Ying Chan: Module 3 Project

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Module 3 Project

Topic in Consideration: Which genes are affected by p53 and are they related? What to do with p53?

Ideas: Make cDNA from WT mice with p53 and p53-null mice and look at differential gene expession using microarray. Find relationship between genes downregulated/upregulated in null mice.

1)“Wild-type p53 and p73 negatively regulate expression of proliferation related genes.”

p53 and its homologue, p73, cause cell arrest and death. A couple of genes were identified that were regulated by p53; a promoter with an E21 site was necessary for repression. Cancer cells with WT p53 showed repression of cyclin B2(involved in cell cycle), suggesting that DNA damage triggers repression of genes involved in cell growth.

2) "Molecular approaches to cervical cancer therapy.”
In human papilloma virus strains HPV-16 and HPV-18, the viral oncogenes E6 and E7 inhibit p53 and p107(Rb) and modify the cell cycle. Treatment of HPV with TNAs(therapeutic nucleic acids), such as siRNAs and anti-sense oligonucleotides may block the onset of cervical cancer.

3) “microRNAs join the p53 network--another piece in the tumour-suppression puzzle.”
miR-34 activation is required for p53-mediated cell death; miR-34 is a p53 transcriptional target. A question to explore would be what other miRNAs are affected by p53 and what genes are targeted by those miRNAs.