Clues in the p53 murder mystery

Access through your institution Buy or subscribe Understanding the elements in this connection would give insight into the mode of action of ionizing radiation and many drugs used in cancer

therapy. Further, there is some — albeit incomplete — evidence that, through this function, p53 commits to death those cells that have sustained DNA damage from mutagens, so purging tissues

of the founder cells of cancer2,3. p53 is also apparently responsible for cell deletion following hypoxia4. Mechanistically, this might be merely a restatement of the theme of DNA damage,

because hypoxia, particularly if it is of fluctuating extent, can lead to bursts of production of reactive oxygen species (ROS), which in turn can engender DNA strand breaks. Conceptually,

however, it raises the possibility that pharmacological regulation of p53 action might significantly modify the extent of hypoxic tissue injury in myocardial infarction and stroke5. Death is

not the only possible outcome of p53 expression after a cell has been injured. In many circumstances, defined in part by cell lineage but also by other, ill-understood factors, the injured

cells survive, but are retained in the G1 phase of the cell cycle, sometimes for long periods6. The basis for this arrest is induction by p53 of the cyclin kinase inhibitor p21 _waf-1_ .

Results from p21 knockout animals and other experiments, however, show unequivocally that p21 is not required for post-injury, p53-dependent apoptosis7,8. This implies that, downstream of

p53 activation, there is a means of making the ultimate choice between life and death, but the molecular basis of this choice is enigmatic9. This is a preview of subscription content, access

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Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES * Polyak, K., Xia, Y., Zweier, J. L., Kinzler, K. W. & Vogelstein, B. _Nature_ 389,

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Israeli, D. _et al. EMBO J._ 16, 4384–4392 (1997). Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * the Sir Alastair Currie CRC Laboratories, University of

Edinburgh, Western General Hospital, Crewe Road, EH4 2XU, Edinburgh, UK Andrew Wyllie Authors * Andrew Wyllie View author publications You can also search for this author inPubMed Google

Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Wyllie, A. Clues in the p53 murder mystery. _Nature_ 389, 237–238 (1997).

https://doi.org/10.1038/38405 Download citation * Issue Date: 18 September 1997 * DOI: https://doi.org/10.1038/38405 SHARE THIS ARTICLE Anyone you share the following link with will be able

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