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rdf:type |
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lifeskim:mentions |
umls-concept:C0013935,
umls-concept:C0016030,
umls-concept:C0017262,
umls-concept:C0024337,
umls-concept:C0025914,
umls-concept:C0026809,
umls-concept:C0026882,
umls-concept:C0162638,
umls-concept:C0205314,
umls-concept:C0233820,
umls-concept:C0392747,
umls-concept:C0441712,
umls-concept:C0542341,
umls-concept:C0679622,
umls-concept:C1171362,
umls-concept:C1332397,
umls-concept:C1515670,
umls-concept:C1521991,
umls-concept:C1709915
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pubmed:issue |
3
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pubmed:dateCreated |
2011-2-14
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pubmed:abstractText |
Members of the Bcl-2 family play key roles as proapoptotic (e.g., Bax) and antiapoptotic (e.g., Bcl-x(L)) regulators of programmed cell death. We previously identified the mitochondrial potassium channel Kv1.3 as a novel target of Bax. Incubating Kv1.3-positive isolated mitochondria with Bax triggered apoptotic events, whereas Kv1.3-deficient mitochondria were resistant to this stimulus. Mutation of Bax at lysine 128 (BaxK128E) abrogated its effects on Kv1.3 and the induction of apoptotic changes in mitochondria. These data indicate a toxin-like action of Bax on Kv1.3 to trigger at least some of the mitochondrial changes typical for apoptosis. To gain insight into the mechanism of Bax-Kv1.3 interaction, we mutated Glu158 of Bcl-x(L) (corresponding to K128 in Bax) to lysine. This substitution turned Bcl-x(L) proapoptotic. Transfection of double knockout (Bax(-/-)/Bak(-/-)) mouse embryonic fibroblasts (DKO MEFs) with either wild-type Bax, BaxK128E, or Bcl-x(L)E158K showed that apoptosis induced by various stimuli was defective in DKO MEFs and BaxK128E-transfected cells, but was recovered upon transfection with Bcl-xLE158K or wild-type Bax. Both wild-type Bax and BaxK128E can form similar ion-conducting pores upon incorporation into planar lipid bilayers. Our results point to a physiologically relevant interaction of Bax with Kv1.3 and further indicate a crucial role of a distinct lysine in determining the proapoptotic character of Bcl2-family proteins.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1476-5403
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
18
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
427-38
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pubmed:meshHeading |
pubmed-meshheading:20885444-Amino Acid Sequence,
pubmed-meshheading:20885444-Animals,
pubmed-meshheading:20885444-Apoptosis,
pubmed-meshheading:20885444-Cytochromes c,
pubmed-meshheading:20885444-Embryo, Mammalian,
pubmed-meshheading:20885444-Fibroblasts,
pubmed-meshheading:20885444-Humans,
pubmed-meshheading:20885444-Ion Channel Gating,
pubmed-meshheading:20885444-Jurkat Cells,
pubmed-meshheading:20885444-Kv1.3 Potassium Channel,
pubmed-meshheading:20885444-Lipid Bilayers,
pubmed-meshheading:20885444-Lysine,
pubmed-meshheading:20885444-Membrane Potential, Mitochondrial,
pubmed-meshheading:20885444-Mice,
pubmed-meshheading:20885444-Molecular Sequence Data,
pubmed-meshheading:20885444-Mutant Proteins,
pubmed-meshheading:20885444-Point Mutation,
pubmed-meshheading:20885444-Protein Structure, Quaternary,
pubmed-meshheading:20885444-Sequence Homology, Amino Acid,
pubmed-meshheading:20885444-bcl-2 Homologous Antagonist-Killer Protein,
pubmed-meshheading:20885444-bcl-2-Associated X Protein,
pubmed-meshheading:20885444-bcl-X Protein
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pubmed:year |
2011
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pubmed:articleTitle |
Single-point mutations of a lysine residue change function of Bax and Bcl-xL expressed in Bax- and Bak-less mouse embryonic fibroblasts: novel insights into the molecular mechanisms of Bax-induced apoptosis.
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pubmed:affiliation |
Department of Biology, University of Padova, Padova, Italy. ildi@civ.bio.unipd.it
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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