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Published on: August 4, 2019
Polyomavirus large T antigen overcomes p53 dependent growth arrest
1Molecular and Cell Biology Program, University of Maryland at Baltimore, 21201, USA.
Oncogene
|April 24, 1997
Summary
Polyomavirus large T antigen overcomes p53-mediated cell cycle arrest by interacting with the retinoblastoma protein (pRB). This viral protein bypasses the tumor suppressor function of p53, promoting cell proliferation.
Area of Science:
- Oncology
- Virology
- Molecular Biology
Background:
- Polyomavirus oncogenesis occurs independently of p53 tumor suppressor protein.
- Cell cycle regulation is crucial for preventing uncontrolled cell proliferation and tumor formation.
Purpose of the Study:
- To investigate how polyomavirus T antigens circumvent the growth-suppressive activity of p53.
- To determine the role of retinoblastoma protein (pRB) interaction in this process.
Main Methods:
- Utilized temperature-sensitive p53 in p53-null mouse embryo fibroblasts to control p53 function.
- Introduced polyomavirus large T (LT) and middle T (MT) antigens into these cells.
- Assessed cell cycle arrest, p21/WAF1 induction, and pRB phosphorylation in response to p53 and T antigen expression.
Main Results:
- Functional p53 induced G1/G0 arrest and p21/WAF1 expression.
- Polyomavirus LT antigen, but not MT antigen, overcame p53-induced cell cycle arrest.
- LT-mediated rescue of proliferation required pRB binding, as a mutant LT lacking this ability failed to override p53 function.
- LT promoted pRB phosphorylation even in the presence of p21/WAF1.
Conclusions:
- Polyomavirus LT antigen interferes with p53's growth-suppressive activity through interaction with pRB.
- This interaction is essential for overcoming p53-dependent cell cycle arrest and promoting viral oncogenesis.
- LT antigen bypasses p53's tumor suppressor function by modulating pRB activity.
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