The protein bcl-2 alpha does not require membrane attachment, but two conserved domains to suppress apoptosis
Details
Serval ID
serval:BIB_44EC5BE07004
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The protein bcl-2 alpha does not require membrane attachment, but two conserved domains to suppress apoptosis
Journal
Journal of Cell Biology
ISSN
0021-9525 (Print)
Publication state
Published
Issued date
08/1994
Volume
126
Number
4
Pages
1059-68
Notes
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Aug
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Aug
Abstract
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.
Keywords
Amino Acid Sequence
Animals
Animals, Newborn
*Apoptosis/drug effects
Base Sequence
Cell Survival
Cells, Cultured
Cloning, Molecular
Conserved Sequence
DNA Primers
Humans
L Cells (Cell Line)
Mice
Molecular Sequence Data
*Mutagenesis, Site-Directed
Neurons/*cytology/drug effects/*metabolism
Protein Biosynthesis
Protein-Tyrosine Kinases/metabolism
Proto-Oncogene Proteins/biosynthesis/*metabolism
Proto-Oncogene Proteins c-bcl-2
Rats
Recombinant Proteins/biosynthesis/metabolism
Sequence Deletion
Sequence Homology, Amino Acid
Superior Cervical Ganglion/cytology/*metabolism
Transcription, Genetic
Tumor Necrosis Factor-alpha/pharmacology
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 16:18
Last modification date
20/08/2019 14:49