Angiogenesis is a crucial physiological phenomenon in female reproductive cycle. A large body of experimental results indicates that physiological angiogenesis is under the control of sex hormones. The finding from our previous experimental results had shown that progesterone at physiologic levels increased the protein expression of p53 tumor suppressor gene, which in turn increased the levels of cyclin-dependent kinase inhibitor p21 and p27 protein, and finally led to the inhibition of cell proliferation. In the past, studies regarding p21 regulation had clearly illustrated that the p53 protein directly activated p21 expression though binding to the promoter of p21 gene. However, the p53-regulated p27 gene expression has not been reported before. The finding from our preceding experimental results had indicated that p53 induction could up-regulate p27 promoter activity, which in turn increased the mRNA and protein levels of p27. Moreover, we had found that p53 protein could associate with the p27 DNA. Therefore, the main goal of this proposed research study is to investigate further the molecular mechanism underlying p53 on regulation of p27 gene expression. Accordingly, the research proposal will further focus on examination of the regulatory and molecular mechanisms underlying control of p27 transcription and post-transcription. In the first part of this study, the research will be going to identify the precise binding domains of p53 protein on the p27 promoter and explore whether the p53 up-regulated p27 transcriptional activity is mediated by a direct p53 protein-p27 DNA binding or functionally active p53 protein tetramers. In the second part of this research, the role of p27 5’-UTR and p27 3’-UTR in the regulation of p27 post-transcription and the molecular mechanisms underlying p27 5’-UTR and p27 3’-UTR mediated regulation of p27 post-transcription will be investigated.
|Effective start/end date||8/1/13 → 7/31/14|
- p53 tumor suppressor gene
- p27 gene
- Cyclin-dependent kinase inhibitor
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