Chapter category: Oncogenes

The p53-Mdm2 Loop A Critical Juncture of Stress Response

This chapter appears in the following book:

p53

Edited by: Theodore Hupp and Ayeda Ayed
ISBN: TBA141
» Get more information about this book at landesbioscience.com «

Chapter authors:
Zehavit Goldberg, Igal Louria-Hayon, Tamar Grossman, Michael Berger and Ygal Haupt

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The presence of a functional p53 protein is a key factor for the proper suppression of cancer development. A loss of p53 activity, by mutations or inhibition, is often associ ated with human malignancies. The p53 protein integrates various stress signals into a growth restrictive cellular response. In this way, p53 eliminates cells with a potential to become cancerous. Being a powerful decision maker, it is imperative that p53 will be activated properly, efficiently and temporarily in response to stress. Equally important is that p53 activation will be extinguished upon recovery from stress, and that false activation of p53 will be avoided. Failure to achieve these aims is likely to have catastrophic consequences for the organism. The machinery that governs this tight regulation is largely based on the major inhibitor of p53, Mdm2, which both blocks p53 activities and promotes its destabilization. The interplay between p53 and Mdm2 involves a complex network of positive and negative feedback loops. Relief from Mdm2 suppression is required for p53 to be stabilized and activated in response to stress. Protection from Mdm2 entails a concerted action of modifying enzymes and partner proteins. The association of p53 with the PML-nuclear bodies may provide an infrastructure in which this complex regulatory network can be orchestrated. In this chapter we use examples to illustrate the regulatory machinery that drives this network.

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Chapter category: Oncogenes

The p53-Mdm2 Loop A Critical Juncture of Stress Response

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