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Complementation of a p300/CBP defective-binding mutant of adenovirus E1a by human papillomavirus E6 proteins
Agnieszka Bernat1, Paola Massimi1, Lawrence Banks1
1International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I-34012 Trieste, Italy1.
Abstract:
Previous studies have shown that the human papillomavirus type 16 (HPV-16) E6 protein binds to p300/CBP and abrogates its transcriptional co-activator function. However, there is little information on the biological consequences of this interaction and discrepancy as to whether the interaction is high-risk E6 specific or not. We performed a series of studies to compare the interactions of HPV-18 and HPV-11 E6 with p300, and showed that both high- and low- risk E6 proteins bind p300. In addition, using a transformation-deficient mutant of adenovirus E1a, which cannot interact with p300, we demonstrated that HPV-16, HPV-18 and, to a lesser extent, HPV-11 E6, can complement this mutant in cell transformation assays. In contrast, a mutant of HPV-16 E6 which does not bind p300 failed to rescue the E1a mutant. These results suggest that the E6-p300 interaction may be important for the ability of HPV E6 to contribute towards cell transformation.
Insights
Human papillomavirus (HPV) E6 proteins from both high-risk and low-risk types bind to the p300 co-activator. This interaction is crucial for HPV E6
Area of Science:
- Oncology
- Virology
- Molecular Biology
Background:
- The human papillomavirus (HPV) type 16 E6 protein interacts with p300/CBP, inhibiting its transcriptional co-activator function.
- Limited data exists on the biological impact of this interaction and whether it is specific to high-risk HPV E6 proteins.
Purpose of the Study:
- To investigate the interaction of HPV-18 and HPV-11 E6 proteins with p300.
- To determine the role of the E6-p300 interaction in HPV-mediated cell transformation.
Main Methods:
- Comparative analysis of E6 protein interactions with p300 across different HPV types (HPV-16, HPV-18, HPV-11).
- Cell transformation assays using a transformation-deficient adenovirus E1a mutant complemented by various HPV E6 proteins and mutants.
- Assessment of HPV-16 E6 mutant lacking p300 binding capability in complementing the E1a mutant.
Main Results:
- Both high-risk (HPV-16, HPV-18) and low-risk (HPV-11) E6 proteins bind to p300.
- HPV-16, HPV-18, and HPV-11 E6 proteins could complement the transformation-deficient adenovirus E1a mutant.
- An HPV-16 E6 mutant that does not bind p300 failed to rescue the E1a mutant's transformation deficiency.
Conclusions:
- The E6-p300 interaction is not exclusive to high-risk HPV types.
- The interaction between HPV E6 proteins and p300 plays a significant role in facilitating cell transformation by HPV E6.