Physical and functional interactions of human papillomavirus E2 protein with nuclear receptor coactivators.
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.
Wu
Meng-Hsun
MH
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei City 114, Taiwan, ROC.
Huang
Chi-Jung
CJ
Liu
Shu-Ting
ST
Liu
Pei-Yao
PY
Ho
Ching-Liang
CL
Huang
Shih-Ming
SM
D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D016147:Genes, Tumor Suppressor; D006367:HeLa Cells; D052140:Human papillomavirus 11; D006801:Humans; D051379:Mice; D051958:Nuclear Receptor Coactivator 2 / Q000378:metabolism*; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism*
D018797:Cell Cycle Proteins; C117355:E2 protein, Human papillomavirus type 11; D051958:Nuclear Receptor Coactivator 2; D009856:Oncogene Proteins, Viral; C106464:PLAGL1 protein, human; C498423:Plagl1 protein, mouse; D011988:Receptors, Thyroid Hormone; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D014764:Viral Proteins; C069102:oncogene protein E2, Human papillomavirus type 18