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The human papillomavirus type 16 E7 gene product interacts with and trans-activates the AP1 family of transcription factors
Author(s): Antinore MJ, Birrer MJ, Patel D, Nader L, McCance DJ
Source: EMBO JOURNAL    Volume: 15    Issue: 8    Pages: 1950-1960    Published: APR 15 1996  
Times Cited: 125     References: 72     
Abstract: The E7 gene product of human papillomavirus type 16 (HPV16) binds to the retinoblastoma gene product (pRb) and dissociates pRb-E2F complexes. However, the observation that the ability of E7 to bind pRb is not required for the HPV16-induced immortalization of primary keratinocytes prompted a search for other cellular factors bound by E7. Using a glutathione-S-transferase (GST) fusion protein system, we show that E7 complexes with AP1 transcription factors including c-Jun, JunB, JunD and c-Fos. The ability of E7 to complex with c-Jun in vivo is demonstrated by co-immunoprecipitation and the yeast two-hybrid system. An analysis of E7 point mutants in the GST system indicates that the E7 zinc-finger motif, but not the pRb binding domain, is involved in these interactions. Using c-Jun deletion mutants, E7 binding maps between amino acids 224 and 286 of c-Jun. E7 trans-activates c-Jun-induced transcription from a Jun responsive promoter, and this activity correlates with the ability of E7 mutants to bind Jun proteins. Finally, a transcriptionally inactive c-Jun deletion, which can bind E7, interferes with the E7-induced transformation of rat embryo fibroblasts in cooperation with an activated ras, indicating that the Jun-E7 interaction is physiologically relevant and that Jun factors may be targeted in the E7 transformation pathway.
Document Type: Article
Language: English
Addresses:
1. UNIV ROCHESTER, DEPT MICROBIOL & IMMUNOL, ROCHESTER, NY 14642 USA
2. NCI, BIOMARKERS & PREVENT RES BRANCH, DIV CANC PREVENT & CONTROL, ROCKVILLE, MD 20850 USA
Publisher: OXFORD UNIV PRESS UNITED KINGDOM, WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP
Subject Category: Biochemistry & Molecular Biology; Cell Biology
IDS Number: UG748
ISSN: 0261-4189
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