Interaction between the HPV-16 E2 transcriptional activator and p53

Area of Science:

• Virology
• Molecular Biology
• Cell Biology

Background:

• The human papillomavirus-16 E2 protein regulates viral DNA replication and gene expression.
• E2 interacts with E1 to localize it to replication origins and initiate viral DNA replication.
• E2 also induces apoptosis and cell cycle arrest, while p53 inhibits HPV DNA replication.

Purpose of the Study:

• To investigate the potential association between HPV-16 E2 protein and p53.
• To determine if p53 influences HPV DNA replication through interaction with E2.

Main Methods:

• In vitro binding assays to detect interactions between p53 and HPV-16 E2.
• Mutational analysis of p53 to identify interaction domains.
• Inducible p53 expression system to study complex formation in vivo.

Main Results:

• Specific interaction between p53 and HPV-16 E2 demonstrated in vitro via the carboxy-terminal half of E2.
• Both DNA binding and oligomerization domains of p53 are essential for E2 interaction.
• A p53 mutant unable to bind E2 lost its ability to inhibit HPV DNA replication.
• E2 complexes with p53 in vivo using an inducible expression system.

Conclusions:

• p53 directly interacts with HPV-16 E2 protein.
• This interaction is crucial for p53's inhibition of HPV DNA replication.
• p53 may be involved in HPV DNA replication centers, explaining E2's diverse cellular activities.