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Role of a p53 polymorphism in the development of human papillomavirus-associated cancer (see comments)

机译:p53基因多态性在人类乳头瘤病毒相关癌症发展中的作用(见评论)

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摘要

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.
机译:源自与肿瘤相关的人乳头瘤病毒(HPV)的E6癌蛋白与细胞肿瘤抑制蛋白p53结合并诱导其降解。 p53氨基酸序列中常见的多态性导致72位脯氨酸或精氨酸的存在。已经研究了该多态性对p53对E6介导的降解的敏感性的影响,并且精氨酸形式为发现p53比脯氨酸形式更易感。此外,对HPV相关肿瘤患者的等位基因分析显示,与正常人群相比,纯合精氨酸-72 p53显着过高,这表明精氨酸72纯合子的人与HPV相关肿瘤发生的敏感性是杂合子的七倍。因此,精氨酸编码等位基因代表了与HPV相关的癌症发展中的重要危险因素。

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