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在电离辐射的癌细胞中，HuR 通过 ATM/p38 依赖性方式稳定 TFAM mRNA。

HuR stabilizes TFAM mRNA in an ATM/p38-dependent manner in ionizing irradiated cancer cells.

机构信息

Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Chinese Academy of Sciences, Hefei, China.

University of Science and Technology of China, Hefei, China.

出版信息

Cancer Sci. 2018 Aug;109(8):2446-2457. doi: 10.1111/cas.13657. Epub 2018 Jun 28.

DOI:10.1111/cas.13657
PMID:29856906
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6113444/
Abstract

Mitochondrial transcription factor A (TFAM) plays key roles in transcription and maintenance of mtDNA. It has been reported that TFAM could promote the proliferation and tumorigenesis of cells under stressed conditions. Previous evidence showed ionizing radiation stimulated the expression of TFAM, the replication of mtDNA, and the activity of mtDNA-encoded cytochrome C oxidase. However, little is known about the mechanism of TFAM regulation in irradiated cells. In this article, we explored the role of mRNA stability in regulating TFAM expression in irradiated cancer cells. Our results showed that radiation stimulated the levels of TFAM mRNA and protein. RNA-binding protein HuR associated and stabilized TFAM mRNA to facilitate the expression of TFAM, which was enhanced by radiation. Furthermore, radiation-activated ataxia-telangiectasia mutated kinase/p38 signaling positively contributed to the nucleus to cytosol translocation of HuR, its binding and stabilization of TFAM mRNA, without affecting the transcription and the stability of TFAM. Our current work proposed a new mechanism of DNA damage response-regulated mitochondrial function variations, and indicated that TFAM might be a potential target for increasing the sensitization of cancer cells to radiotherapy.

摘要

线粒体转录因子 A（TFAM）在转录和维持 mtDNA 中发挥关键作用。有报道称，TFAM 可在应激条件下促进细胞的增殖和肿瘤发生。先前的证据表明，电离辐射刺激 TFAM 的表达、mtDNA 的复制和 mtDNA 编码的细胞色素 C 氧化酶的活性。然而，关于辐射细胞中 TFAM 调节的机制知之甚少。在本文中，我们探讨了 mRNA 稳定性在调节辐射癌细胞中 TFAM 表达中的作用。我们的结果表明，辐射刺激了 TFAM mRNA 和蛋白的水平。RNA 结合蛋白 HuR 与 TFAM mRNA 结合并稳定它，从而促进 TFAM 的表达，而辐射则增强了这一过程。此外，辐射激活的共济失调毛细血管扩张突变激酶/p38 信号正向促进 HuR 从核到细胞质的易位、其与 TFAM mRNA 的结合和稳定，而不影响 TFAM 的转录和稳定性。我们目前的工作提出了一种新的 DNA 损伤反应调节线粒体功能变化的机制，并表明 TFAM 可能是增加癌细胞对放疗敏感性的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88ec/6113444/8653583f144b/CAS-109-2446-g011.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88ec/6113444/8653583f144b/CAS-109-2446-g011.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88ec/6113444/b72cb86e572f/CAS-109-2446-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88ec/6113444/f68f214c56af/CAS-109-2446-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88ec/6113444/71c94c59876a/CAS-109-2446-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88ec/6113444/b9cc16190a65/CAS-109-2446-g009.jpg
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6
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