Tumour suppression by p53: a role for the DNA damage response?
Loss of p53 function occurs during the development of most, if not all, tumour types. This paves the way for genomic instability, tumour-associated changes in metabolism, insensitivity to apoptotic signals, invasiveness and motility. However, the nature of the causal link between early tumorigenic events and the induction of the p53-mediated checkpoints that constitute a barrier to tumour progression remains uncertain. This Review considers the role of the DNA damage response, which is activated during the early stages of tumour development, in mobilizing the tumour suppression function of p53. The relationship between these events and oncogene-induced p53 activation through the ARF pathway is also discussed.
Meek
David W
DW
Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK. d.w.meek@dundee.ac.uk
D004249:DNA Damage / Q000502:physiology*; D006801:Humans; D009369:Neoplasms / Q000378:metabolism*; D015398:Signal Transduction; D025803:Tumor Suppressor Protein p14ARF / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53