The p53-Mdm2 loop: A critical juncture of stress response

36Citations
Citations of this article
28Readers
Mendeley users who have this article in their library.
Get full text

Abstract

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 associated 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 improper 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.

References Powered by Scopus

Surfing the p53 network

6052Citations
N/AReaders
Get full text

Mdm2 promotes the rapid degradation of p53

3936Citations
N/AReaders
Get full text

Regulation of p53 stability by Mdm2

2949Citations
N/AReaders
Get full text

Cited by Powered by Scopus

Targeting oncogenic mutant p53 for cancer therapy

274Citations
N/AReaders
Get full text

Degradation of proteins by PROTACs and other strategies

216Citations
N/AReaders
Get full text

DNAJA1 controls the fate of misfolded mutant p53 through the mevalonate pathway

186Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Levav-Cohen, Y., Goldberg, Z., Tan, K. H., Alsheich-Bartok, O., Zuckerman, V., Haupt, S., & Haupt, Y. (2014). The p53-Mdm2 loop: A critical juncture of stress response. Sub-Cellular Biochemistry, 85, 161–186. https://doi.org/10.1007/978-94-017-9211-0_9

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 9

69%

Professor / Associate Prof. 2

15%

Researcher 2

15%

Readers' Discipline

Tooltip

Biochemistry, Genetics and Molecular Bi... 8

44%

Agricultural and Biological Sciences 4

22%

Medicine and Dentistry 4

22%

Immunology and Microbiology 2

11%

Save time finding and organizing research with Mendeley

Sign up for free