Apoptosis initiated when BH3 ligands engage multiple Bcl-2 homologs, not Bax or Bak.
A central issue in the regulation of apoptosis by the Bcl-2 family is whether its BH3-only members initiate apoptosis by directly binding to the essential cell-death mediators Bax and Bak, or whether they can act indirectly, by engaging their pro-survival Bcl-2-like relatives. Contrary to the direct-activation model, we show that ... Bax and Bak can mediate apoptosis without discernable association with the putative BH3-only activators (Bim, Bid, and Puma), even in cells with no Bim or Bid and reduced Puma. Our results indicate that BH3-only proteins induce apoptosis at least primarily by engaging the multiple pro-survival relatives guarding Bax and Bak.
Mesh Terms:
Animals, Apoptosis, Apoptosis Regulatory Proteins, BH3 Interacting Domain Death Agonist Protein, Cell Line, Cells, Cultured, Humans, Ligands, Membrane Proteins, Mice, Mice, Knockout, Models, Biological, Mutation, Myeloid Cell Leukemia Sequence 1 Protein, Neoplasm Proteins, Protein Structure, Tertiary, Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-bcl-2, Tumor Suppressor Proteins, bcl-2 Homologous Antagonist-Killer Protein, bcl-2-Associated X Protein, bcl-Associated Death Protein, bcl-X Protein
Animals, Apoptosis, Apoptosis Regulatory Proteins, BH3 Interacting Domain Death Agonist Protein, Cell Line, Cells, Cultured, Humans, Ligands, Membrane Proteins, Mice, Mice, Knockout, Models, Biological, Mutation, Myeloid Cell Leukemia Sequence 1 Protein, Neoplasm Proteins, Protein Structure, Tertiary, Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-bcl-2, Tumor Suppressor Proteins, bcl-2 Homologous Antagonist-Killer Protein, bcl-2-Associated X Protein, bcl-Associated Death Protein, bcl-X Protein
Science
Date: Feb. 09, 2007
PubMed ID: 17289999
View in: Pubmed Google Scholar
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