Abstract
By GenBank database searches and PCR, we have identified a novel human Bcl2-like gene, Bcl2-L-10, which contains conserved BH4, BH1 and BH2 domains but lacks BH3 domain. The Bcl2-L-10 gene has been assigned to chromosome 15q21.2. Transfection experiments demonstrated that Bcl2-L-10 can block apoptosis induced by interleukin-3 withdrawal and Bax expression, by prevention of cytochrome C release, caspase-3 activation and mitochondrial membrane potential collapse. Bcl2-L-10 cannot block TNFalpha-induced apoptosis. Furthermore, both the BH4 domain and the transmembrane domain of Bcl2-L-10 are necessary for its suppressive action on cell death. Our results demonstrated that Bcl2-L-10 is a newly detected anti-apoptotic member of the Bcl-2 family and that it blocks apoptosis in the mitochondrial death pathway but not in the death receptor pathway.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Apoptosis / drug effects
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Apoptosis / genetics
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Apoptosis / physiology*
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Base Sequence
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Binding Sites / genetics
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Binding Sites / physiology
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Caspase 3
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Caspases / metabolism
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Cell Line
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Cell Survival / genetics
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Cell Survival / physiology
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Chromosome Mapping
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Chromosomes, Human, Pair 15 / genetics
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Cytochrome c Group / metabolism
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DNA, Complementary / chemistry
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DNA, Complementary / genetics
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Female
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Gene Expression
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Genetic Vectors / genetics
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Humans
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Interleukin-3 / pharmacology
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Intracellular Membranes / physiology
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Male
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Membrane Potentials / physiology
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Membrane Proteins / genetics
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Membrane Proteins / physiology
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Mitochondria / physiology*
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Molecular Sequence Data
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / physiology
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / physiology*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Receptors, Tumor Necrosis Factor / physiology*
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Sequence Alignment
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Sequence Analysis, DNA
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Sequence Homology, Amino Acid
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Signal Transduction
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Tissue Distribution
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Tumor Necrosis Factor-alpha / pharmacology
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bcl-2-Associated X Protein
Substances
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BAX protein, human
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BCL2-like 10 protein
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Cytochrome c Group
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DNA, Complementary
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Interleukin-3
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Membrane Proteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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RNA, Messenger
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Receptors, Tumor Necrosis Factor
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Tumor Necrosis Factor-alpha
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bcl-2-Associated X Protein
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CASP3 protein, human
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Caspase 3
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Caspases