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
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
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DOI：
10.1038/sj.onc.1210423
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发表时间：
2007-09-01
期刊：
影响因子：
8
通讯作者：
Shibanuma, M.
中科院分区：
文献类型：
--
作者：
Kanome, T.;Itoh, N.;Shibanuma, M.
跳跃易位断点 (JTB) 是位于人类 1 号染色体 q21 上的一个基因，在各种类型的癌症中遭受不平衡易位，并可能编码功能未知的跨膜蛋白。癌症亲的结果。 ling指出，它的表达在来自不同器官的许多癌症中受到抑制，这意味着它在细胞的肿瘤转化中发挥作用。最近，我们通过差异筛选分离出 JTB 作为 TGF-β1 诱导克隆。在这项研究中，我们表征了其产物和生物学功能。我们发现它是在 N 末端加工的，并且主要位于线粒体中。当在细胞中表达时，JTB-诱导线粒体在核周边聚集以及每个线粒体肿胀。在这些线粒体中，用 JC-1 探针监测的膜电位显着降低。与线粒体的这些变化相一致，JTB 延缓了细胞的生长，并赋予了对 TGF-β1 诱导的细胞凋亡的抵抗力。这些活性依赖于N-末端加工并由野生型JTB诱导，但不是由抗切割突变体诱导。这些发现提出了一种可能性，即 JTB 结构或表达的畸变通过线粒体功能障碍导致细胞生长失调和/或死亡，从而诱导细胞发生肿瘤性变化。
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 pro. ling 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-beta 1-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-beta 1-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.