Abstract
A40
p53 has been known to play an important role as an tumor suppressor gene for the maintaining of genome stability. In the field of cancer prevention study, p53 has been issued to clarify the mechanism of activation under the non-genotoxic cancer preventive agents containing antioxidant selenium. In previous our study, p53 has been reported to be the function of transcriptional activation activated without the genotoxicity through the redox modulation in response to selenomethionine (SeMet). In this study, we investigated that the mechanism of p53 protein stabilization enhanced by SeMet. Our data showed that the ubiquitinated p53 was decreased in the cells exhibiting the downregulation of JNK which is one of E3-ubiquitin ligases compared with in mock-treated cells suggesting that the JNK-modulated p53 ubiquitination might be inhibited by SeMet. To define the mechanism of the enhanced p53 stability in the presence of SeMet, redox factor 1 (Ref-1) which has been documented as one of the factors modulating the redox status in response to antioxidants was downregulated using siRNA. Our data showed the first time that the interaction of JNK and p53 was increased in Ref-1 siRNA-treated cells in the presence of SeMet implicating that the Ref-1 activated by SeMet might be involved in the inhibition of JNK-mediated p53 ubiquitination. Our study suggested that the enhancement of p53 stabilization in response to SeMet might provide an important clue for the cancer prevention.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A40.
Seventh AACR International Conference on Frontiers in Cancer Prevention Research-- Nov 16-19, 2008; Washington, DC
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