Interaction between the HPV E7 oncoprotein and the transcriptional coactivator p300.
Infection with high-risk human papillomaviruses (HPV) can lead to the development of cervical cancer. This process depends on the interaction of the virus-encoded oncoproteins, E6 and E7, with a variety of host regulatory proteins. As E7 shares both functional and structural similarities with the Adenovirus E1a (Ad E1a) protein, we were interested in investigating the possible interactions between E7 and the transcriptional coactivator p300, since it was originally identified as a target of Ad E1a. Using a variety of assays, we show that E7s from both high- and low-risk HPV types interact with p300. Mutational analysis of E7 maps the site of the interaction to a region spanning the pRb-binding domain and the CKII phosphorylation site. We also map the site of interaction on p300 largely to the CH1 domain. In addition, we demonstrate that the binding between 16E7 and p300 is direct, and can be detected in vivo by coimmunoprecipitation and mammalian two-hybrid assays. Finally, we show that E7 can abolish the p300-mediated E2 transactivation function, suggesting that complex formation between E7 and p300 may contribute to the regulation of E2 transcriptional activity.
Bernat
Agnieszka
A
International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I-34012 Trieste, Italy.
Avvakumov
Nikita
N
Mymryk
Joe S
JS
Banks
Lawrence
L
D000818:Animals; D001665:Binding Sites; D047390:Casein Kinase II; D022003:Cell Nucleus Structures / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D050881:E1A-Associated p300 Protein; D006801:Humans; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D050725:Papillomavirus E7 Proteins; D010766:Phosphorylation; D011233:Precipitin Tests; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D020798:Two-Hybrid System Techniques
D004268:DNA-Binding Proteins; C054855:E2 protein, Human papillomavirus type 16; D009687:Nuclear Proteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D015534:Trans-Activators; C059731:oncogene protein E7, Human papillomavirus type 16; D050881:E1A-Associated p300 Protein; C494362:Ep300 protein, rat; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases