Functional similarity between adenovirus e1b 19k gene and bcl2 oncogene - mutant complementation and suppression of

B Tarodi1, T Subramanian, G Chinnadurai

  • 1ST LOUIS UNIV,MED CTR,INST MOLEC VIROL,3681 PK AVE,ST LOUIS,MO 63110.

Insights

Adenovirus E1B 19K protein mutants induce DNA fragmentation, similar to apoptosis. Human Bcl2 protein suppresses this DNA fragmentation, suggesting functional similarity between 19K and Bcl2 proteins.

Area of Science:

  • Molecular biology
  • Cell biology
  • Virology

Background:

  • Adenovirus mutants lacking the E1B 19-kilodalton (19K) protein induce DNA fragmentation, mimicking apoptosis.
  • Zinc ions inhibit DNA fragmentation in both 19K mutant-induced events and apoptosis.
  • The proto-oncogene Bcl2 is known to inhibit DNA fragmentation and programmed cell death.

Purpose of the Study:

  • To investigate the functional similarity between the adenovirus E1B 19K protein and the cellular proto-oncogene Bcl2.
  • To determine if Bcl2 can suppress DNA fragmentation induced by adenovirus E1B 19K mutants.

Main Methods:

  • Functional complementation analysis was performed.
  • Stable expression of human Bcl2 protein was utilized.
  • DNA fragmentation and cell death induced by DNA damaging agents (cisplatin, UV) were assessed.

Main Results:

  • Stable expression of human Bcl2 protein efficiently suppressed DNA fragmentation induced by the 19K mutant.
  • Both 19K and Bcl2 proteins demonstrated similar functions in suppressing DNA fragmentation.
  • Both proteins also suppressed DNA fragmentation and cell death induced by cisplatin and UV.

Conclusions:

  • The adenovirus E1B 19K protein is functionally similar to the Bcl2 protein.
  • Bcl2 can functionally complement the defect in the 19K mutant, suppressing DNA fragmentation and cell death.
  • These findings highlight a conserved mechanism for regulating DNA fragmentation and cell death.

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