Role of a p53 polymorphism in the development of human papillomavirus-associated cancer.

Abstract:

:The E6 oncoprotein derived from tumour-associated human papillomaviruses (HPVs) binds to and induces the degradation of the cellular tumour-suppressor protein p53. A common polymorphism that occurs in the p53 amino-acid sequence results in the presence of either a proline or an arginine at position 72. The effect of this polymorphism on the susceptibility of p53 to E6-mediated degradation has been investigated and the arginine form of p53 was found to be significantly more susceptible than the proline form. Moreover, allelic analysis of patients with HPV-associated tumours revealed a striking overrepresentation of homozygous arginine-72 p53 compared with the normal population, which indicated that individuals homozygous for arginine 72 are about seven times more susceptible to HPV-associated tumorigenesis than heterozygotes. The arginine-encoding allele therefore represents a significant risk factor in the development of HPV-associated cancers.

journal_name

Nature

journal_title

Nature

authors

Storey A,Thomas M,Kalita A,Harwood C,Gardiol D,Mantovani F,Breuer J,Leigh IM,Matlashewski G,Banks L

doi

10.1038/30400

subject

Has Abstract

pub_date

1998-05-21 00:00:00

pages

229-34

issue

6682

eissn

0028-0836

issn

1476-4687

journal_volume

393

pub_type

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