title: BAR: An apoptosis regulator at the intersection of caspases and Bcl-2 family proteins.
abstract: Two major pathways for induction of apoptosis have been identified-intrinsic and extrinsic. The extrinsic pathway is represented by tumor necrosis factor family receptors, which utilize protein interaction modules known as death domains and death effector domains (DEDs) to assemble receptor signaling complexes that recruit and activate certain caspase-family cell death proteases, namely procaspases-8 and -10. The intrinsic pathway for apoptosis involves the participation of mitochondria, which release caspase-activating proteins. Bcl-2 family proteins govern this mitochondria-dependent apoptosis pathway, with proteins such as Bax functioning as inducers and proteins such as Bcl-2 and Bcl-X(L) serving as suppressors of cell death. An apoptosis regulator, BAR, was identified by using a yeast-based screen for inhibitors of Bax-induced cell death. The BAR protein contains a SAM domain, which is required for its interactions with Bcl-2 and Bcl-X(L) and for suppression of Bax-induced cell death in both mammalian cells and yeast. In addition, BAR contains a DED-like domain responsible for its interaction with DED-containing procaspases and suppression of Fas-induced apoptosis. Furthermore, BAR can bridge procaspase-8 and Bcl-2 into a protein complex. The BAR protein is anchored in intracellular membranes where Bcl-2 resides. BAR therefore may represent a scaffold protein capable of bridging two major apoptosis pathways.
authors.affiliation: Program on Apoptosis and Cell Death Regulation, The Burnham Institute, La Jolla, CA 92037, USA.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: Q
authors.initials: Q
authors.lastname: Xu
authors.forename: S
authors.initials: S
authors.lastname: Krajewski
authors.forename: M
authors.initials: M
authors.lastname: Krajewska
authors.forename: Z
authors.initials: Z
authors.lastname: Xie
authors.forename: S
authors.initials: S
authors.lastname: Fuess
authors.forename: S
authors.initials: S
authors.lastname: Kitada
authors.forename: K
authors.initials: K
authors.lastname: Pawlowski
authors.forename: A
authors.initials: A
authors.lastname: Godzik
authors.forename: J C
authors.initials: JC
authors.lastname: Reed
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000737:chemistry / Q000502:physiology*; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D004792:Enzyme Precursors / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000737:chemistry / Q000502:physiology*; D008969:Molecular Sequence Data; D010957:Plasmids; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D020798:Two-Hybrid System Techniques; D051028:bcl-2-Associated X Protein; D019014:fas Receptor / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C494826:BAX protein, human; C406792:BFAR protein, human; D002352:Carrier Proteins; D018076:DNA, Complementary; D004792:Enzyme Precursors; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases