Human mitochondrial transcription factor A functions in both nuclei and mitochondria and regulates cancer cell growth
- 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 Environmental Health, Kitakyushu (Japan)
- Department of Urology, Shengjing Hospital of China Medical University, Shenyang (China)
- Department of Pathology, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima (Japan)
- Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu (Japan)
Highlights: {yields} Mitochondrial transcription factor A (mtTFA) localizes in nuclei and binds tightly to the nuclear chromatin. {yields} mtTFA contains two putative nuclear localization signals (NLS) in the HMG-boxes. {yields} Overexpression of mtTFA enhances the growth of cancer cells, whereas downregulation of mtTFA inhibits their growth by regulating mtTFA target genes, such as baculoviral IAP repeat-containing 5 (BIRC5; also known as survivin). {yields} Knockdown of mtTFA expression induces p21-dependent G1 cell cycle arrest. -- 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.
- OSTI ID:
- 22204894
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 408, Issue 1; Other Information: Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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