Role of a p53 polymorphism in the development of human papillomavirus-associated cancer.
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.
Storey
A
A
Imperial Cancer Research Fund, Skin Tumour Laboratory, London, UK.
Thomas
M
M
Kalita
A
A
Harwood
C
C
Gardiol
D
D
Mantovani
F
F
Breuer
J
J
Leigh
I M
IM
Matlashewski
G
G
Banks
L
L
D000483:Alleles; D001120:Arginine / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000821:virology; D004268:DNA-Binding Proteins; D004198:Disease Susceptibility; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D027383:Papillomaviridae / Q000502:physiology*; D030361:Papillomavirus Infections / Q000235:genetics*; D011110:Polymorphism, Genetic; D012097:Repressor Proteins; D012878:Skin Neoplasms / Q000235:genetics / Q000821:virology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D014412:Tumor Virus Infections / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism / Q000821:virology
D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; C052603:E6 protein, Human papillomavirus type 18; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; D001120:Arginine