高危型人乳头瘤病毒16型的E5蛋白是否具有与牛乳头瘤病毒E5蛋白相同的转化特性？

Are transforming properties of the bovine papillomavirus E5 protein shared by E5 from high-risk human papillomavirus type 16?

作者信息

Suprynowicz Frank A, Disbrow Gary L, Simic Vera, Schlegel Richard

机构信息

Department of Pathology, Georgetown University Medical School, Preclinical Sciences Building, Room GR10C, 3900 Reservoir Road, NW, Box #571432, Washington, DC 20057, USA.

出版信息

Virology. 2005 Feb 5;332(1):102-13. doi: 10.1016/j.virol.2004.11.011.

DOI:10.1016/j.virol.2004.11.011

PMID:15661144

Abstract

The E5 proteins of bovine papillomavirus type 1 (BPV-1) and human papillomavirus type 16 (HPV-16) are small (44-83 amino acids), hydrophobic polypeptides that localize to membranes of the Golgi apparatus and endoplasmic reticulum, respectively. While the oncogenic properties of BPV-1 E5 have been characterized in detail, less is known about HPV-16 E5 due to its low expression in mammalian cells. Using codon-optimized HPV-16 E5 DNA, we have generated stable fibroblast cell lines that express equivalent levels of epitope-tagged BPV-1 and HPV-16 E5 proteins. In contrast to BPV-1 E5, HPV-16 E5 does not activate growth factor receptors, phosphoinositide 3-kinase or c-Src, and fails to induce focus formation, although it does promote anchorage-independent growth in soft agar. These variant activities are apparently unrelated to differences in intracellular localization of the E5 proteins since retargeting HPV-16 E5 to the Golgi apparatus does not induce focus formation.

摘要

1型牛乳头瘤病毒（BPV-1）和16型人乳头瘤病毒（HPV-16）的E5蛋白是小的（44 - 83个氨基酸）疏水性多肽，分别定位于高尔基体和内质网的膜上。虽然BPV-1 E5的致癌特性已得到详细表征，但由于其在哺乳动物细胞中表达水平较低，关于HPV-16 E5的了解较少。使用密码子优化的HPV-16 E5 DNA，我们构建了稳定的成纤维细胞系，这些细胞系表达等量的带有表位标签的BPV-1和HPV-16 E5蛋白。与BPV-1 E5不同，HPV-16 E5不激活生长因子受体、磷酸肌醇3激酶或c-Src，也不能诱导灶形成，尽管它确实能促进在软琼脂中的非锚定依赖性生长。这些不同的活性显然与E5蛋白在细胞内定位的差异无关，因为将HPV-16 E5重新定位到高尔基体并不能诱导灶形成。