Mitochondrial transcription factor A and its downstream targets are up-regulated in a rat hepatoma (Retracted article. See vol. 293, pg. 12947, 2018)
Mitochondrial transcription factor A and its downstream targets are up-regulated in a rat hepatoma (Retracted article. See vol. 293, pg. 12947, 2018)
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DOI：
10.1074/jbc.m206958200
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发表时间：
2002-11-08
影响因子：
4.8
通讯作者：
Jacob, ST
中科院分区：
文献类型：
--
作者：
Dong, XC;Ghoshal, K;Jacob, ST
线粒体转录因子A是线粒体DNA转录和复制的关键调控因子。在低分化的大鼠肝癌Morris肝癌3924A中，该因子的mRNA和蛋白水平分别比宿主肝脏高出约10倍和11倍。TFAM下游靶基因肝癌细胞色素c氧化酶1、11和NADH脱氢酶5，6的mRNA水平分别增加10倍、8倍、5倍和3倍。有趣的是，在肝癌细胞核中也发现了TFAM。核呼吸因子1和2(NRF-1和NRF-2)是已知与人TFAM启动子上的特定调控元件相互作用的蛋白质，其在肝癌中的mRNA水平分别是宿主肝的5倍和3倍。与人类启动子不同，大鼠Tfam启动子不与肝或肝癌核提取液中的NRF-1形成特异性复合体，这与大鼠近端启动子中缺乏NRF-1共同序列一致。在两种提取物中，大鼠启动子和NRF-2蛋白之间形成的单一特异性复合体具有可比性。肝癌核提取液中Sp1的DNA结合活性是肝提取液中的4倍。体内基因组足迹显示NRF-2和Sp1共同位于大鼠Tfam基因启动子上。TFAM也被上调了监管。在其他肝癌细胞中。综上所述，这些结果表明Tfam在一些肿瘤中上调，特别是在肝脏肿瘤中。此外，肝癌中相对较高水平的Sp1与启动子的结合可能在这些肿瘤细胞中Tfam的上调中起主要作用。
Mitochondrial transcription factor A is a key regulator involved in mitochondrial DNA transcription and replication. In a poorly differentiated rat hepatoma, Morris hepatoma 3924A, the mRNA and protein levels of this factor were elevated about 10- and 11-fold, respectively, relative to the host liver. The mRNA levels for the hepatoma cytochrome c oxidase 1, 11, and NADH dehydrogenase 5,6, the downstream targets of Tfam, were augmented 10-, 8-, 5-, and 3-fold, respectively. Interestingly, Tfam was also found in the hepatoma nucleus. The mRNA levels for nuclear respiratory factor 1 and 2 (NRF-1 and -2), the proteins that are known to interact with specific regulatory elements on human TFAM promoter, were 5- and 3-fold higher, respectively, in the hepatoma relative to the host liver. Unlike the human promoter, the rat Tfam promoter did not form a specific complex with the NRF-1 in the liver or hepatoma nuclear extracts, which is consistent with the absence of an NRF-1 consensus sequence in the proximal rat promoter. A single specific complex formed between the rat promoter and the NRF-2 protein was comparable in the two extracts. The DNA binding activity of Sp1 in the hepatoma nuclear extract was 4-fold greater than that in the liver extract. In vivo genomic footprinting showed occupancy of NRF-2 and Sp1 consensus sites on the promoter of rat Tfam gene. Tfam was also up-regulated. in other hepatoma cells. Together, these results show up-regulation of Tfam in some tumors, particularly the liver tumors. Further, the relatively high level of Sp1 binding to the promoter in the hepatoma could play a major role in the up-regulation of Tfam in these tumor cells.