Department of Molecular Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. ; Department of Urology, School of Medicine, University of Occupational and
Biochem Biophys Res Commun. 2011 Apr 29;408(1):45-51. doi: 10.1016/j.bbrc.2011.03.114. Epub 2011 Mar 29.
Mitochondrial transcription factor A (mtTFA) is one of the high mobility group protein family and is required for both transcription from and maintenance of mitochondrial genomes. However, the roles of mtTFA have not been extensively studied in cancer cells. Here, we firstly reported the nuclear localization of mtTFA. The proportion of nuclear-localized mtTFA varied among different cancer cells. Some mtTFA binds tightly to the nuclear chromatin. DNA microarray and chromatin immunoprecipitation assays showed that mtTFA can regulate the expression of nuclear genes. Overexpression of mtTFA enhanced the growth of cancer cell lines, whereas downregulation of mtTFA inhibited their growth by regulating mtTFA target genes, such as baculoviral IAP repeat-containing 5 (BIRC5; also known as survivin). Knockdown of mtTFA expression induced p21-dependent G1 cell cycle arrest. These results imply that mtTFA functions in both nuclei and mitochondria to promote cell growth.
线粒体转录因子 A（mtTFA）是高迁移率族蛋白家族的一员，对于线粒体基因组的转录和维持都是必需的。然而，mtTFA 在癌细胞中的作用尚未得到广泛研究。在这里，我们首次报道了 mtTFA 的核定位。不同癌细胞中线粒体转录因子 A 的核定位比例不同。一些 mtTFA 与核染色质紧密结合。DNA 微阵列和染色质免疫沉淀分析表明，mtTFA 可以调节核基因的表达。mtTFA 的过表达增强了癌细胞系的生长，而 mtTFA 的下调通过调节 mtTFA 靶基因（如杆状病毒 IAP 重复包含 5（BIRC5；也称为生存素））抑制其生长。mtTFA 表达的敲低诱导 p21 依赖性 G1 细胞周期阻滞。这些结果表明，mtTFA 在细胞核和线粒体中都发挥作用，以促进细胞生长。
