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Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death
D Hockenbery1, G Nuñez, C Milliman
1Department of Medicine, Howard Hughes Medical Institute, Washington University School of Medicine, St Louis, Missouri 63110.
Nature
|November 22, 1990
Summary
The bcl-2 gene fusion, found in follicular lymphoma, leads to prolonged cell survival by preventing programmed cell death. This proto-oncogene is located in mitochondria and impacts cell death independently of cell division.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- Follicular B-cell lymphoma is characterized by the t(14;18) chromosomal translocation.
- This translocation deregulates the bcl-2 gene, leading to elevated bcl-2 RNA and protein levels.
Purpose of the Study:
- To investigate the function and localization of the Bcl-2 protein.
- To understand the role of Bcl-2 in cell survival and apoptosis.
Main Methods:
- Utilized transgenic mice models with a bcl-2 immunoglobulin minigene.
- Employed immunolocalization studies to determine Bcl-2 protein location.
- Assessed the impact of Bcl-2 overexpression on pro-B-lymphocyte cell lines.
Main Results:
- Transgenic mice showed a polyclonal expansion of B cells with prolonged survival but no increased cell cycling.
- Deregulated bcl-2 extended the survival of hematopoietic cell lines after growth factor deprivation.
- Bcl-2 was identified as an integral inner mitochondrial membrane protein (25 kDa).
- Overexpression of Bcl-2 inhibited apoptosis in a pro-B-lymphocyte cell line.
Conclusions:
- Bcl-2 is a unique proto-oncogene localized to mitochondria.
- Bcl-2 interferes with programmed cell death (apoptosis) without promoting cell division.
- The findings provide insights into the mechanism of lymphoma development and potential therapeutic targets.