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)

The human lymphocyte-specific tyrosine kinase gene, lck, is transcribed from two distinct promoters, resulting in two classes of transcripts (type I and II) differing in their 5' untranslated regions. The steady-state levels of the type I and II lck transcripts were measured in a variety of lymphoid and non-lymphoid human tumor cell lines by S1 nuclease mapping and by a sensitive assay system using the polymerase chain reaction. Human thymocytes and all the leukemic T cell lines tested express both type I and II lck transcripts, albeit at different relative levels. Peripheral blood T cells express mainly type II lck transcripts, whereas two colonic carcinoma lines, COLO 201 and COLO 205, express exclusively type I lck transcripts. Treatment of the leukemic T cell lines, P30/OKUBO and Jurkat, by the phorbol esters tetradecanoylphorbol acetate (TPA) or phorbol dibutyrate (PDB) results in the down-regulation of the type I, and the up-regulation of the type II, lck transcript levels. The effect of PDB on the in vitro differentiation of Jurkat cells, and the expression of lck transcripts, is reversible. The modulation of lck transcript levels in TPA-treated Jurkat cells is not due to differential RNA stability, suggesting that the two lck promoters are utilized differentially during T cell differentiation. The leukemic T cell line, Jurkat, may thus serve as a model for the elucidation of molecular mechanisms that regulate lck transcription and T cell differentiation.
 ...
PMID:Differential expression of two classes of lck transcripts upon phorbol ester treatment of human leukemic T cells. 191 68

The human T-cell- or lymphocyte-specific gene, lck, encodes a tyrosine kinase and is a member of the src family. In this report we demonstrate that there are two classes of human lck transcripts (types I and II), containing different 5'-untranslated regions, which are expressed from two distinct promoters. No apparent sequence similarity was observed between the 5'-flanking regions of the two promoters. The expression of lck in human T-cell leukemia and carcinoma cell lines and in human peripheral blood T lymphocytes was examined by S1 nuclease and primer extension mapping and by Northern (RNA) blot analysis of total cellular RNA. The following results were obtained. (i) Two RNA start sites in the downstream promoter were used to generate type I transcripts. (ii) The major human type I start site has not been described for the mouse. (iii) At least five RNA start sites in the upstream promoter were used to generate type II transcripts. (iv) In T cells and in two colon carcinoma cell lines, type II transcripts were present in higher amounts than type I transcripts. (v) In T cells treated with phytohemagglutinin, tetradecanoylphorbol acetate, and cyclosporin A, the modulation of lck expression was associated primarily with changes in levels of type II transcripts. The above results suggest that the two human lck promoters are utilized differentially and may be regulated independently during certain physiological states.
 ...
PMID:Structure of the two promoters of the human lck gene: differential accumulation of two classes of lck transcripts in T cells. 278 74

p56lck, a member of the src family of cytoplasmic tyrosine protein kinases, is expressed primarily in lymphoid cells. Previous RNase protection data demonstrated the existence of at least two lck mRNAs (type I and type II) with different 5' untranslated regions in most T cells. These have been found here to arise from two separate promoters. S1 nuclease analysis and primer extension were used to locate the site of initiation of type I lck mRNA. The nucleotide sequence of the region upstream of this start site contains no classical promoter motifs. A cDNA clone of type II lck mRNA was isolated. The promoter of this mRNA must be more than 10 kilobases upstream of the type I promoter region. In two murine thymoma cell lines, LSTRA and Thy19, lck is expressed at elevated levels as a result of Moloney murine leukemia virus retrovirus promoter insertion. p56lck is encoded in these cells by a hybrid virus-lck mRNA containing the 5' untranslated region of Moloney virus mRNA. The structures and the sites of integration of the proviruses upstream of lck in these cells were examined by molecular cloning and Southern analysis. A truncated and rearranged provirus, flanked by 554 nucleotides (nt) of duplicated cellular sequences, was found 962 nt upstream of the start site for type I lck mRNA in LSTRA cells. What appears to be a Moloney mink cytopathic focus-forming provirus was found between 584 to 794 nt upstream of the start site for type I lck mRNA in Thy19 cells. Thus in both tumor cell lines, viral DNA is present between the promoters for type I and type II lck mRNAs. Comparison of the sequences of the 5' ends of the lck and c-src genes suggests that divergence of these two genes involved exon shuffling and that a homolog of the neuronal c-src(+) exon is not present in lck.
 ...
PMID:Transcriptional activation of lck by retrovirus promoter insertion between two lymphoid-specific promoters. 284 26