Author
Yoshihide Tsujimoto
Other affiliations: Temple University, University of Pennsylvania
Bio: Yoshihide Tsujimoto is an academic researcher from Wistar Institute. The author has contributed to research in topics: Chromosomal translocation & Gene. The author has an hindex of 23, co-authored 27 publications receiving 7794 citations. Previous affiliations of Yoshihide Tsujimoto include Temple University & University of Pennsylvania.
Papers
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TL;DR: Chromosome 18-specific DNA probes for the areas flanking the breakpoints also detected RNA transcripts 6 kilobases in length in various cell types, and the gene coding for these transcript seems to be interrupted in most cases of follicular lymphomas carrying the t(14;18) chromosomal translocation.
Abstract: Recombinant DNA probes were cloned for the areas flanking the breakpoint on chromosome 18 in cells from a patient with acute lymphocytic leukemia of the B-cell type; cells of this line carry the t(14;18) chromosomal translocation. Two of the probes detected DNA rearrangements in approximately 60 percent of the cases of follicular lymphoma screened. In follicular lymphoma, most of the breakpoints in band q21 of chromosome 18 were clustered within a short stretch of DNA, approximately 2.1 kilobases in length. Chromosome 18-specific DNA probes for the areas flanking the breakpoints also detected RNA transcripts 6 kilobases in length in various cell types. The gene coding for these transcript (the bcl-2 gene) seems to be interrupted in most cases of follicular lymphomas carrying the t(14;18) chromosomal translocation.
1,854 citations
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.
Abstract: From an acute B-cell leukemia cell line, a DNA probe was obtained that was specific for chromosome 18 and flanked the heavy chain joining region of the immunoglobulin heavy chain locus on chromosome 14. This probe detected rearrangement of the homologous DNA segment in the leukemic cells and in follicular lymphoma cells with the t(14:18) chromosome translocation but not in other neoplastic or normal B or T cells. The probe appears to identify bcl-2, a gene locus on chromosome 18 (band q21) that is unrelated to known oncogenes and may be important in the pathogenesis of B-cell neoplasms with this translocation.
1,702 citations
TL;DR: It is determined that the bcl-2 (B-cell leukemia/lymphoma 2) gene is transcribed into three overlapping mRNAs, and the cDNA clones corresponding to the three bCl-2 transcripts contain at least two exons.
Abstract: We have determined that the bcl-2 (B-cell leukemia/lymphoma 2) gene is transcribed into three overlapping mRNAs, and we have cloned bcl-2 cDNA sequences. Sequence analysis of the bcl-2 cDNA clones and comparison of their sequences to their genomic counterparts indicate that the bcl-2 gene contains at least two exons. The three bcl-2 transcripts, which are 8.5, 5.5, and 3.5 kilobases (kb) long, overlap within the first exon, but only the 8.5-kb and 5.5-kb transcripts contain sequences of the second exon. The 8.5-kb and 5.5-kb transcripts seem to use different polyadenylylation sites. Sequence analysis of the cDNA clones corresponding to the 5.5-kb and 3.5-kb mRNAs indicates that the two bcl-2 transcripts carry two overlapping open reading frames, one of which is 717 nucleotides long and codes for a protein (bcl-2 alpha) of 239 amino acids and a molecular mass of 26 kDa, while the other codes for a protein of 205 amino acids (bcl-2 beta, molecular mass 22 kDa) that is identical to bcl-2 alpha except at the carboxyl terminus. The bcl-2 protein products in follicular lymphomas with or without bcl-2 rearrangements are identical to the normal bcl-2 products.
1,170 citations
TL;DR: The chromosomal breakpoint of chronic lymphocytic leukemia (CLL) cells of the B-cell type carrying the translocated long arms of chromosomes 11 and 14 [t(11;14) (q13;q32)] was cloned and a gene, named bcl -1, appears to be unrelated to any of the known retrovirus oncogenes described to date.
Abstract: The chromosomal breakpoint of chronic lymphocytic leukemia (CLL) cells of the B-cell type carrying the translocated long arms of chromosomes 11 and 14 [t(11;14) (q13;q32)] was cloned. The breakpoint was found to be within the joining segment of the human heavy chain locus on the translocated long arm of chromosome 14. A probe that is specific for chromosome 11 and that maps immediately 5' to the breakpoint on the 14q+ chromosome was isolated. The probe detected a rearrangement of the homologous genomic DNA segment in the parental CLL cells and also in DNA from a diffuse large cell lymphoma with the t(11;14) translocation. This rearranged DNA segment was not present in Burkitt lymphoma cells with the t(8;14) translocation or in nonneoplastic human lymphoblastoid cells. The probe can thus be used to identify and characterize a gene located on band q13 of chromosome 11 that appears to be involved in the malignant transformation of human B cells carrying the t(11;14) translocation. This gene, named bcl -1, appears to be unrelated to any of the known retrovirus oncogenes described to date.
