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cDNA cloning and characterization of a novel gene encoding the MLF1-interacting protein MLF1IP

Oncogene volume 23, pages 3700–3707 (2004)Cite this article

Abstract

Myelodysplasia/acute myeloid leukemia (MDS/AML) is characterized by a t(3;5)(q25.1;q34) chromosomal translocation that forms a fusion gene between nucleophosmin (NPM) and MDS/myeloid leukemia factor 1 (MLF1). We identified a novel protein, MLF1-interacting protein (MLF1IP), that specifically associates with MLF1 by yeast two-hybrid analysis and in pulldown assays, and colocalizes with it in both the nuclei and cytoplasm of cells. The MLF1IP gene locus is at chromosome 4q35.1 and is composed of 14 exons spanning 75.8 kb of genomic DNA. The MLF1IP cDNA encodes a 46-kDa protein that contains two bipartite and two classical nuclear localization signals, two nuclear receptor-binding motifs (LXXLL), two leucine zippers, two PEST residues and several potential phosphorylation sites. MLF1IP transcripts are expressed in a variety of tissues (e.g. fetal liver, bone marrow, thymus and testis). MLF1IP appears to be a lineage-specific gene whose expression is confined exclusively to the CFU-E erythroid precursor cells, but not in mature erythrocytes. These observations, together with previous data demonstrating a role for MLF1 in suppressing red cell maturation, suggest a possible role for MLF1IP and MLF1 deregulation in the genesis of erythroleukemias.

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Acknowledgements

We thank Dr ST Kitai for helpful discussions and critical reading of the manuscript. This work was supported by a grant from University of Tennessee Health Science Center CNBD (Drs Kitai and Robertson, PIs) and Methodist Foundation (Dr Robertson, PI), and by grants to Dr SW Morris from the National Cancer Institute CA76301, Cancer Center Support (CORE) grant CA27165 and by the American Lebanese Syrian Associated Charities (ALSAC), St. Jude Children's Research Hospital.

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Authors and Affiliations

  1. Department of Neurosurgery, The University of Tennessee Health Science Center, 847 Monroe, Room 427, Memphis, 38163, TN, USA

    Silva H Hanissian, Umar Akbar, Bin Teng, Zorica Janjetovic & Jon H Robertson

  2. Center for Biochemistry and Molecular Biology, Christian-Albrechts University, Am Botanischen Garten 1-9, Kiel, 24118, Germany

    Anne Hoffmann

  3. Department of Pediatrics, Division of Hematology/Oncology, Cancer and Blood, The Hospital for Sick Children, University of Toronto, Ontario, Canada

    Johann K Hitzler

  4. The Ontario Cancer Institute and the Department of Medical Biophysics, University of Toronto, Ontario, Canada

    Norman Iscove

  5. Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center, Memphis, 38163, TN, USA

    Kristin Hamre, Xiaoping Du & Yiai Tong

  6. Hartwell Center for Bioinformatics and Biotechnology, St Jude Children's Research Hospital, Memphis, TN, USA

    Suraj Mukatira

  7. Department of Pediatrics, The University of Tennessee Health Science Center, Memphis, 38163, TN, USA

    Stephan W Morris

  8. Department of Pathology, St Jude Children's Research Hospital, Memphis, TN, USA

    Stephan W Morris

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  1. Silva H Hanissian
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  2. Umar Akbar
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  3. Bin Teng
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  8. Kristin Hamre
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  9. Xiaoping Du
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  11. Suraj Mukatira
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  12. Jon H Robertson
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  13. Stephan W Morris
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Correspondence to Silva H Hanissian.

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Hanissian, S., Akbar, U., Teng, B. et al. cDNA cloning and characterization of a novel gene encoding the MLF1-interacting protein MLF1IP. Oncogene 23, 3700–3707 (2004). https://doi.org/10.1038/sj.onc.1207448

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