Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mouse PIM-1 gene is involved in the pathogenesis of virally-induced mouse lymphomas. We have cloned and analyzed the human homologue of the mouse PIM-1 gene to investigate its role in human lymphoma and leukemia. Overlapping cDNA clones from a K562 (human erythroleukemia cell line) library were isolated and sequenced. The deduced amino acid sequence showed significant homology to a number of the protein kinases but did not have a transmembrane region. Genomic clones from the 380 cell line (human B cell leukemia) were analyzed. The PIM-1 transcript was found to derive from 5 Kb of genomic DNA. Six exons and five introns were identified. The promoter region has no TATA or CAAT boxes, but did have multiple potential Sp1 binding sites (CCGCCC). Studies of expression of this gene using Northern blots of human cell lines showed it to be transcribed primarily in B lymphoid and myeloid cell lines. The characterization of the human PIM-1 gene will allow the definition of its role in hemopoietic malignancies and in hematolymphoid differentiation.
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PMID:Characterization of the human PIM-1 gene: a putative proto-oncogene coding for a tissue specific member of the protein kinase family. 332 11

In order to measure beta1-SP1-glycoprotein (SP1), on RIA system by the 2-antibody method was established as a measuring method of the low concentration range. SP1 concentrations were measured by this method in the sera of women in early pregnancy, in the amniotic fluids of late pregnancy, in the sera of malignant tumour patients. Furthermore, SP1 concentrations in the sera of women in early pregnancy as well as E2, E3, progesterone and HCG concentrations in the same samples were measured, and correlations between them were examined. 1) The minimum sensitivity of this measuring system was 3ng/ml. The optimum concentration of samples was between 10 approximately 660ng/ml. 2) The correlation between the data obtained by this RIA method and the SRID method was as close as r = 0.9287. 3) SP1 concentrations in the sera of women in early pregnancy were 0.17 +/- 0.12 microgram/ml in the fifth week of pregnancy, showing an almost straight increase during the course of pregnancy, and were 31.62 +/- 3.20 microgram/ml in the 13th week of pregnancy. 4) SP1 concentrations in amniotic fluids were 1.09 approximately 2.20 microgram/ml and were equal to about 1% of SP1 concentrations in the sera of women in late pregnancy. SP1 concentrations in the sera of umbilical cord blood were 0.13 approximately microgram/ml, which were equal to about 0.1% of SP1 concentrations in the sera of women in late pregnancy. 5) SP1 was detected in all four samples of the choriocarcinoma patients' sera, and the concentrations were 25 approximately 2,600ng/ml. Sp1 was detected in 6 of the 15 samples of the cervical carcinoma patients' sera, and the detection rate was 40%. SP1 was detected in 3 of the 6 samples of the leukemia patients' sera and 1 of the 4 samples of the prostatic cancer patients' sera. SP1 detection rates and concentrations appeared to increase in the sera of cervical carcinoma and leukemia patients in accordance with the progress of the diseases. SP1 concentrations in the sera of women in early pregnancy were not correlative to measured E2 and E3 concentrations in the same samples, but there was a significant correlation with progesterone and HCG concentrations. The RIA method for measuring SP1, which we have established, is available for measuring SP1 in the low concentration range. The method is expected to be applied clinically, such as in examinations in early pregnancy, and will be available in fundamental studies such as attempts to measure the SP1 movement in malignant tumour patients, in cooperation with studies of the meaning of SP1 production at pregnancy.
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PMID:[Studies for a sensitive radioimmunoassay of beta1-Sp1-glycoprotein (SP1) (author's transl)]. 697 Jan 46

