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Blockage by adenovirus E4orf6 of transcriptional activation by the p53 tumor suppressor
T Dobner1, N Horikoshi, S Rubenwolf
1Institut für Medizinische Mikrobiologie und Hygiene, Universität Regensburg, Germany.
Abstract:
The adenovirus E4orf6 protein is shown here to interact with the cellular tumor suppressor protein p53 and to block p53-mediated transcriptional activation. The adenovirus protein inhibited the ability of p53 to bind to human TAFII31, a component of transcription factor IID (TFIID). Earlier work demonstrated that the interaction of p53 with TAFII31 involves a sequence near the NH2-terminus of p53, whereas the E4orf6-p53 interaction occurs within amino acids 318 to 360 of p53. Thus, the E4orf6 protein interacts at a site on p53 distinct from the domain that binds to TAFII31 but nevertheless inhibits the p53-TAFII31 interaction.
Insights
Adenovirus E4orf6 protein binds to tumor suppressor p53, blocking its function. This interaction inhibits p53
Area of Science:
- Molecular Biology
- Virology
- Cancer Research
Background:
- The cellular tumor suppressor protein p53 plays a critical role in preventing cancer.
- Adenoviruses are viruses that can cause various illnesses.
- Understanding viral protein interactions with host cell machinery is key to antiviral strategies.
Purpose of the Study:
- To investigate the interaction between adenovirus E4orf6 protein and human p53.
- To determine the mechanism by which E4orf6 affects p53 transcriptional activity.
Main Methods:
- Co-immunoprecipitation assays to study protein-protein interactions.
- Analysis of p53-mediated transcriptional activation.
- Mapping of protein interaction domains.
Main Results:
- Adenovirus E4orf6 protein directly interacts with human p53.
- E4orf6 inhibits p53's ability to activate transcription.
- E4orf6 blocks p53 binding to TAFII31, a component of transcription factor IID (TFIID).
- The E4orf6 binding site on p53 is distinct from the TAFII31 binding site.
Conclusions:
- Adenovirus E4orf6 protein antagonizes the tumor suppressor function of p53.
- E4orf6 inhibits p53 transcriptional activity by interfering with its interaction with TFIID components.
- This viral interference mechanism may contribute to adenovirus-induced oncogenesis.