Research Systems Biology

p53, the cancer killer

Cancer is a very serious condition that unfortunately is still fatal in a vast majority of cases. One of the reasons for not having yet more effective treatments relies on the great complexity of the problem.

Every single day, the DNA of each cell is mutated thousands of times, even in the absence of oncogenes or extreme radiation. Many of these mutations could lead to cancer and, finally, death.

At the center of the defense machinery of multicellular organisms against potentially fatal cellular stresses is the p53 protein. This protein is a transcription factor and controls a great number of key cellular functions. The whole network includes a few hundred proteins and microRNAs and is still a widely open and unresolved problem.

An intact p53 network guarantees that DNA damage is detected, and if possible corrected, early on. The importance of p53 for preventing cancer relates to the fact that p53 is inactivated in more than 50% of all human cancers.

The great complexity of the "cancer network", as shown below, resembles more an electronic circuit or the control system of an industrial plant. Consequently, it can be expected that tools developed by engineers during the past century can readily be applied to study complex biologic systems.

p53_network.png

Systems Biology is a modern research area that includes systems and control theories. These theories are very convenient to analyze the oscillatory behavior of the concentrations of p53 and MDM2 proteins, for example.

p53_control.png

For a brief discusion of some models used for the p53 network, you can click here (in Spanish).

References

1. Gironella et. al, PNAS (2007) 104, 16170
2. Kohn and Pommier, Biochem. Biophys. Res. Commun. (2005) 331, 816
3. Ogunnaike, J. R. Soc. Interface (2006) 3, 175
4. Romer, Klein, Dehner, Kessler, Buchner, Angew. Chem. Int. Ed. (2006) 45, 6440

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