Zerfass-Thome K, Zwerschke W, Mannhardt B, Tindle R, Botz J W, Jansen-Dürr P
Deutsches Krebsforschungszentrum, Forschungsschwerpunkt Angewandte Tumorvirologie, Heidelberg, Germany.
Oncogene. 1996 Dec 5;13(11):2323-30.
Expression of the E7 oncogene of HPV-16 induces S phase entry of mammalian cells in the presence of antiproliferative signals. In particular, E7 can bypass G0/G1 arrest in response to both serum withdrawal and loss of cell adhesion, two experimental conditions in which cell cycle progression is accompanied by elevated levels of the cdk inhibitor p27KIP1. We show here that E7 can antagonize the ability of p27KIP1 to block cyclin E-associated kinase in vitro and to inhibit transcription from the cyclin A gene in transfection experiments. E7 associates with p27KIP1 both in a reconstituted in vitro system and in extracts of mammalian cells, and association requires the C-terminal part of E7. The interaction between p27KIP1 and E7 can also be demonstrated in a yeast two hybrid system. The data suggest that the ability of E7 to override certain forms of G0/G1 arrest is mediated in part by binding to and subsequent inactivation of the cdk inhibitor p27KIP1.
人乳头瘤病毒16型（HPV-16）E7癌基因的表达可使哺乳动物细胞在存在抗增殖信号的情况下进入S期。具体而言，E7能够绕过因血清剥夺和细胞黏附丧失所导致的G0/G1期阻滞，这两种实验条件下细胞周期进程伴随着细胞周期蛋白依赖性激酶抑制剂p27KIP1水平的升高。我们在此表明，E7在体外可拮抗p27KIP1阻断细胞周期蛋白E相关激酶的能力，并且在转染实验中可抑制细胞周期蛋白A基因的转录。在体外重建系统以及哺乳动物细胞提取物中，E7均与p27KIP1相结合，且这种结合需要E7的C末端部分。在酵母双杂交系统中也能够证实p27KIP1与E7之间的相互作用。这些数据表明，E7克服某些形式G0/G1期阻滞的能力部分是通过与细胞周期蛋白依赖性激酶抑制剂p27KIP1结合并使其失活来介导的。
