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A novel regulator of the p53-mediated mitochondrial apoptotic pathway
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- Faculty of Medicine, Biochemisty & Molecular Biology
- University of Calgary, Biochemistry and Molecular Biology
- Clark H. Smith Brain Tumor Center,
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- Document Type:
- Manuscript
- Date:
- Received 15 May 2008 07:13 UTC; Posted 16 May 2008
- Subjects:
- Cancer, Molecular Cell Biology
- Abstract:
The p53 tumor suppressor protein induces apoptosis in response to genotoxic and environmental stress. Recent studies have revealed the existence of a transcription-independent mitochondrial p53 apoptosis pathway, however the mechanism regulating p53 translocation to mitochondria and subsequent initiation of apoptosis was not known. Here, we show that Tid1, also known as mtHsp40 or Dnaja3, interacts with p53 and directs its translocation to mitochondria in cells exposed to hypoxia. Overexpression of Tid1 in tumor cells promoted mitochondrial localization of both wildtype and mutant forms of p53 and was able to restore the pro-apoptotic activity of mutant p53 proteins that were otherwise unable to induce apoptosis. Tid1's mitochondrial signal sequence and DnaJ domain were both required for the movement of the p53-Tid1 complex from the cytosol to the mitochondria. Our findings establish Tid1 as a novel regulator of p53 localization and apoptotic function.
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- This document is licensed to the public under the Creative Commons Attribution 3.0 License
- How to cite this document:
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Ahn, Bo Young, Trinh, Diane, Zajchowski, Laura, and Kim, Sung-Woo. A novel regulator of the p53-mediated mitochondrial apoptotic pathway. Available from Nature Precedings <http://hdl.handle.net/10101/npre.2008.1892.1> (2008)
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