Training in Support of Research Project Entitled Genetic Regulation of the Bcl-2/Bax Cell Death Pathway.
Abstract
Bcl-2 family proteins function in an evolutionarily conserved pathway regulating programmed cell death. In an effort to delineate this cell death pathway, we undertook a novel functional screening approach. The pro-apoptotic Bax protein not only promotes apoptosis in mammals, but can also induce cell death when expressed in yeast. Based on this observation, we screened a human cDNA library for genes whose products protect S. cerevisiae against Bax-killing. Two human proteins, designated Bax Inhibitors - 1 and -2 (BI- 1 and BI-2), were identified during the screen that inhibit the death-inducing activity of Bax both in yeast and in mammalian cell line models. The deduced amino acid sequence suggests that BI- 1 is likely an integral membrane protein with six potential transmembrane helices, and this was biochemically by showing that BI-l was predominantly located in the detergent-enriched phase during Triton X-l 14 phase separation. We found that BI- 1 is localized to intracellular membranes, similar to Bcl-2 and Bax. Moreover, BI-l is able to interact physically with Bcl-2 but not Bax, as demonstrated both by in vivo cross-linking and by co-immunoprecipitation assays. Therefore BI- 1 is a novel apoptosis regulator which functions in the Bcl-2/Bax pathway for programmed cell death.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1997
- Accession Number
- ADA332479
Entities
People
- Qunli Xu
Organizations
- Sanford Burnham Prebys Medical Discovery Institute