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A selection system for human apoptosis inhibitors using yeast.

W Greenhalf1, J Lee, B Chaudhuri

  • 1Oncology Research, Novartis Pharma AG, Basel, Switzerland. greenhaf@liverpool.ac.uk

Yeast (Chichester, England)
|October 6, 1999
PubMed
Summary

Researchers identified novel human genes, Bax antagonists selected in Saccharomyces (BASS), that protect cells from apoptosis. BASS proteins overcome toxicity in yeast and safeguard mammalian cells from programmed cell death.

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Apoptosis is a crucial cellular process regulated by the Bcl-2 gene family.
  • Bcl-2 family members either promote or inhibit apoptosis.
  • Bax-alpha (Bax), a pro-apoptotic protein, induces growth arrest and cell death in yeast.

Purpose of the Study:

  • To develop a system for isolating human genes that counteract Bax-induced toxicity in yeast.
  • To identify and characterize novel proteins that regulate apoptosis.

Main Methods:

  • Utilized yeast Saccharomyces cerevisiae as a model system to screen for human genes.
  • Expressed Bax-alpha in yeast to induce sensitivity.
  • Screened for human genes that confer resistance to Bax-induced toxicity.

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Main Results:

  • Identified two novel human genes, named Bax antagonists selected in Saccharomyces (BASS).
  • BASS proteins successfully overcame Bax-induced toxicity and growth arrest in yeast.
  • BASS proteins demonstrated protective effects against apoptosis in mammalian cells induced by staurosporine or Bax overexpression.
  • BASS2 was found to be more potent than BASS1.

Conclusions:

  • The yeast system is effective for isolating apoptosis-regulating genes.
  • BASS proteins represent a new class of apoptosis inhibitors.
  • BASS proteins have potential therapeutic applications in preventing mammalian cell death.