Münger K, Werness B A, Dyson N, Phelps W C, Harlow E, Howley P M
Laboratory of Tumor Virus Biology, National Cancer Institute, Bethesda, MD 20892.
EMBO J. 1989 Dec 20;8(13):4099-105. doi: 10.1002/j.1460-2075.1989.tb08594.x.
The E7 proteins encoded by the human papillomaviruses (HPVs) associated with anogenital lesions share significant amino acid sequence homology. The E7 proteins of these different HPVs were assessed for their ability to form complexes with the retinoblastoma tumor suppressor gene product (p105-RB). Similar to the E7 protein of HPV-16, the E7 proteins of HPV-18, HBV-6b and HPV-11 were found to associate with p105-RB in vitro. The E7 proteins of HPV types associated with a high risk of malignant progression (HPV-16 and HPV-18) formed complexes with p105-RB with equal affinities. The E7 proteins encoded by HPV types 6b and 11, which are associated with clinical lesions with a lower risk for progression, bound to p105-RB with lower affinities. The E7 protein of the bovine papillomavirus type 1 (BPV-1), which does not share structural similarity in the amino terminal region with the HPV E7 proteins, was unable to form a detectable complex with p105-RB. The amino acid sequences of the HPV-16 E7 protein involved in complex formation with p105-RB in vitro have been mapped. Only a portion of the sequences that are conserved between the HPV E7 proteins and AdE1A were necessary for association with p105-RB. Furthermore, the HPV-16 E7-p105-RB complex was detected in an HPV-16-transformed human keratinocyte cell line.
与肛门生殖器病变相关的人乳头瘤病毒（HPV）所编码的E7蛋白具有显著的氨基酸序列同源性。对这些不同HPV的E7蛋白与视网膜母细胞瘤肿瘤抑制基因产物（p105-RB）形成复合物的能力进行了评估。与HPV-16的E7蛋白相似，HPV-18、HPV-6b和HPV-11的E7蛋白在体外被发现可与p105-RB结合。与恶性进展高风险相关的HPV类型（HPV-16和HPV-18）的E7蛋白以相同亲和力与p105-RB形成复合物。与进展风险较低的临床病变相关的HPV 6b型和11型所编码的E7蛋白以较低亲和力与p105-RB结合。牛乳头瘤病毒1型（BPV-1）的E7蛋白在氨基末端区域与HPV E7蛋白没有结构相似性，无法与p105-RB形成可检测到的复合物。已确定了HPV-16 E7蛋白在体外与p105-RB形成复合物所涉及的氨基酸序列。HPV E7蛋白和腺病毒E1A之间保守的序列中只有一部分对于与p105-RB结合是必需的。此外，在HPV-16转化的人角质形成细胞系中检测到了HPV-16 E7-p105-RB复合物。
