A selection system for human apoptosis inhibitors using yeast

Apoptosis is a regulated series of events which leads to the death and elim ination of mammalian cells during development or in disease control. It is regulated in part by members of the Bcl-2 family of genes. Some of these st imulate cell death, while others prevent it. Expression of one of these dea th inducers, Bar-a (Bar), in the yeast Saccharomyces cerevisiae induces gro wth arrest and subsequently can cause cell death. Proteins of the Bcl-2 fam ily that are known to inhibit apoptosis in mammalian cells overcome Bar-ind uced growth arrest in yeast. We describe here a system for isolation of hum an genes that are able to overcome Bar sensitivity in yeast. Two novel prot eins, identified with this system, have been named 'Bar antagonists selecte d in saccharomyces (BASS). These proteins not only overcome toxicity of Bar in yeast but also protect mammalian cells from apoptosis that is induced b y staurosporine or Bar overexpression. We find that BASS2 is the more effec tive of the two genes. Copyright (C) 1999 John Wiley & Sons, Ltd.