The human T-cell lymphotropic virus type I (HTLV-I)-encoded protein, Tax, is capable of trans-activating HTLV-I transcription by interacting with specific sequences in the HTLV-I long terminal repeat (LTR) which comprise an inducible enhancer containing three imperfect tandem repeats of a 21-bp sequence. There is no evidence that purified Tax can bind to DNA in the absence of cellular factors, suggesting that Tax most likely regulates transcription via interaction with cellular factors. Since HTLV-I is a documented agent of adult T-cell leukemia and tropical spastic paraparesis, disorders of the immune and nervous systems, respectively, characterization of cellular factors of lymphoid and neuroglial origin which interact with the 21-bp repeat elements is essential to understanding of the mechanisms involved in basal and Tax-mediated transcription in cells of immune and nervous system origin. Utilizing electrophoretic mobility shift (EMS) analyses, we have detected both 21-bp repeat-specific and glial cell-specific DNA-protein complexes. Several 21-bp repeat-specific DNA-protein complexes were detected when nuclear extracts derived from cells of lymphoid (Jurkat, SupT1, and H9), neuronal (IMR-32 and SK-N-MC), and glial (U-373 MG, Hs683, and U-118) origin were used in reactions with each of the three 21-bp repeat elements. In addition, a glial cell-specific DNA-protein complex was detected when nuclear extracts derived from U-373 MG, Hs683, and U-118 glial cell lines reacted with the promoter-distal and central 21-bp repeat elements. Furthermore, EMS analyses performed with nuclear extracts derived from lymphocytic and glial cell origin and a 223-bp fragment of the HTLV-I long terminal repeat encompassing the three 21-bp repeat elements (designated Tax-responsive elements 1 and 2, TRE-1/-2) have also resulted in the detection of glial cell type-specific DNA-protein complexes. Competition EMS analyses with oligonucleotides containing transcription factor binding site sequences indicate the involvement of a cyclic AMP response element binding protein in the formation of DNA-protein complexes which form with all three 21-bp repeat elements and the glial cell-specific DNA-protein complex as well as the involvement of Sp1 or an Sp1-related factor in the formation of the 21-bp repeat III-specific DNA-protein complexes.
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PMID:Identification of human T-cell lymphotropic virus type I 21-base-pair repeat-specific and glial cell-specific DNA-protein complexes. 820 34

The Tax protein, encoded by the human T-cell leukemia virus type I, is a potent activator of viral and cellular gene transcription. Tax does not bind DNA directly but appears to trans-activate through an interaction with host-cell transcription factors that recognize sequences within the promoters of Tax-responsive genes. Cellular transcriptional activators implicated in mediating Tax trans-activation include members of the activating transcription factor/cAMP response element binding protein (ATF/CREB) family of proteins, serum response factor, Fos-Jun, and NF-kappa B. Recent evidence suggests that Tax may stimulate human T-cell leukemia virus type I transcription, at least in part, through enhanced binding of ATF/CREB proteins to their recognition elements within the Tax-responsive 21-bp repeats of the viral promoter. In this report, we demonstrate that Tax also enhances the site-specific DNA binding activity of serum response factor and Fos-Jun and modestly enhances the binding of the NF-kappa B subunits, p50 and p65. We also show that Tax increases the DNA binding activity of the eukaryotic transcription factors ATF-1, Sp1, and GAL4. These results are consistent with the finding that Tax is highly pleiotropic and suggest that Tax trans-activation may involve enhancement in the DNA binding activity of target transcriptional regulatory proteins. In addition, we show that the mechanism of Tax-enhanced DNA binding activity does not involve an alteration in the redox state of the target protein.
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PMID:Pleiotropic effect of the human T-cell leukemia virus Tax protein on the DNA binding activity of eukaryotic transcription factors. 834 48

The human immunodeficiency virus (HIV) type 1 long terminal repeat (LTR) contains binding sites for nuclear factor kappa B (NF-kappa B) and the constitutively expressed transcription factor Sp1, both of which are highly conserved in HIV and simian immunodeficiency virus isolates. To delineate the effects of these motifs on the replicative capacity of HIV and to explore the possibility of extending the virus host range, known heterologous enhancer/promoters were inserted into the HIV-1 LTR in place of the NF-kappa B and Sp1 binding sites. The effects of these substitutions on viral replication in transfected HeLa cells and on HIV infection of human peripheral blood lymphocytes or continuous T-leukemia cell lines were evaluated. HIVs in which the NF-kappa B/Sp1 enhancer plus the downstream TATA element were replaced with heterologous enhancer/promoters were also constructed. Viruses containing the human cytomegalovirus immediate-early enhancer exhibited infectious kinetics similar to that of wild-type HIV in activated human peripheral blood lymphocytes and AA2 cells but replicated less efficiently in H9 and CEM cells. These studies indicate that heterologous enhancer elements are capable of restoring Tat responsiveness to the HIV LTR in the context of directing reporter gene expression as well as in the production of infectious progeny virions.
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PMID:Human immunodeficiency viruses containing heterologous enhancer/promoters are replication competent and exhibit different lymphocyte tropisms. 841 44

