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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Mechanisms and Functions of Cell Death
TL;DR: Cell Death During the Metamorphosis of Moths, Cells That Develop Improperly, and Mechanisms That Kill Cells.
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WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis
Wafik S. El-Deiry,Harper Jw,O'Connor Pm,O'Connor Pm,Victor E. Velculescu,Christine E. Canman,Christine E. Canman,Jackman J,Jennifer A. Pietenpol,Marilee Burrell,David E. Hill,Yisong Wang +11 more
TL;DR: The results support the idea that WAF1/CIP1 is a critical downstream effector in the p53-specific pathway of growth control in mammalian cells.
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Specific Proteolytic Cleavage of Poly(ADP-ribose) Polymerase: An Early Marker of Chemotherapy-induced Apoptosis
TL;DR: The results suggest that proteolytic cleavage of pADPRp, in addition to being an early marker of chemotherapy-induced apoptosis, might reflect more widespread proteolysis that is a critical biochemical event early during the process of physiological cell death.
Journal ArticleDOI
Movement of Bax from the Cytosol to Mitochondria during Apoptosis
TL;DR: In cells undergoing apoptosis, an early, dramatic change occurs in the intracellular localization of Bax, and this redistribution of soluble Bax to organelle-bound GFP–Bax appears important for Bx to promote cell death.
Journal ArticleDOI
Apoptosis in cancer
Scott W. Lowe,Athena W. Lin +1 more
TL;DR: An intense research effort is uncovering the underlying mechanisms of apoptosis such that, in the next decade, one envisions that this information will produce new strategies to exploit apoptosis for therapeutic benefit.
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.
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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.
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.