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. (Articolo in rivista)

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Label
  • 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. (Articolo in rivista) (literal)
Anno
  • 2011-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1038/cdd.2010.112 (literal)
Alternative label
  • Ildikò Szabò; Matthias Soddemann; Luigi Leanza; Mario Zoratti; Erich Gulbins (2011)
    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.
    in Cell death and differentiation
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Ildikò Szabò; Matthias Soddemann; Luigi Leanza; Mario Zoratti; Erich Gulbins (literal)
Pagina inizio
  • 427 (literal)
Pagina fine
  • 438 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#url
  • http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3132001/?tool=pubmed (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 18 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#pagineTotali
  • 12 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 3 (literal)
Note
  • PubMe (literal)
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Ildikò Szabò; Luigi Leanza: Dip. di Biologia, Università di Padova. Matthias Soddemann; Erich Gulbins: Dept. of Molecular Biology, University of Duisburg-Essen, Germany. Mario Zoratti: In - Padova e dip. Scienze Biomediche Sperimentali, Università di Padova. (literal)
Titolo
  • 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. (literal)
Abstract
  • 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. (literal)
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