The involvement of Sp1 in regulating cell proliferation in myeloid leukemia cells was determined by measuring the levels and DNA binding activity of Sp1 in TF-1 cells, a human erythroleukemia cell line dependent on granulocyte/macrophage colony-stimulating factor (GM-CSF) for viability and cell growth. DNA binding of Sp1 to a specific double-stranded oligodeoxynucleotide was increased markedly in a dose-dependent manner in proliferating cells in response to GM-CSF compared with growth-arrested or apoptotic cells. Competition experiments and mobility shift interference assays with antibodies against Sp1 as well as wild-type or mutant p53 indicated that GM-CSF-inducible DNA-binding complexes contained both Sp1 and p53 and that these heterocomplexes bound to both p53- and Sp1-binding sequences with high affinity. Immunoprecipitation of nuclear extracts with a p53 antibody indicated that Sp1 was associated as a heterocomplex with p53. Formation of this complex was dependent on the level of p53 since p53 was more abundant in proliferating cells and decreased upon induction of growth arrest and apoptosis by withdrawal of GM-CSF while Sp1 levels remained unchanged. These results suggest that the association of Sp1 with p53 may represent a novel mechanism of growth regulation in cytokine-dependent leukemia cells.
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PMID:Induction of Sp1-p53 DNA-binding heterocomplexes during granulocyte/macrophage colony-stimulating factor-dependent proliferation in human erythroleukemia cell line TF-1. 846 13

The human c-sis proto-oncogene promoter is transactivated by the human T-cell leukemia virus type 1 Tax protein in human Jurkat T-cells. Transactivation was >7-fold in Jurkat cells stably expressing the Tax protein (Jurkat-Tax) than in Jurkat E6.1 cells and was further enhanced in Jurkat-Tax cells stimulated with 12-O-tetradecanoylphorbol-13-acetate and the calcium ionophore, ionomycin. Deletion analysis showed that a 167-base pair promoter fragment retained full Tax responsiveness. Insertion of this minimal Tax-responsive region into a heterologous, minimal promoter resulted in approximately a 7-fold increase of transcriptional activation in the presence of Tax. Linker-scanning insertion analysis of this region identified Tax-responsive elements at nucleotides -64 to -45 (TRE1) and -34 to -15 (TATA box region). TRE1 contains a consensus binding site for the Sp family of transcription factors. The TATA box region corresponds to the TATA box and its 3'-neighboring sequence. Gel-shift and antibody supershift analysis of TRE1-binding proteins in unstimulated Jurkat E6.1 and Jurkat-Tax nuclear extracts identified Sp1 and Sp3 as the main TRE1 binding factors. Nuclear extracts from stimulated Jurkat E6.1 and Jurkat-Tax cells identified an additional TRE1 binding factor, Egr-1. These studies define a novel mechanism whereby Tax transactivates the c-sis promoter.
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PMID:c-sis/PDGF-B promoter transactivation by the Yax protein of human T-cell leukemia virus type 1. 866 78

