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Characterization of Jumping translocation breakpoint (JTB) gene product isolated as a TGF-β1-inducible clone involved in regulation of mitochondrial function, cell growth and cell death

Oncogene volume 26, pages 5991–6001 (2007)Cite this article

Abstract

Jumping translocation breakpoint (JTB) is a gene located on human chromosome 1 at q21 that suffers an unbalanced translocation in various types of cancers, and potentially encodes a transmembrane protein of unknown function. The results of cancer profiling indicated that its expression was suppressed in many cancers from different organs, implying a role in the neoplastic transformation of cells. Recently, we isolated JTB as a TGF-β1-inducible clone by differential screening. In this study, we characterized its product and biological functions. We found that it was processed at the N-terminus and located mostly in mitochondria. When expressed in cells, JTB-induced clustering of mitochondria around the nuclear periphery and swelling of each mitochondrion. In those mitochondria, membrane potential, as monitored with a JC-1 probe, was significantly reduced. Coinciding with these changes in mitochondria, JTB retarded the growth of the cells and conferred resistance to TGF-β1-induced apoptosis. These activities were dependent on the N-terminal processing and induced by wild-type JTB but not by a mutant resistant to cleavage. These findings raised the possibility that aberration of JTB in structure or expression induced neoplastic changes in cells through dysfunction of mitochondria leading to deregulated cell growth and/or death.

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Acknowledgements

This work was supported in part by Grants-in-Aid for Scientific Research and the High-Technology Research Center Project from the Ministry for Education, Science, Sports and Culture of Japan. We thank Dr Kitamura (University of Tokyo) for generously donating the pMX retroviral vector. We also thank A Sakurai and A Takahashi for contributing to this work as the theme for their bachelors’ degrees.

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  1. Department of Microbiology, Showa University School of Pharmaceutical Sciences, Tokyo, Japan

    T Kanome, N Itoh, F Ishikawa, K Mori, J-R Kim-Kaneyama, K Nose & M Shibanuma

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  1. T Kanome
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  2. N Itoh
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  3. F Ishikawa
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  4. K Mori
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  6. K Nose
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Correspondence to M Shibanuma.

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Kanome, T., Itoh, N., Ishikawa, F. et al. Characterization of Jumping translocation breakpoint (JTB) gene product isolated as a TGF-β1-inducible clone involved in regulation of mitochondrial function, cell growth and cell death. Oncogene 26, 5991–6001 (2007). https://doi.org/10.1038/sj.onc.1210423

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