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- Title
TCP80 and RHA are positive p53 IRES trans-acting factors poorly expressed in cancer cells with defective response to DNA damage.
- Authors
Halaby, Marie-jo; Jiang, Hong; Miskimins, W. Keith; Yang, Da-Qing
- Abstract
The tumor suppressor p53 is essential for the protection of cells against tumorigenic transformation. The p53 protein accumulates in the cell following stressful events such as DNA damage. Induction of the p53 protein following genotoxic stress is known to be regulated at the level of translation. An internal ribosome entry site (IRES) located at the 5'-untranslated region of the p53 mRNA was recently identified. Using small interfering RNA and plasmid DNA transfection experiments, we have identified two p53 IRES-trans acting factors (ITAFs), TCP80 (translational control protein 80) and RHA (RNA helicase A), that positively regulate p53 IRES activity following DNA damage. Furthermore, we demonstrate that two breast cancer cell lines known to harbor wild-type p53 have defective p53 induction and diminished p53 IRES activity in response to DNA damage. Moreover, the expression levels of TCP80 and RHA are low in these cells, and overexpression of either protein has no effect on p53 IRES activity. A significant increase in p53 IRES activity was observed only when TCP80 and RHA were co-expressed in these two cell lines. Our results suggest that the positive ITAFs of the p53 IRES are important for p53 induction following DNA damage and that defective expression of these ITAFs may be involved in the development of cancer. Funding for this research was provided by an Idea Award (grant #BC051719) from the Department of Defense.
- Publication
FASEB Journal, 2008, Vol 22, p217
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fasebj.22.2_supplement.217