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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Chen RH, Chang TY . (1997). Involvement of caspase family proteases in transforming growth factor-beta-induced apoptosis. Cell Growth Differ 8: 821–827.
Costantini P, Jacotot E, Decaudin D, Kroemer G . (2000). Mitochondrion as a novel target of anticancer chemotherapy. J Natl Cancer Inst 92: 1042–1053.
Dang CV, Semenza GL . (1999). Oncogenic alterations of metabolism. Trends Biochem Sci 24: 68–72.
Debatin KM, Poncet D, Kroemer G . (2002). Chemotherapy: targeting the mitochondrial cell death pathway. Oncogene 21: 8786–8803.
Goldenthal MJ, Marin-Garcia J . (2004). Mitochondrial signaling pathways: a receiver/integrator organelle. Mol Cell Biochem 262: 1–16.
Hatakeyama S, Osawa M, Omine M, Ishikawa F . (1999). JTB: a novel membrane protein gene at 1q21 rearranged in a jumping translocation. Oncogene 18: 2085–2090.
Jang CW, Chen CH, Chen CC, Chen JY, Su YH, Chen RH . (2002). TGF-beta induces apoptosis through Smad-mediated expression of DAP-kinase. Nat Cell Biol 4: 51–58.
Kaelin Jr WG . (2005). ROS: really involved in oxygen sensing. Cell Metab 1: 357–358.
Keung YK, Yung C, Wong JW, Shah F, Cobos E, Tonk V . (1998). Unusual presentation of multiple myeloma with ‘jumping translocation’ involving 1q21. A case report and review of the literature. Cancer Genet Cytogenet 106: 135–139.
Kim SG, Jong HS, Kim TY, Lee JW, Kim NK, Hong SH et al. (2004). Transforming growth factor-beta 1 induces apoptosis through Fas ligand-independent activation of the Fas death pathway in human gastric SNU-620 carcinoma cells. Mol Biol Cell 15: 420–434.
Kim-Kaneyama JR, Suzuki W, Ichikawa K, Ohki T, Kohno Y, Sata M et al. (2005). Uni-axial stretching regulates intracellular localization of Hic-5 expressed in smooth-muscle cells in vivo. J Cell Sci 118: 937–949.
Kitamura T, Koshino Y, Shibata F, Oki T, Nakajima H, Nosaka T et al. (2003). Retrovirus-mediated gene transfer and expression cloning: powerful tools in functional genomics. Exp Hematol 31: 1007–1014.
Kondoh H, Lleonart ME, Gil J, Wang J, Degan P, Peters G et al. (2005). Glycolytic enzymes can modulate cellular life span. Cancer Res 65: 177–185.
Kroemer G . (2003). The mitochondrial permeability transition pore complex as a pharmacological target. An introduction. Curr Med Chem 10: 1469–1472.
Larisch S, Yi Y, Lotan R, Kerner H, Eimerl S, Tony Parks W et al. (2000). A novel mitochondrial septin-like protein, ARTS, mediates apoptosis dependent on its P-loop motif. Nat Cell Biol 2: 915–921.
Marchetti P, Mortier L, Beauvillain V, Formstecher P . (2002). Are mitochondria targets of anticancer drugs responsible for apoptosis? Ann Biol Clin (Paris) 60: 391–403.
Matoba S, Kang JG, Patino WD, Wragg A, Boehm M, Gavrilova O et al. (2006). p53 regulates mitochondrial respiration. Science 312: 1650–1653.
McKenzie M, Liolitsa D, Hanna MG . (2004). Mitochondrial disease: mutations and mechanisms. Neurochem Res 29: 589–600.
Mori K, Shibanuma M, Nose K . (2004). Invasive potential induced under long-term oxidative stress in mammary epithelial cells. Cancer Res 64: 7464–7472.
Pelicano H, Xu RH, Du M, Feng L, Sasaki R, Carew JS et al. (2006). Mitochondrial respiration defects in cancer cells cause activation of Akt survival pathway through a redox-mediated mechanism. J Cell Biol 175: 913–923.
Perlman R, Schiemann WP, Brooks MW, Lodish HF, Weinberg RA . (2001). TGF-beta-induced apoptosis is mediated by the adapter protein Daxx that facilitates JNK activation. Nat Cell Biol 3: 708–714.
Petros JA, Baumann AK, Ruiz-Pesini E, Amin MB, Sun CQ, Hall J et al. (2005). mtDNA mutations increase tumorigenicity in prostate cancer. Proc Natl Acad Sci USA 102: 719–724.
Rotem R, Heyfets A, Fingrut O, Blickstein D, Shaklai M, Flescher E . (2005). Jasmonates: novel anticancer agents acting directly and selectively on human cancer cell mitochondria. Cancer Res 65: 1984–1993.
Saltzman A, Munro R, Searfoss G, Franks C, Jaye M, Ivashchenko Y . (1998). Transforming growth factor-beta-mediated apoptosis in the Ramos B-lymphoma cell line is accompanied by caspase activation and Bcl-XL downregulation. Exp Cell Res 242: 244–254.
Shibanuma M, Kim-Kaneyama JR, Ishino K, Sakamoto N, Hishiki T, Yamaguchi K et al. (2003). Hic-5 communicates between focal adhesions and the nucleus through oxidant-sensitive nuclear export signal. Mol Biol Cell 14: 1158–1171.
Staniek K, Gille L, Kozlov AV, Nohl H . (2002). Mitochondrial superoxide radical formation is controlled by electron bifurcation to the high and low potential pathways. Free Radic Res 36: 381–387.
Warburg O . (1956). On respiratory impairment in cancer cells. Science 124: 269–270.
Wong N, Chan A, Lee SW, Lam E, To KF, Lai PB et al. (2003). Positional mapping for amplified DNA sequences on 1q21–q22 in hepatocellular carcinoma indicates candidate genes over-expression. J Hepatol 38: 298–306.
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.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
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
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1210423
Keywords
This article is cited by
-
Overexpression of DCF1 inhibits glioma through destruction of mitochondria and activation of apoptosis pathway
Scientific Reports (2014)
-
Chromosome 1q21 amplification and oncogenes in hepatocellular carcinoma
Acta Pharmacologica Sinica (2010)
-
Transcriptional induction of MMP-10 by TGF-β, mediated by activation of MEF2A and downregulation of class IIa HDACs
Oncogene (2010)
-
Jumping translocation in acute monocytic leukemia (M5b) with alternative breakpoint sites in the long arm of donor chromosome 3
Medical Oncology (2010)