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.read more
Citations
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Journal ArticleDOI
Programmed Cell Death and the Control of Cell Survival
TL;DR: The amount of normal cell death in mammalian development is still underestimated and the possibility that the death programme, like mitosis, is orchestrated by a cytosolic regulator that acts on multiple organelles in parallel is raised.
Journal ArticleDOI
Role of nitric oxide in mediation of macrophage cytotoxicity and apoptosis
TL;DR: This review will initially discusss the characteristics of macrophage tumor cytotoxicity and the potential mechanisms by which NO can induce apoptosis in tumor cells and the relevance of results obtained using animal cells to the biology of the human macrophages will be considered.
Book ChapterDOI
The Bcl-2 Protein Family
Liam O'Connor,Andreas Strasser +1 more
TL;DR: Apoptosis can be caused by a broad range of physiological stimuli or experimentally applied stress conditions, and it appears that cells from all tissue types and from all multi-cellular organisms studied thus far possess this evolutionarily conserved death programme.
Journal ArticleDOI
Resveratrol, a tumor-suppressive compound from grapes, induces apoptosis via a novel mitochondrial pathway controlled by Bcl-2.
Inge Tinhofer,David Bernhard,Monika Senfter,Gabriele Anether,Markus Loeffler,Guido Kroemer,Reinhard Kofler,Adam Csordas,Richard Greil +8 more
TL;DR: Inhibition of ∆Ψm breakdown and of ROS generation by N‐acetylcysteine, or by overexpression of Bcl‐2 protein, prevented apoptosis induction by resveratrol.
Journal ArticleDOI
Molecular determinants of retinal ganglion cell development, survival, and regeneration
TL;DR: The molecular determinants of RGC fate determination and the development of the retino-tectal projection are reviewed and perspectives towards neuroprotection and regeneration of adult lesioned RGCs that may be applicable to lesioned CNS neurons in vertebrates in a broader sense are developed.
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.
Journal ArticleDOI
Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation
Yoshihide Tsujimoto,Lawrence R. Finger,Jorge J. Yunis,Peter C. Nowell,Carlo M. Croce,Carlo M. Croce +5 more
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.
Timothy J. McDonnell,Natasha Deane,Frances M. Platt,Gabriel Núñez,Ulrich Jaeger,John P. McKearn,Stanley J. Korsmeyer +6 more
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.