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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Proliferation and apoptosis in proliferative lesions of the colon and rectum.
TL;DR: The findings indicate that in the progression from adenoma to carcinoma both increased proliferation and decreased apoptosis occur, paralleled by an increased expression of p53 and an increased and predominantly cytoplasmic expression of c-myc, but a decreased expression of bcl-2.
Journal ArticleDOI
Review article: molecular, pathological and therapeutic features of human enteric neuropathies
G. Di Nardo,Corrado Blandizzi,Umberto Volta,R Colucci,Vincenzo Stanghellini,Giovanni Barbara,M. Del Tacca,Marcello Tonini,Roberto Corinaldesi,R. De Giorgio +9 more
TL;DR: This work has shown that directly manipulating enteric neuronal circuitries regulating gastrointestinal motility results in down-regulation in mice with autism and Down’s syndrome, and this work aims to clarify the mechanisms behind this phenomenon.
Journal ArticleDOI
Melatonin antagonizes the intrinsic pathway of apoptosis via mitochondrial targeting of Bcl-2.
Flavia Radogna,Silvia Cristofanon,Laura Paternoster,Laura Paternoster,Maria D'alessio,Milena De Nicola,Claudia Cerella,Mario Dicato,Marc Diederich,Lina Ghibelli +9 more
TL;DR: It is shown that melatonin interferes with the intrinsic pathway of apoptosis at the mitochondrial level, providing a mechanism that may explain how melatonin through interaction with the MT1/MT2 receptors, elicits a pathway that interfered with the Bcl‐2 family, thus modulating the cell life/death balance.
Journal ArticleDOI
Recent advances on neuronal caspases in development and neurodegeneration.
Neville Marks,Martin J. Berg +1 more
TL;DR: This overview emphasizes recent advances in neuronal caspases and their role in cell death, with emphasis on cytochrome c as pivotal in mediating conversion of procaspase-9 as a major initiator for apoptosis.
Journal ArticleDOI
The prevalence of BCL-2 immunoreactivity in breast carcinomas and its clinicopathological correlates, with particular reference to oestrogen receptor status
Claudio Doglioni,A. P. Dei Tos,Licia Laurino,Concetta Chiarelli,Mattia Barbareschi,Giuseppe Viale +5 more
TL;DR: It is concluded that bcl-2 expression in breast cancers is related to the oestrogen-dependent transcription pathway and therefore favouring a prolonged survival of normal and neoplastic cells.
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.