Bcl2-L-10, a novel anti-apoptotic member of the Bcl-2 family, blocks apoptosis in the mitochondria death pathway but not in the death receptor pathway.
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.
Zhang
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H
University Women's Hospital Basel, Schanzenstrasse 46, CH-4031 Basel, Switzerland. hzhang@uhbs.ch
Holzgreve
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W
De Geyter
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C
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics / Q000502:physiology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D003574:Cytochrome c Group / Q000378:metabolism; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D005260:Female; D015870:Gene Expression; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D007425:Intracellular Membranes / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D008928:Mitochondria / Q000502:physiology*; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014018:Tissue Distribution; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; C117144:BCL2-like 10 protein; D003574:Cytochrome c Group; D018076:DNA, Complementary; D007377:Interleukin-3; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases