Wu Meng-Hsun, Huang Chi-Jung, Liu Shu-Ting, Liu Pei-Yao, Ho Ching-Liang, Huang Shih-Ming
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei City 114, Taiwan, ROC.
Biochem Biophys Res Commun. 2007 May 11;356(3):523-8. doi: 10.1016/j.bbrc.2007.02.162. Epub 2007 Mar 12.
In addition to the human papillomavirus (HPV)-induced immortalization of epithelial cells, which usually requires integration of the viral DNA into the host cell genome, steroid hormone-activated nuclear receptors (NRs) are thought to bind to specific DNA sequences within transcriptional regulatory regions on the long control region to either increase or suppress transcription of dependent genes. In this study, our data suggest that the NR coactivator function of HPV E2 proteins might be mediated through physical and functional interactions with not only NRs but also the NR coactivators GRIP1 (glucocorticoid receptor-interacting protein 1) and Zac1 (zinc-finger protein which regulates apoptosis and cell cycle arrest 1), reciprocally regulating their transactivation activities. GRIP1 and Zac1 both were able to act synergistically with HPV E2 proteins on the E2-, androgen receptor-, and estrogen receptor-dependent transcriptional activation systems. GRIP1 and Zac1 might selectively function with HPV E2 proteins on thyroid receptor- and p53-dependent transcriptional activation, respectively. Hence, the transcriptional function of E2 might be mediated through NRs and NR coactivators to regulate E2-, NR-, and p53-dependent transcriptional activations.
除了人乳头瘤病毒（HPV）诱导上皮细胞永生化（通常需要病毒DNA整合到宿主细胞基因组中）外，类固醇激素激活的核受体（NRs）被认为可与长控制区转录调控区域内的特定DNA序列结合，从而增加或抑制相关基因的转录。在本研究中，我们的数据表明，HPV E2蛋白的NR共激活因子功能可能不仅通过与NRs的物理和功能相互作用介导，还通过与NR共激活因子GRIP1（糖皮质激素受体相互作用蛋白1）和Zac1（调节细胞凋亡和细胞周期阻滞的锌指蛋白1）的相互作用介导，相互调节它们的反式激活活性。GRIP1和Zac1都能够在E2、雄激素受体和雌激素受体依赖性转录激活系统上与HPV E2蛋白协同作用。GRIP1和Zac1可能分别在甲状腺受体和p53依赖性转录激活上与HPV E2蛋白选择性发挥作用。因此，E2的转录功能可能通过NRs和NR共激活因子介导，以调节E2、NR和p53依赖性转录激活。
