Interaction between the HPV E7 oncoprotein and the transcriptional coactivator p300.
Oncogene
; 22(39): 7871-81, 2003 Sep 11.
Article
in En
| MEDLINE
| ID: mdl-12970734
ABSTRACT
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Nuclear Proteins
/
Trans-Activators
/
Oncogene Proteins, Viral
/
DNA-Binding Proteins
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Oncogene
Journal subject:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Year:
2003
Type:
Article
Affiliation country:
Italy