http://www.cnr.it/ontology/cnr/individuo/prodotto/ID176790
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)
- Type
- 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
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
- Ildikò Szabò; Matthias Soddemann; Luigi Leanza; Mario Zoratti; Erich Gulbins (literal)
- Pagina inizio
- Pagina fine
- 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
- Rivista
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#pagineTotali
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
- 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)
- Prodotto di
- Autore CNR
- Insieme di parole chiave
Incoming links:
- Autore CNR di
- Prodotto
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi
- Insieme di parole chiave di