J. Cancer Mol. 2: 141-153, 2006

[Review Article]

p53: Structure, Function and Therapeutic Applications 

Ling Bai and Wei-Guo Zhu

Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, China [L. Bai, W.-G. Zhu]; Department of Biotechnology, Guilin Medical College, Guilin, China [L. Bai]

Abstract:

Since the p53 tumor suppressor gene has been found to be mutated in more than 50% of human cancers, it has attracted the interest of numerous researchers.  The capacity of p53 for multiple biological functions can be attributed to its ability to act as a sequence-specific transcription factor to regulate expression of over one hundred different targets, and thus to modulate various cellular processes including apoptosis, cell cycle arrest and DNA repair.  The p53 protein with its unique C- and N-terminal structures is rigidly modulated by several important biological processes such as phosphorylation, acetylation and ubiquitination, through which it effectively regulates cell growth and cell death.  p53 mutations can lead either to loss or change of p53 binding activity to its downstream targets and may thus induce aberrant cell proliferation, with consequent malignant cellular transformation.  Based on p53’s critical role in carcinogenesis, scientists have developed multiple effective strategies for treating cancer by enhancing function of wild-type p53 or increasing p53 stability.  This review will focus on (i) discussing of the relationship between p53 structure and function, (ii) p53 mutations, and (iii) recent strategies for improving the efficacy of cancer treatment by therapeutic manipulation of p53.

Received 6/20/06; Revised 7/30/06; Accepted 7/31/06.

¹Correspondence: Dr. Wei-Guo Zhu, Department of Biochemistry and Molecular Biology, Beijing University Health Science Center, No. 38, Xueyuan Road, Beijing, 100083, China. Phone: 86-10-8280 2235. Fax: 86-10-8280 5079. Email: zhuweiguo@bjmu.edu.cn

²Abbreviations: SV40, simian virus 40; wt p53, wild-type p53; mt p53, mutated p53; MDM2, murine double minute 2; DSBs, double strand breaks in DNA; ATM, ataxia-telangiectasia mutated protein; ATR, ATM and Rad3-related protein; Gadd45, growth arrest and DNA-damage-inducible protein 45; CDK, cyclin-dependent kinase; Bax, Bcl-2-associated X protein; DR5, death receptor 5; PIG3, p53-inducible gene 3; Puma, p53-upregulated modulator of apoptosis; PIDD, p53-induced protein with death domain; PERP, p53 apoptosis effector related to PMP-22; Apaf-1, apoptotic protease-activating factor-1; p53AIP1, p53-regulated apoptosis-inducing protein 1; Bid, BH3-interacting death agonist; 5-FU, 5-fluorouracil; IAPs, inhibitor of apoptosis proteins; TRAIL, tumor necrosis factor-related apoptosis-inducing ligand; ASPP, Apoptotic-Stimulating Protein of p53; HDAC1, histone deacetylase 1; PML, promyelocytic leukaemia protein; YY1, Yin Yang 1; PLD, phospholipase D; HATs, histone acetyltransferases; PCAF, p300/CBP-associated factor; SSDB, sequence-specific DNA binding; APC, adenomatosis polyposis coli protein; HPV, human papilloma virus; PRIMA, p53 reactivation and induction of massive apoptosis.