The p53 tumour suppressor gene
eliminates tumour cells by activating cell cycle
arrest and cell death pathways. However, in the
majority of human tumours p53 is inactivated by
minor genetic mutations that disable these functions
and allow tumourigenic cells to proliferate. It
is apparent though that non-functional p53 often
accumulates to high levels in tumour cells and
we are attempting to find ways to re-activate
these proteins.
Using a small molecule inhibitor of the interaction
between p53 and its major regulator MDM-2 we have
been able to mimic the accumulation of p53 in
cells in the absence of oncogenic stimuli. Interestingly,
this accumulation only activates cell cycle arrest
pathways and does not result in significant cell
death. Thus, it appears that oncogenic stimuli
initiate interactions with the p53 protein that
are responsible for activating p53's apoptotic
capabilities. We are attempting to identify interactions
that increase the apoptotic response of p53 and
to use these to design new drugs that could potentially
be used to re-activate p53's apoptotic capabilities
in tumour cells.
Contact Details of Program Leader
Name: Dr Brett Dix
Institution: WABRI - Curtin University
Ph: +61 8 9362 4963
Fax: +61 8 9361 2027
Email:
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