Characterization of Jumping translocation breakpoint (JTB) gene product isolated as a TGF-beta1-inducible clone involved in regulation of mitochondrial function, cell growth and cell death.
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-beta1-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-beta1-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.
Kanome
T
T
Department of Microbiology, Showa University School of Pharmaceutical Sciences, Tokyo, Japan.
Itoh
N
N
Ishikawa
F
F
Mori
K
K
Kim-Kaneyama
J-R
JR
Nose
K
K
Shibanuma
M
M
D000818:Animals; D017209:Apoptosis; D016923:Cell Death / Q000502:physiology*; D002455:Cell Division / Q000502:physiology*; D019457:Chromosome Breakage; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D004847:Epithelial Cells / Q000502:physiology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020071:Interspersed Repetitive Sequences; D008321:Mammary Glands, Animal / Q000166:cytology; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008928:Mitochondria / Q000235:genetics / Q000502:physiology*; D009369:Neoplasms / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012016:Reference Values; D014178:Translocation, Genetic
D012333:RNA, Messenger