Current advances in the inhibition of the auto-regulatory interaction between the p53 tumour suppressor protein and MDM2 protein

Picksley, S. M., Dart, Dafydd Alwyn, Mansoor, M.S. and Loadman, P.M. 2001. Current advances in the inhibition of the auto-regulatory interaction between the p53 tumour suppressor protein and MDM2 protein. Expert Opinion on Therapeutic Patents 11 (12) , pp. 1825-1835.

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Abstract

The p53 tumour suppressor protein is involved in co-ordinating the cellular response to genotoxic stress through initiating a G1-growth arrest and/or induction of apoptosis and thereby influences the success of most anticancer treatments. p53 is a damage-inducible transcription factor whose activity is negatively regulated by the binding of MDM2 protein. The ability to disrupt the p53-MDM2 regulatory loop has identified a novel therapeutic opportunity. Potent peptide inhibitors of the interaction between p53 and MDM2 protein have been identified, with IC50 values in the nanomolar range, and activate the p53-dependent stress response. Potentially, such peptides might have a wider application as non-genotoxic therapeutic p53 activators, in tumours that retain expression of wild type p53 protein, to induce the p53-dependent apoptotic pathway.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Publisher:	Informa Healthcare
ISSN:	1354-3776
Last Modified:	08 Jan 2020 03:29
URI:	https://orca.cardiff.ac.uk/id/eprint/50281

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