Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death.
The t(14; 18) chromosomal translocation of human follicular B-cell lymphoma juxtaposes the bcl-2 gene with the immunoglobulin heavy chain locus. The bcl-2 immunoglobulin fusion gene is markedly deregulated resulting in inappropriately elevated levels of bcl-2 RNA and protein. 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. Moreover, deregulated bcl-2 extends the survival of certain haematopoietic cell lines following growth-factor deprivation. 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.
Hockenbery
D
D
Department of Medicine, Howard Hughes Medical Institute, Washington University School of Medicine, St Louis, Missouri 63110.
Nuñez
G
G
Milliman
C
C
Schreiber
R D
RD
Korsmeyer
S J
SJ
D000818:Animals; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival; D002883:Chromosomes, Human, Pair 14; D002887:Chromosomes, Human, Pair 18; D003062:Codon / Q000235:genetics; D006801:Humans; D008223:Lymphoma / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D008928:Mitochondria / Q000378:metabolism*; D008969:Molecular Sequence Data; D009857:Oncogenes; D016366:Open Reading Frames; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D014178:Translocation, Genetic
D000911:Antibodies, Monoclonal; D003062:Codon; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2