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Human mitochondrial transcription factor A functions in both nuclei and mitochondria and regulates cancer cell growth

Han, Bin, Izumi, Hiroto, Yasuniwa, Yoshihiro, Akiyama, Masaki, Yamaguchi, Takahiro, Fujimoto, Naohiro, Matsumoto, Tetsuro, Wu, Bin, Tanimoto, Akihide, Sasaguri, Yasuyuki, Kohno, Kimitoshi
Biochemical and biophysical research communications 2011 v.408 no.1 pp. 45-51
DNA microarrays, cell cycle, cell growth, chromatin, gene expression regulation, gene overexpression, genes, growth retardation, humans, mitochondria, mitochondrial genome, neoplasm cells, precipitin tests, transcription (genetics), transcription factors
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.