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A human homolog of Drosophila lethal(3)malignant brain tumor (l(3)mbt) protein associates with condensed mitotic chromosomes

Oncogene volume 18, pages 3799–3809 (1999)Cite this article

Abstract

The lethal(3)malignant brain tumor (D-l(3)mbt) gene is considered to be one of the tumor suppressor genes of Drosophila, and its recessive mutations are associated with malignant transformation of the neuroblasts in the larval brain. The structure of D-l(3)mbt protein is similar to Drosophila sex comb on midleg (Scm) protein which is a member of Polycomb group (PcG) proteins. We have isolated here the first human homolog of the D-l(3)mbt gene, designated h-l(3)mbt. Radiation hybrid mapping and fluorescence in situ hybridization (FISH) analysis localized the h-l(3)mbt gene to chromosome 20q12. The h-l(3)mbt transcript is expressed in most of the human adult normal tissues and cultured cell lines. However, some cancer cells markedly reduce the h-l(3)mbt protein expression. Immunocytochemical study revealed that the h-l(3)mbt protein shows a speckled and scattered distribution in interphase nuclei and completely associates with condensed chromosomes in mitotic cells. This subcellular localization has been shown to be different from that of Bmi1 protein which is a component of PcG complex. Furthermore, overexpression of h-l(3)mbt protein by using a Cre-mediated gene activation system leads to failures of proper chromosome segregation and cytokinesis, which result in formation of multinuclei in U251MG cells. These observations suggest that h-l(3)mbt protein has functions distinct from those of PcG proteins and may play a role in proper progression of cell division.

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Acknowledgements

We thank Drs A Kikuchi (Department of Biochemi., Hiroshima University), and H Maruta (Ludwig Institute for Cancer Research) for providing the pBJ-Myc and the pGEX-2TH plasmids, respectively; Dr M von Lohuizen (Department of Molecular Carcinogenesis, The Netherlands Cancer Institute) for providing F6 anti-Bmi1 monoclonal antibody; Drs I Saitoh and Y Kanegae (Laboratory of Molecular Genetics, Institute of Medical Science, the University of Tokyo) for providing the Cre-loxP gene activation system; Dr T Kishimoto (Biomedical R&D Department, Sumitomo Electric Industries) for assistance in antibody production: Dr K Akagi (Saitama Cancer Center) for valuable discussion; and T Arino for secretarial assistance. This work was supported by a grant for Cancer Research from the Ministry of Education, Science and Culture of Japan (Hideyuki Saya).

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  1. Department of Tumor Genetics and Biology, Kumamoto University School of Medicine, 2-2-1 Honjo Kumamoto, 860-0811, Japan

    Hisashi Koga, Shin-ichi Matsui, Toru Hirota & Hideyuki Saya

  2. Laboratory of Biological Chemistry, Faculty of Bioresources, Mie University, 1515 Kamihama, Tsu, 514-8507, Mie, Japan

    Shin-ichiro Takebayashi & Katsuzumi Okumura

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  1. Hisashi Koga
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Koga, H., Matsui, Si., Hirota, T. et al. A human homolog of Drosophila lethal(3)malignant brain tumor (l(3)mbt) protein associates with condensed mitotic chromosomes. Oncogene 18, 3799–3809 (1999). https://doi.org/10.1038/sj.onc.1202732

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