Inactivation of the cdk inhibitor p27KIP1 by the human papillomavirus type 16 E7 oncoprotein.
Inactivation of the cdk inhibitor p27KIP1 by the human papillomavirus type 16 E7 oncoprotein.
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发表时间：
1996-12
期刊：
影响因子：
8
通讯作者：
K. Zerfass-Thome;W. Zwerschke;B. Mannhardt;R. Tindle;Botz Jw;P. Jansen-Dürr
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文献类型：
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作者：
K. Zerfass-Thome;W. Zwerschke;B. Mannhardt;R. Tindle;Botz Jw;P. Jansen-Dürr
HPV-16 的 E7 癌基因的表达在存在抗增殖信号的情况下诱导哺乳动物细胞进入 S 期。特别是，E7 可以绕过 G0/G1 停滞，以响应血清撤退和细胞粘附丧失，这两种实验条件下细胞周期进展伴随着 cdk 抑制剂 p27KIP1 水平的升高。我们在此表明，E7 可以拮抗 p27KIP1 在体外阻断细胞周期蛋白 E 相关激酶的能力，并在转染实验中抑制细胞周期蛋白 A 基因转录的能力。 E7 在体外重建系统和哺乳动物细胞提取物中均与 p27KIP1 结合，并且结合需要 E7 的 C 末端部分。 p27KIP1 和 E7 之间的相互作用也可以在酵母二杂交系统中得到证明。数据表明，E7 克服某些形式的 G0/G1 停滞的能力部分是通过与 cdk 抑制剂 p27KIP1 结合并随后使其失活来介导的。
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.