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.
Keywords:
BH3-only proteins; Bak; Bax; Bcl-2 family; activation; activationapoptosis; disease; mimetics; oligomerization; therapeutics.
© 2015 FEBS.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Apoptosis*
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BH3 Interacting Domain Death Agonist Protein / metabolism
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Caenorhabditis elegans
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Caenorhabditis elegans Proteins / metabolism
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Caspases / metabolism
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Cell Membrane / metabolism
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DNA Damage
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Gene Expression Regulation
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Homeostasis
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Humans
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Membrane Proteins / metabolism
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Mitochondria / metabolism
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Neoplasms / drug therapy
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Neoplasms / metabolism
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Protein Structure, Tertiary
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Repressor Proteins / metabolism
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bcl-2 Homologous Antagonist-Killer Protein / metabolism*
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bcl-2-Associated X Protein / metabolism*
Substances
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BAK1 protein, human
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BAX protein, human
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BH3 Interacting Domain Death Agonist Protein
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Caenorhabditis elegans Proteins
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Ced-9 protein, C elegans
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EGL-1 protein, C elegans
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Membrane Proteins
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Proto-Oncogene Proteins c-bcl-2
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Repressor Proteins
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bcl-2 Homologous Antagonist-Killer Protein
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bcl-2-Associated X Protein
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ced-1 protein, C elegans
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Caspases
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ced-3 protein, C elegans