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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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Journal ArticleDOI

Mitochondrial apoptotic pathways.

TL;DR: A significant difference has been shown between mammaliancell apoptosis and non-mammalian cell apoptosis: mitochondria are implicated only in the former, and nowadays, execution of apoptosis is better known than its regulation.
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All along the watchtower: on the regulation of apoptosis regulators

TL;DR: How the regulation of these apoptosis regulators may control the ultimate fate of the cell is discussed.
Journal ArticleDOI

Rapid turnover of mcl-1 couples translation to cell survival and apoptosis.

TL;DR: Investigation of the hypothesis that selective degradation of anti-apoptotic regulatory protein(s) is responsible for apoptosis resulting from translation inhibition finds that Mcl-1 may serve as a convergence point for signals that affect global translation, coupling translation to cell survival and the apoptotic machinery.
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Correction: Corrigendum: Combinatorial nanocarrier based drug delivery approach for amalgamation of anti-tumor agents in breast cancer cells: an improved nanomedicine strategy

TL;DR: This research presents a novel probabilistic procedure called “spot-spot analysis” that allows for direct measurement of the response of the immune system to chemotherapy-like substances.
Journal ArticleDOI

Positive and negative selection of T cells in T-cell receptor transgenic mice expressing a bcl-2 transgene.

TL;DR: Although bcl-2 expression hampers the deletion of immature self-reactive cells in the thymus, self-tolerance is maintained, and TCR-MHC interaction may induce positive selection through two signals, one which saves cells from death by increasing BCl-2 synthesis and another which promotes maturation.
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.
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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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