1. Role of the p53 isoforms in cancer

We are using mouse models and in vitro studies to investigate the role of the p53 isoform D133p53 in the context of tumourigenesis and cancer progression. This naturally occurring isoform of p53 appears to act against normal p53 and has elevated expression in some malignancies. Interestingly, our laboratory recently generated a mouse model for expression of this isoform and found that the animals suffer from widespread inflammatory disease. This work is being undertaken by PhD candidate Imogen Roth, Assistant Research Fellows Michelle Wilson, Katie Young and Dr. Kunyu Li.

2. Interactions between Y-box binding protein YBX-1 and p53

YBX-1 is a multi-functional protein that can promote cancer formation and is highly expressed in advanced cancers.  Interestingly, YB-1 binds to p53.  YBX-1 is located in the cytoplasm of cells but upon stress treatment can translocate to the nucleus and function as a transcription factor, regulating gene expression.  We have shown that p53 helps YBX-1 shift to the nucleus where it can prevent p53 dependent apoptosis.  We have also shown that inhibition of YBX-1 leads to cell death that requires p53. We are continuing to study the interactions between YBX-1 and p53 to understand how they affect each other, with the goal of using YBX-1 as a new therapeutic target in the treatment of cancer. This work is being undertaken by Assistant Research Fellow Katie Young and Dr. Sunali Mehta.

3. p63 mediated control of IL-6

P53 also has two close homologue proteins called p63 and p73. P53 is known to negatively control IL-6, an important protein in cancer progression. This work is examining the influence that these related proteins have on IL-6 and its relevance to cancer progression. This work in being undertaken by Dr. Nicholas Fleming and co-workers.