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Review
p63: The Phantom of the Tumor Suppressor
Lee E. Finlan and Ted R. Hupp
volume 6 | issue 9
2 May 2007Pages: 1062 - 1071
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The last 20 years of research into p53 function has revealed some fascinating discoveries into the orchestration of tumour suppressor pathways with a multitude of putative drug targets being investigated. However, it was not until 1998 that the ancestral mother of p53 was documented. The eldest evolutionary conserved homologue of the p53 family is known today as p63. Originally, it was thought p63 was another tumour suppressor that could function in a similar capacity to p53. However, elegant demonstrations of the divergent roles that p63 plays as a key transcriptional regulator of the proliferation and differentiation cascade in stratified epithelia are documented. These data link ΔΝp63α to adult tissue stem cell regulation and possibly “cancer stem cells”. p63 lacks mutation in cancer development, which is in stark contrast to the classically high mutation status of p53 in a large compendium of cancer types. Perhaps suggesting a selective preference for p53 mutation. Why is p63 rarely mutated despite being part of the same gene family? Interestingly, p63 is often over-expressed and amplified in cancer, thus revealing a paradox. Is p63 required to provide cancer cell populations with a selective advantage as much as a loss of p53 function by mutation? Has p53 been masking a “phantom” with promising features as a target for drug development? Can we exploit the biochemical know how gained from the mass of p53 research to further elucidate ΔΝp63α gene function? In this review, we will summarise the emerging advances that are elucidating ΔΝp63α as a promising drug target.
Authors
Lee E. Finlan
The University of Edinburgh, Edinburgh, UK
Ted R. Hupp
The University of Edinburgh
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.