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

Hum Mol Genet. 2001 Oct 1;10(21):2329-39. doi: 10.1093/hmg/10.21.2329.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Apoptosis / physiology*
  • Base Sequence
  • Binding Sites / genetics
  • Binding Sites / physiology
  • Caspase 3
  • Caspases / metabolism
  • Cell Line
  • Cell Survival / genetics
  • Cell Survival / physiology
  • Chromosome Mapping
  • Chromosomes, Human, Pair 15 / genetics
  • Cytochrome c Group / metabolism
  • DNA, Complementary / chemistry
  • DNA, Complementary / genetics
  • Female
  • Gene Expression
  • Genetic Vectors / genetics
  • Humans
  • Interleukin-3 / pharmacology
  • Intracellular Membranes / physiology
  • Male
  • Membrane Potentials / physiology
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology
  • Mitochondria / physiology*
  • Molecular Sequence Data
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / physiology
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / physiology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Tumor Necrosis Factor / physiology*
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Tissue Distribution
  • Tumor Necrosis Factor-alpha / pharmacology
  • bcl-2-Associated X Protein

Substances

  • BAX protein, human
  • BCL2-like 10 protein
  • Cytochrome c Group
  • DNA, Complementary
  • Interleukin-3
  • Membrane Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • bcl-2-Associated X Protein
  • CASP3 protein, human
  • Caspase 3
  • Caspases

Associated data

  • GENBANK/AF285092