The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
Targeting of Bcl-2 to the mitochondrial outer membrane by a COOH-terminal signal anchor sequence.
Open accessAbstract
The protooncogene product Bcl-2 is an integral membrane protein that functions as a suppressor of programmed cell death. It contains a single predicted transmembrane segment located at its COOH terminus. Here, we show that the transmembrane domain of human Bcl-2 functions as a mitochondrial signal anchor sequence that targets and inserts the protein into the outer membrane in an Ncyto-C(in) orientation, leaving the bulk of the polypeptide facing the cytosol. Deletion of the COOH-terminal 22 amino acids of Bcl-2 abrogated protein targeting, whereas fusion of this domain to the COOH terminus of dihydrofolate reductase resulted in targeting and insertion of the hybrid protein into the outer membrane in a manner similar to that of Bcl-2. The sequence of the hydrophobic core of the Bcl-2 signal anchor is similar to the corresponding region of the NH2-terminal signal anchor of the mitochondrial outer membrane protein in yeast, Mas70p. A synthetic peptide comprising the Mas70p signal anchor sequence effectively competed for insertion of Bcl-2 into the outer membrane but had no effect on the comparatively low association that Bcl-2 makes with endoplasmic reticulum microsomes. Insertion of Bcl-2 into the mitochondrial outer membrane is mechanistically different than its association with microsomes.
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Cites
Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programed cell death
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Self-citationBCL2 protein is topographically restricted in tissues characterized by apoptotic cell death.
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Cited by
The mitochondrial permeability transition pore and its role in cell death
CROMPTON, M. (1999) · Biochemical Journal · doi:10.1042/bj3410233 · Cited by 2,432
The cell biology of mitochondrial membrane dynamics
Giacomello, M., Pyakurel, A., Glytsou, C., & Scorrano, L. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0210-7 · Cited by 1,550
Mitochondria and neuronal survival
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Self-citationMechanisms of Action of Bcl-2 Family Proteins
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Newly born peroxisomes are a hybrid of mitochondrial and ER-derived pre-peroxisomes
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Mediation of the antiapoptotic activity of Bcl-xL protein upon interaction with VDAC1 protein
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Regulation of neutrophil apoptosis
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Metadata
- Authors
- Nguyen, M., Millar, D. G., Yong, V. W., Korsmeyer, S. J., & Shore, G. C.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1993-12
- Volume
- 268
- Issue
- 34
- Pages
- 25265-25268
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2169404281
- Cited by
- 393
- References
- 4
- FWCI
- 6.99
- Type
- journal article
- Language
- en
- Open access
- hybrid
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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