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PMID: 11062053 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

Strategies for manipulating the p53 pathway in the treatment of human cancer.

The Biochemical journal ·Vol. 352 Pt 1 ·2000-11-15 ·Pages 1-17

Hupp TR, Lane DP, Ball KL

Abstract

Human cancer progression is driven in part by the mutation of oncogenes and tumour-suppressor genes which, under selective environmental pressures, give rise to evolving populations of biochemically altered cells with enhanced tumorigenic and metastatic potential. Given that human cancers are biologically and pathologically quite distinct, it has been quite surprising that a common event, perturbation of the p53 pathway, occurs in most if not all types of human cancers. The central role of p53 as a tumour-suppressor protein has fuelled interest in defining its mechanism of function and regulation, determining how its inactivation facilitates cancer progression, and exploring the possibility of restoring p53 function for therapeutic benefit. This review will highlight the key biochemical properties of p53 protein that affect its tumour-suppressor function and the experimental strategies that have been developed for the re-activation of the p53 pathway in cancers.

MeSH Terms
Animals Apoptosis Genes, p53/genetics Humans Mice Models, Biological Mutation Neoplasms/drug therapy Nuclear Proteins Protein Conformation Protein Structure, Tertiary Proto-Oncogene Proteins/metabolism Proto-Oncogene Proteins c-mdm2 Signal Transduction Transcription, Genetic Transcriptional Activation Tumor Suppressor Protein p53/chemistry,metabolism,physiology
Chemicals
Nuclear Proteins Proto-Oncogene Proteins Tumor Suppressor Protein p53 MDM2 protein, human Mdm2 protein, mouse Proto-Oncogene Proteins c-mdm2
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Hupp T R
Cancer Research Campaign Laboratories, Department of Molecular and Cellular Pathology, University of Dundee Medical School, Dundee DD1 9SY, Scotland, UK. [email protected]
Lane D P
Ball K L
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
Email
[email protected]
Published
2000-11-15
Pages
1-17
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1221427
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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