title: Evolutionarily conserved cytoprotection provided by Bax Inhibitor-1 homologs from animals, plants, and yeast.
abstract: Programmed cell death (PCD) plays important roles in the development and physiology of both animals and plants, but it is unclear whether similar mechanisms are employed. Bax Inhibitor-1 (BI-1) is an intracellular multi-membrane-spanning protein and cell death inhibitor, originally identified by a function-based screen for mammalian cDNAs capable of suppressing cell death in yeast engineered to ectopically express the pro-apoptotic protein Bax. Using this yeast assay, we screened expression libraries for cDNAs from the plant, Lycopersicon esculentum (tomato), and the invertebrate animal Drosophila melanogaster (fruit fly), identifying close homologs of BI-1 as Bax-suppressors. We studied the fly and tomato homologs of BI-1, as well as BI-1 homologs identified in Arabidopsis thaliana, Oryza sativa (rice), and Saccharomyces cerevisiae (budding yeast). All eukaryotic homologs of BI-1 blocked Bax-induced cell death when expressed in yeast. Eukaryotic BI-1 homologs also partially rescued yeast from cell death induced by oxidative stress (H(2)O(2)) and heat shock. Deletion of a C-terminal domain from BI-1 homologs abrogated their cytoprotective function in yeast, demonstrating conserved structure-function relations among these proteins. Expression of tomato BI-1 by agroinfiltration of intact plant leaves provided protection from damage induced by heat-shock and cold-shock stress. Altogether, these findings indicate that BI-1 homologs exist in multiple eukaryotic species, providing cytoprotection against diverse stimuli, thus implying that BI-1 regulates evolutionary conserved mechanisms of stress resistance that are germane to both plants and animals.
authors.affiliation: The Burnham Institute, La Jolla, CA 92037, USA.
authors.forename: Han-Jung
authors.initials: HJ
authors.lastname: Chae
authors.forename: Ning
authors.initials: N
authors.lastname: Ke
authors.forename: Hyung-Ryong
authors.initials: HR
authors.lastname: Kim
authors.forename: Shaorong
authors.initials: S
authors.lastname: Chen
authors.forename: Adam
authors.initials: A
authors.lastname: Godzik
authors.forename: Martin
authors.initials: M
authors.lastname: Dickman
authors.forename: John C
authors.initials: JC
authors.lastname: Reed
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D051017:Apoptosis Regulatory Proteins; D029681:Arabidopsis Proteins; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D017124:Conserved Sequence / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics / Q000302:isolation & purification; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development; D019143:Evolution, Molecular; D015723:Gene Library; D005816:Genetic Complementation Test; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015151:Immunoblotting; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D063245:Plant Development; D010944:Plants / Q000235:genetics*; D030821:Plants, Genetically Modified; D011506:Proteins; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D013696:Temperature
chemical_list: C491862:ATBI-1 protein, Arabidopsis; D051017:Apoptosis Regulatory Proteins; D029681:Arabidopsis Proteins; D018076:DNA, Complementary; D008565:Membrane Proteins; D011506:Proteins; C484209:TMBIM6 protein, human; D006861:Hydrogen Peroxide