669 citations
TL;DR: It is speculated that the t(11 ; 14) chromosome translocation in CLL may be sequence specific and may involve the recombination system for immunoglobulin gene segment (V–D–J) joining.
Abstract: The t(11;14) (q13;q32) chromosome translocation has been reported in diffuse small and large cell lymphomas and in chronic lymphocytic leukaemia (B-CLL) and multiple myeloma. Because chromosome band 14q32 is involved in this translocation, as well as in the t(8;14) (q24;q32) translocation of the Burkitt tumour, interruption of the immunoglobulin heavy-chain locus was postulated for this rearrangement. We have cloned the chromosomal joinings between chromosomes 11 and 14 and also between chromosomes 14 and 18, in B-cell tumours carrying translocations involving these chromosomes, and suggested the existence of two translocated loci, bcl-1 and bcl-2, normally located on chromosomes 11 (band q13) and 18 (band q21) respectively, involved in the pathogenesis of human B-cell neoplasms. The results indicate that in the leukaemic cells from two different cases of CLL, the breakpoints on chromosome 11 are within 8 nucleotides of each other and on chromosome 14 involve the J4-DNA segment. Because we detected a 7mer-9mer signal-like sequence with a 12-base-long spacer on the normal chromosome 11, close to the breakpoint, we speculate that the t(11;14) chromosome translocation in CLL may be sequence specific and may involve the recombination system for immunoglobulin gene segment (V-D-J) joining.
425 citations
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TL;DR: The basic components of the death machinery are reviewed, how they interact to regulate apoptosis in a coordinated manner is described, and the main pathways that are used to activate cell death are discussed.
Abstract: Apoptosis - the regulated destruction of a cell - is a complicated process. The decision to die cannot be taken lightly, and the activity of many genes influence a cell's likelihood of activating its self-destruction programme. Once the decision is taken, proper execution of the apoptotic programme requires the coordinated activation and execution of multiple subprogrammes. Here I review the basic components of the death machinery, describe how they interact to regulate apoptosis in a coordinated manner, and discuss the main pathways that are used to activate cell death.
7,255 citations
TL;DR: Overexpressed Bax accelerates apoptotic death induced by cytokine deprivation in an IL-3-dependent cell line and counters the death repressor activity of B cl-2, suggesting a model in which the ratio of Bcl-2 to Bax determines survival or death following an apoptotic stimulus.
6,193 citations
TL;DR: Bcl-2 and related cytoplasmic proteins are key regulators of apoptosis, the cell suicide program critical for development, tissue homeostasis, and protection against pathogens.
Abstract: Bcl-2 and related cytoplasmic proteins are key regulators of apoptosis, the cell suicide program critical for development, tissue homeostasis, and protection against pathogens. Those most similar to Bcl-2 promote cell survival by inhibiting adapters needed for activation of the proteases (caspases) that dismantle the cell. More distant relatives instead promote apoptosis, apparently through mechanisms that include displacing the adapters from the pro-survival proteins. Thus, for many but not all apoptotic signals, the balance between these competing activities determines cell fate. Bcl-2 family members are essential for maintenance of major organ systems, and mutations affecting them are implicated in cancer.
5,380 citations
TL;DR: The identification of critical control points in the cell death pathway has yielded fundamental insights for basic biology, as well as provided rational targets for new therapeutics.
4,741 citations
TL;DR: New insights into interactions among BCL-2 family proteins reveal how these proteins are regulated, but a unifying hypothesis for the mechanisms they use to activate caspases remains elusive.
Abstract: BCL-2 family proteins, which have either pro- or anti-apoptotic activities, have been studied intensively for the past decade owing to their importance in the regulation of apoptosis, tumorigenesis and cellular responses to anti-cancer therapy. They control the point of no return for clonogenic cell survival and thereby affect tumorigenesis and host-pathogen interactions and regulate animal development. Recent structural, phylogenetic and biological analyses, however, suggest the need for some reconsideration of the accepted organizational principles of the family and how the family members interact with one another during programmed cell death. Although these insights into interactions among BCL-2 family proteins reveal how these proteins are regulated, a unifying hypothesis for the mechanisms they use to activate caspases remains elusive.
4,246 citations