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p53 can regulate numerous aspects of metabolic pathways and thereby influence the metabolic alterations exhibited by tumour cells. However, the contribution of p53 is complex and in some cases might promote, rather than inhibit, tumour progression. So, just what is p53 doing?
Mutant p53 proteins not only lose their tumour suppressive ability, but also gain new properties that promote tumorigenesis. What are these properties and what are the clinical implications?
How important is the DNA damage response in mobilizing the tumour suppression function of p53? This Review considers how supporting and conflicting evidence about the role of DNA damage response signalling in cancer can be reconciled.
Target response element sequences are a crucial part of the p53 network. This Review describes how functional response elements can be defined and discusses the implications of non-canonical p53 response elements, which greatly expand the universe of p53-regulated genes, on the part that p53 plays as a tumour suppressor.
The Rb–E2f and MDM2–p53 pathways are both defective in most human tumours, indicating that these pathways function independently in the control of cell fate. However, extensive crosstalk between these two pathways also exists. How do they coordinately affect tumour biology?
When p53 was first discovered, it received relatively little attention from cancer researchers. The road leading to p53's rise to fame, and the recognition ofTP53as the most frequently altered gene in human cancer, has been long and winding. This Timeline examines the rich history of this pivotal tumour suppressor.
The selective pressures for the retention of primordial p53 genes predated the appearance of cancer. Therefore, wild-type tumour suppressive functions were probably co-opted from unrelated primordial activities. Is it possible to deduce what these early functions might have been?
To celebrate the past 30 years of research on p53 this Focus issue of specially-commissioned articles reflects the history and emerging directions that will be important for future research on this multi-talented protein.
