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Journal ArticleDOI

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

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TLDR
It is demonstrated that Bcl-2 is an integral inner mitochondrial membrane protein of relative molecular mass 25,000 (25k) being localized to mitochondria and interfering with programmed cell death independent of promoting cell division.
Abstract
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.

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Citations
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Neuroprotective Action of Cycloheximide Involves Induction of Bcl-2 and Antioxidant Pathways

TL;DR: Evidence is provided that in embryonic rat hippocampal cell cultures, CHX protects neurons against oxidative insults by a mechanism involving induction of neuroprotective gene products including the antiapoptotic gene bcl-2 and antioxidant enzymes.
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Mitochondria-mediated cell injury. Symposium overview.

TL;DR: A review of chemical-induced cytotoxic responses that are manifested as interference with mitochondrial metabolism and bioenergetics, gene regulation, or signal transduction in the form of apoptosis and altered cell cycle control can be found in this article.
Journal ArticleDOI

Mitochondrial Retrograde Signaling: Triggers, Pathways, and Outcomes.

TL;DR: Mitochondria-to-nucleus retrograde signaling has been described in various organisms, albeit with differences in effector pathways, molecules, and outcomes, as discussed in this review.
Journal ArticleDOI

Activation-induced T-cell death is cell cycle dependent and regulated by cyclin B.

TL;DR: It is concluded that a persistent elevation of the level of cyclin B kinase is required for activation-induced programmed T-cell death.
Journal ArticleDOI

Susceptibility to drug-induced apoptosis correlates with differential modulation of Bad, Bcl-2 and Bcl-xL protein levels.

TL;DR: It is concluded that Bad up-regulation is an early indicator of a cellular response that will lead to cell death, but may be modulated by survival mechanisms, which cumulatively govern the ultimate susceptibility to apoptosis.
References
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Journal ArticleDOI

Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells.

TL;DR: Results argue that bcl-2 provided a distinct survival signal to the cell and may contribute to neoplasia by allowing a clone to persist until other oncogenes, such as c-myc, become activated.
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Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation

TL;DR: In this paper, a DNA probe was obtained from an acute B-cell leukemia cell line, which was specific for chromosome 18 and flanked the heavy chain joining region of the immunoglobulin heavy chain locus on chromosome 14.
Journal ArticleDOI

Chromatin cleavage in apoptosis: association with condensed chromatin morphology and dependence on macromolecular synthesis.

TL;DR: The data confirm that the condensed chromatin which characterizes apoptosis morphologically consists of endogenously digested chromatin fragments, and provide support for the view that at least some cells enter apoptosis by a process dependent upon macromolecular synthesis.
Journal ArticleDOI

Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t(14;18) translocation

TL;DR: The results suggest that t(14;18) translocations alter expression of the bcl-2 gene both by transcriptional activation and by abnormal posttranscriptional regulation of bCl-2 mRNA.
Journal ArticleDOI

bcl-2-immunoglobulin transgenic mice demonstrate extended B cell survival and follicular lymphoproliferation.

TL;DR: In this article, minigene constructs representing the bcl-2-Ig fusion gene found at this chromosomal breakpoint were placed into the germ line of mice to assess the effects of the t(14;18) interchromosomal translocation during development.
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