Induction of p53-independent apoptosis by simian virus 40 small t antigen

O Gjoerup1, D Zaveri, T M Roberts

  • 1Department of Cancer Biology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA.

Journal of Virology
|September 5, 2001
PubMed

Insights

Simian virus 40 small t antigen (st) can induce apoptosis in some cells, independent of p53. This cell death response is linked to st

Area of Science:

  • Virology
  • Cell Biology
  • Molecular Biology

Background:

  • Simian virus 40 small t antigen (st) is crucial for viral replication and cell transformation.
  • The precise role of st in cellular processes, particularly its potential to induce cell death, remains incompletely understood.

Purpose of the Study:

  • To investigate the capacity of Simian virus 40 small t antigen (st) to induce apoptosis in specific cell types.
  • To elucidate the mechanisms underlying st-induced apoptosis, including its relationship with p53 and protein phosphatase 2A (PP2A) binding.

Main Methods:

  • Transfection of human osteosarcoma (U2OS) and p53-deficient (H1299) cells with wild-type st and mutant forms.
  • Apoptosis assessment via nuclear morphology, TUNEL staining, and colony formation assays.
  • Analysis of st's interaction with PP2A in vivo and in vitro.
  • Evaluation of cell cycle progression using fluorescence-activated cell sorting (FACS).

Main Results:

  • Simian virus 40 small t antigen (st) induces apoptosis in U2OS and H1299 cells, characterized by nuclear fragmentation and DNA fragmentation.
  • Apoptosis induction by st is p53-independent.
  • Mutant st proteins (C103S and TR4) show altered apoptosis induction, with TR4 exhibiting impaired in vivo PP2A binding.
  • st expression inhibits colony formation, and this inhibition correlates with apoptosis levels.
  • Bcl-2 coexpression or caspase inhibition rescues cells from st-induced apoptosis.
  • st modulates cell cycle progression, correlating with its apoptotic effects.

Conclusions:

  • Simian virus 40 small t antigen (st) can induce p53-independent apoptosis in certain cell types.
  • The interaction of st with PP2A, particularly in vivo, is critical for its apoptotic function.
  • st's role is context-dependent, capable of promoting proliferation or inducing cell death based on cellular environment and specific viral protein interactions.

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