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Interaction of adeno-associated virus Rep78 with p53: implications in growth inhibition
R B Batchu1, M A Shammas, J Y Wang
1Central Arkansas Veterans Health Care System and Myeloma and Transplantation Research Center, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
Abstract:
Adeno-associated virus (AAV) is a nonpathogenic, single-stranded DNA virus belonging to the parvoviridae family. Onco-suppressive properties of AAV against adenovirus, a DNA tumor virus, have been well documented. Rep78, a major regulatory protein of AAV, is believed to be responsible for its antioncogenic properties. Most DNA tumor viruses disturb the cell cycle pathways by essentially abrogating the functions of p53. Here we present evidence that AAV acts as an antiproliferative agent against adenovirus by protecting the adenoviral-mediated degradation of p53 as confirmed by both Western blot analysis and immunoprecipitation analysis with anti-p53 antibody. Coimmunoprecipitation experiments revealed that the AAV Rep78 is physically bound to p53 in vivo. Furthermore, the binding of purified p53 to the AAV Rep78 affinity column confirms their interaction. These results document for the first time that the antiproliferative effects of AAV against adenovirus are mediated, at least in part, by the interaction of AAV Rep78 with p53.
Insights
Adeno-associated virus (AAV) protects the tumor suppressor p53 from degradation by adenovirus. This interaction between AAV Rep78 protein and p53 mediates AAV's antiproliferative effects against adenovirus.
Area of Science:
- Virology
- Molecular Biology
- Oncology
Background:
- Adeno-associated virus (AAV) is a nonpathogenic parvovirus with documented oncosuppressive properties.
- DNA tumor viruses, like adenovirus, often disrupt cell cycle control by abrogating p53 function.
- The AAV Rep78 protein is implicated in AAV's antioncogenic activities.
Purpose of the Study:
- To investigate the mechanism by which AAV exerts antiproliferative effects against adenovirus.
- To determine if AAV Rep78 interacts with the p53 tumor suppressor protein.
Main Methods:
- Western blot analysis to assess p53 levels.
- Immunoprecipitation and coimmunoprecipitation assays to detect protein interactions.
- Affinity chromatography using purified p53 and AAV Rep78.
Main Results:
- AAV protects p53 from adenovirus-mediated degradation.
- AAV Rep78 protein physically binds to p53 in vivo.
- Purified p53 binds to AAV Rep78 in vitro, confirming direct interaction.
Conclusions:
- The antiproliferative action of AAV against adenovirus is, in part, mediated by the interaction between AAV Rep78 and p53.
- This study provides the first evidence of a direct molecular interaction between AAV Rep78 and p53.
- Understanding this interaction offers insights into viral oncogenesis and potential therapeutic strategies.