Abstract
Autophagy, a cellular degradation system, promotes both cell death and survival. The interaction between Bcl-2 family proteins and Beclin 1, a Bcl-2 interacting protein that promotes autophagy, can mediate crosstalk between autophagy and apoptosis. We investigated the interaction between anti-and pro-apoptotic Bcl-2 proteins with Beclin 1. Our results show that Beclin 1 directly interacts with Bcl-2, Bcl-x(L), Bcl-w and to a lesser extent with Mcl-1. Beclin 1 does not bind the pro-apoptotic Bcl-2 proteins. The interaction between Beclin 1 and the anti-apoptotic protein Bcl-x(L) was inhibited by BH3-only proteins, but not by multi-domain proteins. Sequence alignment and structural modeling suggest that Beclin 1 contains a putative BH3-like domain which may interact with the hydrophobic grove of Bcl-x(L). Mutation of the Beclin 1 amino acids predicted to mediate this interaction inhibited the association of Beclin 1 with Bcl-x(L). Our results suggest that BH3 only proapoptotic Bcl-2 proteins may modulate the interactions between Bcl-x(L) and Beclin 1.
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
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Apoptosis Regulatory Proteins / chemistry
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Apoptosis Regulatory Proteins / genetics
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Apoptosis Regulatory Proteins / metabolism*
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Autophagy
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BH3 Interacting Domain Death Agonist Protein / metabolism
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Beclin-1
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COS Cells
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Cell Line
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Chlorocebus aethiops
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Glutathione Transferase / metabolism
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Humans
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Kidney / cytology
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Membrane Proteins / chemistry
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Models, Molecular
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Molecular Sequence Data
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Myeloid Cell Leukemia Sequence 1 Protein
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Neoplasm Proteins / metabolism*
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Plasmids
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Protein Structure, Tertiary / genetics
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Proto-Oncogene Proteins c-bcl-2 / metabolism*
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / metabolism
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Sequence Homology, Amino Acid
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Transfection
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bcl-2-Associated X Protein / metabolism*
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bcl-X Protein / chemistry
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bcl-X Protein / metabolism*
Substances
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Apoptosis Regulatory Proteins
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BCL2L2 protein, human
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BECN1 protein, human
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BH3 Interacting Domain Death Agonist Protein
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Beclin-1
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Membrane Proteins
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Myeloid Cell Leukemia Sequence 1 Protein
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Neoplasm Proteins
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Proto-Oncogene Proteins c-bcl-2
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Recombinant Fusion Proteins
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bcl-2-Associated X Protein
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bcl-X Protein
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Glutathione Transferase