Mutations activating the PI3K (phosphoinositide 3-kinase)/Akt signalling pathway and inactivating the TP53 tumour-suppressor gene are common mechanisms that cancer cells require to proliferate and escape pre-programmed cell death. In a well-described mechanism, Akt mediates negative control of p53 levels through enhancing MDM2 (murine double minute 2)-mediated targeting of p53 for degradation. Accumulating evidence is beginning to suggest that, in certain circumstances, PTEN (phosphatase and tensin homologue deleted on chromosome 10)/PI3K/Akt also promotes p53 translation and protein stability, suggesting that additional mechanisms may be involved in the Akt-mediated regulation of p53 in tumours. In the present article, we discuss these aspects in the light of clinical PI3K/Akt inhibitors, where information regarding the effect on p53 activity will be a crucial factor that will undoubtedly influence therapeutic efficacy.
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Conference Article|
August 11 2014
PI3K/Akt-mediated regulation of p53 in cancer
Aswin G. Abraham;
Aswin G. Abraham
*Cancer Research UK/MRC Oxford Institute, Gray Laboratories, Department of Oncology, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, U.K.
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Eric O’Neill
Eric O’Neill
1
*Cancer Research UK/MRC Oxford Institute, Gray Laboratories, Department of Oncology, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, U.K.
1To whom correspondence should be addressed (emaileric.oneill@oncology.ox.ac.uk).
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Publisher: Portland Press Ltd
Received:
March 31 2014
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2014 Biochemical Society
2014
Biochem Soc Trans (2014) 42 (4): 798–803.
Article history
Received:
March 31 2014
Citation
Aswin G. Abraham, Eric O’Neill; PI3K/Akt-mediated regulation of p53 in cancer. Biochem Soc Trans 1 August 2014; 42 (4): 798–803. doi: https://doi.org/10.1042/BST20140070
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