The protein bcl-2 alpha does not require membrane attachment, but two conserved domains to suppress apoptosis.

Détails

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Accès restreint UNIL
Etat: Public
Version: Final published version
Licence: Non spécifiée
ID Serval
serval:BIB_44EC5BE07004
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
The protein bcl-2 alpha does not require membrane attachment, but two conserved domains to suppress apoptosis.
Périodique
The Journal of cell biology
Auteur⸱e⸱s
Borner C., Martinou I., Mattmann C., Irmler M., Schaerer E., Martinou J.C., Tschopp J.
ISSN
0021-9525 (Print)
ISSN-L
0021-9525
Statut éditorial
Publié
Date de publication
08/1994
Peer-reviewed
Oui
Volume
126
Numéro
4
Pages
1059-1068
Langue
anglais
Notes
Publication types: Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Bcl-2 is a mitochondrial- and perinuclear-associated protein that prolongs the lifespan of a variety of cell types by interfering with programmed cell death (apoptosis). Bcl-2 seems to function in an antioxidant pathway, and it is believed that membrane attachment mediated by a COOH-terminal hydrophobic tail is required for its full activity. To identify critical regions in bcl-2 alpha for subcellular localization, activity, and/or interaction with other proteins, we created, by site-directed mutagenesis, various deletion, truncation, and point mutations. We show here that membrane attachment is not required for the survival activity of bcl-2 alpha. A truncation mutant of bcl-2 alpha lacking the last 33 amino acids (T3.1) including the hydrophobic COOH terminus shows full activity in blocking apoptosis of nerve growth factor-deprived sympathetic neurons or TNF-alpha-treated L929 fibroblasts. Confocal microscopy reveals that the T3 mutant departs into the extremities of neurites in neurons and filopodias in fibroblasts. Consistently, T3 is predominantly detected in the soluble fraction by Western blotting, and is not inserted into microsomes after in vitro transcription/translation. We further provide evidence for motifs (S-N and S-II) at the NH2 and COOH terminus of bcl-2, which are crucial for its activity.
Mots-clé
Amino Acid Sequence, Animals, Animals, Newborn, Apoptosis/drug effects, Base Sequence, Cell Survival, Cells, Cultured, Cloning, Molecular, Conserved Sequence, DNA Primers, Humans, L Cells, Mice, Molecular Sequence Data, Mutagenesis, Site-Directed, Neurons/cytology, Neurons/drug effects, Neurons/metabolism, Protein Biosynthesis, Protein-Tyrosine Kinases/metabolism, Proto-Oncogene Proteins/biosynthesis, Proto-Oncogene Proteins/metabolism, Proto-Oncogene Proteins c-bcl-2, Rats, Recombinant Proteins/biosynthesis, Recombinant Proteins/metabolism, Sequence Deletion, Sequence Homology, Amino Acid, Superior Cervical Ganglion/cytology, Superior Cervical Ganglion/metabolism, Transcription, Genetic, Tumor Necrosis Factor-alpha/pharmacology
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 16:18
Dernière modification de la notice
09/08/2024 15:52
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