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)

A sensitive nitrocellulose filter assay that measures the retention of 125I single-stranded calf thymus DNA has been used to detect and purify DNA-binding proteins that retain a biological function from Rauscher murine leukemia virus. By consecutive purification on oligo (dT)- cellulose and DEAE-Bio-Gel columns and centrifugation in 10 to 30% glycerol gradients, RNA-dependent DNA polymerase has been separated from a second virion DNA-binding protein. The binding of this protein to DNA was strongly affected by NaCl concentration but showed little change in activity over a wide range of temperature or pH. After glycerol gradient purification, polyacrylamide gel electrophoresis of this protein showed one major band with a molecular weight of approximately 9,800. This protein binds about as well as to single-stranded Escherichia coli or calf thymus DNA or 70S type C viral RNA. The binding to 125I single-stranded calf thymus DNA is very efficiently inhibited by unlabeled single-stranded DNA from either E. coli or calf thymus and by 70S murine or feline viral RNA. Much larger amounts of double-stranded DNA are required to produce an equivalent percentage of inhibition. This protein, therefore, shows preferential binding to single-stranded DNA or viral RNA.
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PMID:Low-molecular- weight Rauscher leukemia virus protein with preferential binding for single-stranded RNA and DNA. 5 75

Lymphocytes from a common human leukemia, chronic lymphocytic leukemia, chronic lymphocytic leukemia, have a greatly enhanced capability of DNA repair and a concomitantly prolonged survival in vitro after damage to DNA. From these lymphocytes, we isolated and purified a DNA-binding protein with a molecular weight of 24,000. It binds tightly to both ultraviolet light (UV)-irradiated and single-stranded DNA. At 35 degrees it enhances the helix-coil transition of poly[d(A-T)] AND the UV-irradiated calf thymus DNA but is inefficient in ordinary native DNA. This protein also facilitates the rate of UV-endonuclease incision of UV DNA but does not induce any nicks by itself. This finding suggests that the protein may be involved in DNA repair by enhancing such activity, and also offers an explanation for our observation of increased DNA repair in chronic lymphocytic leukemia cells. When human metaphase chromosomes are exposed to the protein, it induces marked lengthening of chromatids suggesting that this protein may also act on complex chromosomes. By quantitative immunochemical determinations, such protein could not be found in lymphocyte extracts of three normal individuals.
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PMID:Some properties of a DNA-unwinding protein unique to lymphocytes from chronic lymphocytic leukemia. 111 55

Ultrastructural, flow cytometric, and molecular studies were performed on leukemia cells from bone marrow and pleural effusion of a 6-year-old boy diagnosed with undifferentiated (MO) leukemia, using routine histology and immunostains at diagnosis and relapse. Ultrastructurally, surface and/or intracellular ferritin particles were present on or in some blasts and the majority of blasts contained identifiable acid ferrocyanide reactive inorganic iron comparable to that seen in normal early erythroblasts. The cells lacked other evidence of differentiation, including diaminobenzidine-reactive or immunoreactive hemoglobin. Flow cytometric analysis of malignant cells showed a lack of lymphoid or myeloid markers. Anti-transferrin receptor antibody was positive on 93% of cells and antibody to glycophorin A reacted with 23% of cells. RNA blot analysis of leukemia cells with myeloperoxidase (MPO) showed an absence of appreciable levels of MPO mRNA. Chromosome analysis showed 51,XY, t(1;16)(p31;q24), +6, +10, +15, +19, +21. The oncogene c-myb, which is specifically expressed and regulated in hematopoietic cells and produces a DNA-binding protein responsible for myeloid differentiation, was found to be duplicated in the patient's tumor cells. Expression of c-jun, N-ras, c-myc, and p53 was normal. The data indicate that the malignant cells in this patient are of early erythroid lineage at diagnosis and relapse and that classification of cell lineage can be enhanced by ultrastructural Prussian blue staining. The failure of this otherwise undifferentiated leukemia to express or evolve into a myeloid phenotype is biologically and clinically distinct from previously described cases of erythroid and myeloid leukemia and may represent a previously unidentified phenotype which should be included in the spectrum of 'undifferentiated' childhood leukemia.
Leukemia 1991 Feb
PMID:Childhood undifferentiated leukemia with early erythroid markers and c-myb duplication. 170 34

