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Protein Stops P53 In Its Tracks In Cancer Cells

Date:
February 21, 2007
Source:
Journal of Clinical Investigation
Summary:
Overexpression of a protein known as HMGA1 has been associated with many types of cancer in humans. Previous studies have shown that HMGA1 decreases the ability of p53 to inhibit cell death by a process known as apoptosis; inhibition of p53-mediated apoptosis causes tumors to develop in both animals and humans. However, precisely how HMGA1 mediates its pro-tumorigenic effects on p53 have not been clearly established.
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Overexpression of a protein known as HMGA1 has been associated with many types of cancer in humans. Previous studies have shown that HMGA1 decreases the ability of p53 to inhibit cell death by a process known as apoptosis; inhibition of p53-mediated apoptosis causes tumors to develop in both animals and humans.

However, precisely how HMGA1 mediates its pro-tumorigenic effects on p53 have not been clearly established.

Now, researchers from the Istituto Nazionale dei Tumori Regina Elena, Italy, show that in human cancer cell lines, HMGA1 inhibits p53-mediated apoptosis by interfering with the protein HIPK2, which helps p53 initiate apoptotic cell death.

In the study, which appears online on February 8 in advance of publication in the March print issue of the Journal of Clinical Investigation, Silvia Soddu and colleagues found that overexpression of HMGA1 inhibited p53-mediated apoptosis and caused HIPK2 to relocate from the cell nucleus to the cytoplasm. Further, expression of HIPK2 was required for HMGA1 to inhibit p53-mediated apoptosis.

Importantly, analysis of human breast cancer samples indicated that overexpression of HMGA1 correlated with the presence of HIPK2 in the cytoplasm and low levels of apoptotic cells, even in the presence of normal p53. This study therefore identifies a new mechanism by which p53-mediated apoptosis can be inhibited, leading to the development of cancer.


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The above post is reprinted from materials provided by Journal of Clinical Investigation. Note: Materials may be edited for content and length.


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Journal of Clinical Investigation. "Protein Stops P53 In Its Tracks In Cancer Cells." ScienceDaily. ScienceDaily, 21 February 2007. <www.sciencedaily.com/releases/2007/02/070208230747.htm>.
Journal of Clinical Investigation. (2007, February 21). Protein Stops P53 In Its Tracks In Cancer Cells. ScienceDaily. Retrieved July 1, 2015 from www.sciencedaily.com/releases/2007/02/070208230747.htm
Journal of Clinical Investigation. "Protein Stops P53 In Its Tracks In Cancer Cells." ScienceDaily. www.sciencedaily.com/releases/2007/02/070208230747.htm (accessed July 1, 2015).

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