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Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death

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Abstract

THE t(14; 18) chromosomal translocation of human follicular B-cell lymphoma juxtaposes the bcl-2 gene with the immunoglobulin heavy chain locus1–3. The bcl-2 immunoglobulin fusion gene is markedly deregulated resulting in inappropriately elevated levels of bcl-2 RNA and protein4–7. Transgenic mice bearing a bcl-2 immunoglobulin minigene demonstrate a polyclonal expansion of resting yet responsive IgM–IgD B cells which display prolonged cell survival but no increase in cell cycling8,9. Moreover, deregulated bcl-2 extends the survival of certain haematopoietic cell lines following growth-factor deprivation10,11. By using immunolocalization studies we now demonstrate that Bcl-2 is an integral inner mitochondrial membrane protein of relative molecular mass 25,000 (25k). Overexpression of Bcl-2 blocks the apoptotic death of a pro-B-lymphocyte cell line. Thus, Bcl-2 is unique among proto-oncogenes, being localized to mitochondria and interfering with programmed cell death independent of promoting cell division.

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Authors and Affiliations

  1. Departments of Medicine, Molecular Microbiology, and Pathology, Howard Hughes Medical Institute, Washington University School of Medicine, St Louis, Missouri, 63110, USA

    David Hockenbery, Gabriel Nuñez, Curt Milliman, Robert D. Schreiber & Stanley J. Korsmeyer

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  1. David Hockenbery
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  2. Gabriel Nuñez
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  3. Curt Milliman
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  4. Robert D. Schreiber
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  5. Stanley J. Korsmeyer
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Hockenbery, D., Nuñez, G., Milliman, C. et al. Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature 348, 334–336 (1990). https://doi.org/10.1038/348334a0

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