title: BH3-only proteins: a 20-year stock-take.
abstract: BH3-only proteins are the sentinels of cellular stress, and their activation commits cells to apoptosis. Since the discovery of the first BH3-only protein BAD almost 20 years ago, at least seven more BH3-only proteins have been identified in mammals. They are regulated by a variety of environmental stimuli or by developmental cues, and play a crucial role in cellular homeostasis. Some are considered to be tumor suppressors, and also play a significant role in other pathologies. Their non-apoptotic functions are controversial, but there is broad consensus emerging regarding their role in apoptosis, which may help in designing better therapeutic agents for treating a variety of human diseases.
authors.affiliation: Department of Biochemistry, La Trobe Institute of Molecular Science, La Trobe University, Melbourne, Australia.
authors.forename: Marcel
authors.initials: M
authors.lastname: Doerflinger
authors.forename: Jason A
authors.initials: JA
authors.lastname: Glab
authors.forename: Hamsa
authors.initials: H
authors.lastname: Puthalakath
mesh_terms: D000818:Animals; D017209:Apoptosis; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004249:DNA Damage; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D017434:Protein Structure, Tertiary; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: C494772:BAK1 protein, human; C494826:BAX protein, human; D051023:BH3 Interacting Domain Death Agonist Protein; D029742:Caenorhabditis elegans Proteins; C087233:Ced-9 protein, C elegans; C112486:EGL-1 protein, C elegans; D008565:Membrane Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012097:Repressor Proteins; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; C422043:ced-1 protein, C elegans; D020169:Caspases; C089223:ced-3 protein, C elegans
keywords: BH3-only proteins; Bak; Bax; Bcl-2 family; activation; activationapoptosis; disease; mimetics; oligomerization; therapeutics