title: Human mitochondrial transcription factor A functions in both nuclei and mitochondria and regulates cancer cell growth.
abstract: 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.
authors: 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
authors: Bin
authors: B
authors: Han
authors: Hiroto
authors: H
authors: Izumi
authors: Yoshihiro
authors: Y
authors: Yasuniwa
authors: Masaki
authors: M
authors: Akiyama
authors: Takahiro
authors: T
authors: Yamaguchi
authors: Naohiro
authors: N
authors: Fujimoto
authors: Tetsuro
authors: T
authors: Matsumoto
authors: Bin
authors: B
authors: Wu
authors: Akihide
authors: A
authors: Tanimoto
authors: Yasuyuki
authors: Y
authors: Sasaguri
authors: Kimitoshi
authors: K
authors: Kohno
mesh_terms: D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D016193:G1 Phase / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics; D008297:Male; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D000077022:Survivin; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C107489:BIRC5 protein, human; D004268:DNA-Binding Proteins; D051034:Inhibitor of Apoptosis Proteins; D024101:Mitochondrial Proteins; D000077022:Survivin; D014157:Transcription Factors; C422562:mitochondrial transcription factor A