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The Epstein-Barr virus immediate-early protein BZLF1 regulates p53 function through multiple mechanisms
Amy Mauser1, Shin'ichi Saito, Ettore Appella
1Department of Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.
Journal of Virology
|November 20, 2002
Summary
Epstein-Barr virus protein BZLF1 activates infection but inhibits p53 function. This viral protein suppresses TATA binding protein (TBP) expression, partially explaining its effect on p53.
Area of Science:
- Virology
- Molecular Biology
- Cellular Biology
Background:
- Epstein-Barr virus (EBV) immediate-early protein BZLF1 regulates the switch between latent and lytic infection.
- BZLF1 is known to inhibit p53 transcriptional activity.
- Understanding BZLF1's mechanism is crucial for EBV infection control.
Purpose of the Study:
- To investigate the detailed effects of BZLF1 on p53 function.
- To elucidate the molecular mechanisms by which BZLF1 inhibits p53.
- To determine if BZLF1 affects p53 posttranslational modifications or DNA binding.
Main Methods:
- Utilized a BZLF1-expressing adenovirus vector (AdBZLF1) for cellular infection.
- Assessed p53-dependent gene induction (p21, MDM2).
- Performed electrophoretic mobility shift assays (EMSAs) for p53 DNA binding.
- Analyzed p53 phosphorylation and acetylation.
- Quantified cellular TATA binding protein (TBP) levels.
Main Results:
- AdBZLF1 infection increased cellular p53 levels but blocked p53 target gene induction.
- BZLF1 expression enhanced p53 DNA binding, phosphorylation, and acetylation.
- BZLF1 significantly reduced cellular TBP levels.
- Overexpression of TBP partially rescued BZLF1's inhibitory effect on p53.
Conclusions:
- BZLF1 inhibits p53 transcriptional function through mechanisms beyond p53 modification or DNA binding.
- BZLF1 suppresses TBP expression, suggesting an indirect pathway for p53 inhibition.
- BZLF1's interaction with TBP is a key factor in its disruption of p53 activity during EBV infection.