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

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

doi:10.1038/348334a0

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

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

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543 Scopus citations

Abstract

THE t(14; 18) chromosomal translocation of human follicular B-cell lymphoma juxtaposes the bcl-2 gene with the immunoglobulin heavy chain locus^1-3. The bcl-2 immunoglobulin fusion gene is markedly deregulated resulting in inappropriately elevated levels of bcl-2 RNA and protein^4-7. 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 cycling^8,9. Moreover, deregulated bcl-2 extends the survival of certain haematopoietic cell lines following growth-factor deprivation^10,11. 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.

Original language	English
Pages (from-to)	334-336
Number of pages	3
Journal	Nature
Volume	348
Issue number	6299
DOIs	https://doi.org/10.1038/348334a0
State	Published - 1990

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title = "Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death",

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.",

author = "David Hockenbery and Gabriel Nu{\~n}ez and Curt Milliman and Schreiber, {Robert D.} and Korsmeyer, {Stanley J.}",

year = "1990",

doi = "10.1038/348334a0",

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volume = "348",

pages = "334--336",

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T1 - Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death

AU - Hockenbery, David

AU - Nuñez, Gabriel

AU - Milliman, Curt

AU - Schreiber, Robert D.

AU - Korsmeyer, Stanley J.

PY - 1990

Y1 - 1990

N2 - 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.

AB - 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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ER -

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

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