Kukimoto I, Aihara S, Yoshiike K, Kanda T
Division of Molecular Genetics, National Institute of Infectious Diseases, Tokyo, Japan.
Biochem Biophys Res Commun. 1998 Aug 10;249(1):258-62. doi: 10.1006/bbrc.1998.9066.
Oncoprotein E6 of the human papillomavirus (HPV) associated with cervical cancer (HPV-16 and -18) degrades tumor suppressor protein p53, but seems to have p53-independent transforming functions. We searched for other cellular targets for the N-terminal region of HPV-16 E6 using a yeast two-hybrid system. The E6 was found to bind to the C-terminal region of a human minichromosome maintenance 7 (hMCM7) protein, which is a component of replication licensing factors. The full-length hMCM7 translated in vitro was capable of binding to bacterially expressed E6. In yeast cells the E6s of the cancer-associated HPVs (HPV-16, -18, and -58) bound to hMCM7 more strongly than those of the HPVs associated with a benign tumor (HPV-6 and -11). Binding of E6 with hMCM7 may cause chromosomal abnormalities found in the human cells expressing E6s of oncogenic HPVs.
与宫颈癌相关的人乳头瘤病毒(HPV-16和-18)的癌蛋白E6可降解肿瘤抑制蛋白p53,但似乎具有不依赖p53的转化功能。我们使用酵母双杂交系统寻找HPV-16 E6 N端区域的其他细胞靶点。发现E6可与人微小染色体维持蛋白7(hMCM7)的C端区域结合,hMCM7是复制许可因子的一个组成部分。体外翻译的全长hMCM7能够与细菌表达的E6结合。在酵母细胞中,与癌症相关的HPV(HPV-16、-18和-58)的E6与hMCM7的结合比与良性肿瘤相关的HPV(HPV-6和-11)的E6更强。E6与hMCM7的结合可能导致在表达致癌HPV E6的人类细胞中发现的染色体异常。