Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.1 (S1 nuclease)
 3,660 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recurring chromosomal translocations are frequently seen in cancers, especially in leukemias and lymphomas. The genes affected by these chromosomal translocations appear to play an important role in oncogenesis. The mechanism underlying the formation of chromosomal translocation is a subject under extensive study. In chromosomal translocations involving the Ig and TCR loci, complete heptamer-spacer-nonamer signal motifs are usually present at the break of the Ig and TCR genes, indicating the involvement of V-D-J recombinase(s). On the other hand, in only about 50% of the cases signal motif sequences have been found at the break in the other participating chromosome, suggesting that different mechanisms may be involved in the scission of the corresponding chromosome. Here we report the identification of an oligopurine/oligopyrimidine DNA in the t(10;14) breakpoint cluster region associated with T-cell acute lymphoblastic leukemia. S1 nuclease mapping revealed multiple S1 hypersensitive sites in the oligopurine/oligopyrimidine DNA. These data suggest a role for oligopurine/oligopyrimidine sequences (non-B DNA) in the formation of chromosomal translocation.
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PMID:S1 nuclease hypersensitive sites in an oligopurine/oligopyrimidine DNA from the t(10;14) breakpoint cluster region. 174 Dec 51

We produced the T cell hybridoma D9C1.12.17 by fusing an IL-4-producing T cell clone D9.1Hi with the AKR thymoma BW5147. The resulting hybridoma produced IL-2 as well as IL-4 even though none of the parental cells produced IL-2 after stimulation with Con A. The production of IL-2 was confirmed at the mRNA level by using an S1 nuclease protection assay. Further analysis indicated that Con A-induced IL-2 production was a common phenomenon among T cell hybridomas derived from this fusion. Although BW5147 does not produce detectable lymphokines after Con A stimulation, this line was able to produce IL-2, granulocyte-macrophage colony stimulating factor, and small amounts of IL-3 and IFN-gamma when stimulated with calcium ionophore and phorbol ester. The latter agents are thought to mimic the activating signal(s) delivered through the Ag:MHC TCR. This observation indicates that BW5147 has the ability to produce lymphokines but may lack component(s) which couple the extracellular signal to lymphokine production, and suggests that in T cell hybridomas, part of the spectrum of lymphokines produced may be contributed by BW5147.
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PMID:The AKR thymoma BW5147 is able to produce lymphokines when stimulated with calcium ionophore and phorbol ester. 312 29

To ensure that the mature T cell repertoire is MHC-restricted yet not autoreactive, cortical thymocytes that express low levels of the TCR/CD3 complex along with CD4 and CD8 (double positive cells) are subjected to positive and negative selection. Surviving cells lose either CD4 or CD8 (single positive cells) and are located primarily in the thymic medulla. bcl-2, a novel proto-oncogene that promotes cell survival by inhibiting programmed cell death (apoptosis), may be an important protein in regulating cell survival during thymocyte development. We have examined the expression of bcl-2 during T cell development by using human thymocytes. Consistent with previous studies, human thymic tissue sections stained for bcl-2 revealed occasional bcl-2+ cells within the thymic cortex and intense staining of virtually all medullary thymocytes. More quantitative western blot analysis and S1 nuclease protection assay revealed that single positive thymocytes contained approximately 2 to 3 times the level of bcl-2 protein and 3 to 4 times the level of bcl-2 mRNA as double positive thymocytes. Flow cytometric analysis of purified double positive thymocytes revealed that minimal amounts of bcl-2 protein was in fact detectable in most cells, although a small subpopulation (10-20%) contained higher levels. In contrast, brighter staining for bcl-2 was observed in virtually all single positive thymocytes. Surprisingly, CD4-CD8- thymocytes (both CD3- and CD3+) expressed the same amount of bcl-2 as did the single positive thymocytes. Because a large percentage of CD3-CD4-CD8- cells are cycling, we examined the effect of mitogenic stimulation on bcl-2 expression by double positive thymocytes by using western blot analysis. bcl-2 expression in double positive thymocytes could not be induced by cell cycle entry following stimulation with PMA and ionomycin. Our data demonstrate that bcl-2 expression is biphasic during T cell development. Both CD3-CD4-CD8- and CD3+CD4+ and CD3+CD8+ thymocytes express high levels of bcl-2. Therefore, diminished bcl-2 expression in double positive thymocytes seems to be the result of specific down-regulation in order to facilitate the selection CD4+CD8+ thymocytes.
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PMID:bcl-2 proto-oncogene expression during human T cell development. Evidence for biphasic regulation. 832 41