, Hong Kong

    CW So, CKC So, N Cheung, SL Chew & LC Chan

  2. Department of Biochemistry, The University of Hong Kong, Pokfulam, Hong Kong

    MH Sham

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So, C., So, C., Cheung, N. et al. The interaction between EEN and Abi-1, two MLLfusion partners, and synaptojanin and dynamin: implications for leukaemogenesis. Leukemia 14, 594–601 (2000). https://doi.org/10.1038/sj.leu.2401692

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