Accession Number : ADA332479

Title :   Training in Support of Research Project Entitled Genetic Regulation of the Bcl-2/Bax Cell Death Pathway.

Descriptive Note : Annual rept. 1 Jul 96-30 Jun 97

Corporate Author : BURNHAM INST LA JOLLA CA

Personal Author(s) : Xu, Qunli

PDF Url : ADA332479

Report Date : JUL 1997

Pagination or Media Count : 26

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.

Descriptors :   *DEOXYRIBONUCLEIC ACIDS, *DEATH, *CELLS(BIOLOGY), *GENETICS, MAMMALS, HUMANS, PROTEINS, COMPUTER PROGRAMMING, CROSSLINKING(CHEMISTRY), MEMBRANES, YEASTS, GENES, IN VIVO ANALYSIS, AMINO ACIDS, BREAST CANCER.

Subject Categories : Genetic Engineering and Molecular Biology
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE