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BK virus as a potential co-factor in human cancer
K F Harris1, E Chang, J B Christensen
1Graduate Program in Cellular and Molecular Biology, Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor 48109-0620, USA.
Developments in Biological Standardization
|October 17, 1998
Summary
BK virus (BKV) large T antigen interacts with tumor suppressor proteins, potentially driving cancer. This study reveals how BKV TAg inhibits DNA damage response and promotes cell growth, suggesting a role in human tumor formation.
Area of Science:
- Virology
- Oncology
- Molecular Biology
Background:
- BK virus (BKV), a polyomavirus, infects most humans and encodes a large T antigen (TAg) linked to transforming functions.
- BKV DNA has been detected in various human tumors, but its causative role in oncogenesis remains unclear.
Purpose of the Study:
- To investigate the molecular mechanisms of BKV-mediated cellular transformation.
- To characterize the interactions between BKV TAg and key cellular tumor suppressor proteins (p53, pRb, p107, p130).
Main Methods:
- Co-immunoprecipitation assays to assess protein-protein interactions.
- Functional assays to evaluate the impact of BKV TAg on cellular pathways.
Main Results:
- BKV TAg binds to and inhibits the function of p53, impairing the DNA damage response.
- Low levels of BKV TAg induce free E2F and a serum-independent cell phenotype, independent of pRb family interactions.
- BKV TAg demonstrates dual activity: inhibiting DNA damage response and promoting proliferation.
Conclusions:
- BKV TAg can disrupt cellular control mechanisms, leading to potential mutation accumulation.
- These findings suggest a plausible role for BKV TAg in human cellular transformation and tumor development.