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Human DDA3 is an oncoprotein down-regulated by p53 and DNA damage
Wang-Ju Hsieh1, Shu-Chen Hsieh, Chia-Chen Chen
1Institute of Biochemistry and Molecular Biology, National Yang-Ming University, 155 Li-Nong Street, Section 2, Taipei 112, Taiwan.
Biochemical and Biophysical Research Communications
|February 23, 2008
Summary
Human DDA3 (hDDA3) is suppressed by p53 and DNA damage, unlike its mouse counterpart. This p53-regulated gene exhibits oncogenic characteristics, promoting cell growth and appearing in liver cancer tissues.
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- Mouse DDA3 (mDDA3), a microtubule-associated protein, promotes cell growth and is activated by DNA damage via p53.
- Human DDA3 (hDDA3) differs from mDDA3, lacking a key p53 binding motif found in mice.
Purpose of the Study:
- To investigate the regulation of human DDA3 (hDDA3) by p53 and its role in DNA damage response.
- To determine the functional and oncogenic characteristics of hDDA3.
Main Methods:
- Chromatin immunoprecipitation (ChIP) to identify p53 binding sites on the hDDA3 gene.
- Luciferase reporter assays to assess p53-mediated transcriptional regulation of hDDA3.
- Analysis of hDDA3 mRNA and protein levels in response to DNA damage and p53 expression.
Main Results:
- p53 suppresses hDDA3 mRNA and protein levels in cells with wild-type p53, particularly after DNA damage.
- Three p53 binding motifs (El-Deiry decamers) were identified in the hDDA3 promoter region.
- The hDDA3 promoter with the p53 binding motif mediated p53-induced repression.
- hDDA3 expression reduced serum dependency in cells and was overexpressed in hepatoma tissues.
Conclusions:
- hDDA3 is a novel p53- and DNA-damage-down-regulated target gene.
- hDDA3 possesses oncogenic properties, suggesting a role in cancer development.
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