The human chromosome 21 AML1 gene is expressed predominantly in the hematopoietic system. In several leukemia-associated translocations AML1 is fused to other genes and transcription of the fused regions is mediated by upstream sequences that normally regulate the expression of AML1. The 5' genomic region of AML1 was cloned and sequenced. The two 5' untranslated regions (UTRs) previously identified in AML1 cDNAs were located in this region and the distance between them was established. The distal 5' UTR maps over 7 kb upstream of the proximal one. Using primer extension with mRNA, transcription start sites were identified at two distinct sites above these 5' uTRs. Sequence analysis revealed the absence of a TATA motif and the presence of Sp1, PU.1, Oct, CRE, Myb, Ets, and Ets-like binding sites in both upstream regions. Several initiator elements (Inr) that overlap the transcription start sites were also identified. These proximal and distal upstream regions and their deletion mutants were cloned in front of a luciferase reporter gene and used in transfection assays. We demonstrate that both upstream regions function as promoters in hematopoietic (Jurkat) and nonhematopoietic (HEK) cell lines. The activity of both promoters was orientation dependent and was enhanced, in a cell-type specific manner, by a heterologous enhancer sequence. These results indicate that additional control elements, either negative or positive, regulate the tissue-specific expression of AML1.
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PMID:Expression of the human acute myeloid leukemia gene AML1 is regulated by two promoter regions. 870 Aug 62

The human T-cell leukemia virus type 1 (HTLV-1) promoter contains three copies of an imperfect 21-bp repeat called Tax-responsive element (TRE1). To examine the role of individual TRE1 sequences in basal transcription of the HTLV-1 promoter, site-directed mutations were generated in all possible combinations of one, two, or all three TRE1 elements in the viral long terminal repeat (LTR) and tested in vivo for transcriptional activity. Mutation of the middle TRE1 resulted in the greatest reduction in basal activity. Electrophoretic mobility shift analysis demonstrated that the protein complexes bound to each of the three TRE1 sequences were not identical. The complexes formed with the TATA-distal and middle TRE1s were dependent on the core cyclic AMP response element (CRE) found in all three TRE1s, while the cellular transcription factor Sp1 bound the TATA-proximal TRE1 in a CRE-independent manner. Sp1 binding produced a footprint on the viral LTR which covered the 5' region of the proximal TRE1. Mixing experiments demonstrated that the bindings of CREB and Sp1 to the proximal TRE1 were mutually exclusive. Sp1 was able to activate transcription both from the complete LTR and from the proximal TRE1 alone. These studies demonstrate that the TRE1 elements in the HTLV-1 LTR are functionally nonequivalent and suggest that Sp1 can influence HTLV-1 basal transcription.
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PMID:Function of the human T-cell leukemia virus type 1 21-base-pair repeats in basal transcription. 898 55

Differentiation generally leads to cell cycle arrest. Human leukemia HL60 cells respond to the presence of 1,25-dihydroxyvitamin D3 (1,25D3) by expressing a number of markers of the monocyte/macrophage phenotype and become arrested predominantly in the G1 phase of the cell cycle. We have recently reported a series (A) of 1,25D3-resistant variants of HL60 cells which proliferate in the presence of 1,25D3 and do not express differentiation markers (Exp. Cell Res. 224, 312, 1996). We now describe another series (B) of such variants, which differ from A series cells grown in similar concentrations of 1,25D3 in that they express the CD14 antigen and nonspecific esterase, characteristic of the monocyte, while continuing to proliferate and they develop hypotetraploid DNA (4C) content at higher concentrations of ambient 1,25D3 than the A series cells. Cells in the B series with 4C DNA content (100B and 200B) also differed from the A series 4C cells by the absence of DNA binding by the full-length Sp1 transcription factor. However, B series cells resembled the A series cells in exhibiting faster growth rates than the parental HL60 cells and showed high levels of vitamin D receptor and retinoid receptor X proteins. These results show that the initial steps in the 1,25D3 signaling pathway are intact in B series resistant cells and lead to the appearance of early markers of monocytic differentiation. However, the progression to subsequent events which comprise terminal differentiation and cell cycle arrest is halted during the adaptation to the presence of 1,25D3 in these cells. Thus, the availability of these variant cells should provide a system for studying the link between differentiation and cell cycle arrest.
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PMID:Uncoupling of cell cycle arrest from the expression of monocytic differentiation markers in HL60 cell variants. 916 15


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