The v-myb oncogene of avian myeloblastosis virus causes acute myelomonocytic leukemia in chickens and transforms avian myeloid cells in vitro. Its protein product p48v-myb is a nuclear, sequence-specific, DNA-binding protein which activates gene expression in transient DNA transfection studies. To investigate the relationship between transformation and trans-activation by v-myb, we constructed 15 in-frame linker insertion mutants. The 12 mutants which transformed myeloid cells also trans-activated gene expression, whereas the 3 mutants which did not transform also did not trans-activate. This implies that trans-activation is required for transformation by v-myb. One of the transformation-defective mutants localized to the cell nucleus but failed to bind DNA. The other two transformation-defective mutants localized to the cell nucleus and bound DNA but nevertheless failed to trans-activate. These latter mutants define two distinct domains of p48v-myb which control trans-activation by DNA-bound protein, one within the amino-terminal DNA-binding domain itself and one in a carboxyl-terminal domain which is not required for DNA binding.
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PMID:Transformation by v-myb correlates with trans-activation of gene expression. 216 May 80

Genetic studies have indicated that integration of retroviral DNA into the host genome depends on the presence of the inverted repeats at the free termini of the long terminal repeats on the unintegrated DNA and on the product of the 3' end of the pol gene (the integrase [IN] protein). While the precise function of the Moloney murine leukemia virus IN protein is uncertain, others have shown that it is a DNA-binding protein and functions in the processing of the inverted repeats prior to integration. By using site-directed mutagenesis, we cloned and expressed the IN protein in Escherichia coli. Crude extracts of total cellular protein were fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transferred to nitrocellulose filters, denatured in guanidine, renatured, and incubated with oligonucleotide probes. Single- and double-stranded oligonucleotides corresponding to the termini of unintegrated linear viral DNA were specifically bound by the IN protein in this assay. These data suggest that the role of the Moloney IN protein in the early steps of integration involves sequence-specific recognition of the DNA sequences found at the ends of the long terminal repeats.
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PMID:Sequence-specific binding of DNA by the Moloney murine leukemia virus integrase protein. 218 76

Nuclear extracts of cultured human cells contain multiple proteins that recognize specific sequence elements within the transcriptional control region of the human retrovirus, human T-cell leukemia virus type I (HTLV-I). Here we report the purification of host expression factor 1T (HEF-1T), a DNA-binding protein from human T-lymphocytes that binds to each of the three 21-base pair repeat enhancer elements in the proviral long terminal repeats of HTLV-I and the related virus, HTLV-II. HEF-1T is composed of two polypeptides of 41 and 59 kDa. We show that HEF-1T is distinct from a second protein, present in non-lymphoid cells, that binds to overlapping sites in and near the 21-base pair repeats. This second protein is composed of a single 47-kDa polypeptide and appears to be identical to the previously described transcription factor AP-2. A third protein, also distinct from HEF-1T, binds within the first repeat. The present results suggest that there may be multiple modes of HTLV-I promoter recognition involving distinct sets of cellular proteins.
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PMID:Interaction of cellular proteins with the human T-cell leukemia virus type I transcriptional control region. Purification of cellular proteins that bind the 21-base pair repeat elements. 233 23

Human cell lines that contain and express the gene encoding the adenovirus type 5 DNA-binding protein (Ad5 DBP) are very useful for the isolation of adenovirus mutants with an altered DBP. In order to obtain these cells, human 143 tk- cells were transfected, using the calcium phosphate technique, with plasmids containing the Ad5 DBP gene and the herpes simplex virus thymidine kinase (HSV tk) gene as a selectable marker. Characterization of several tk+ transformants revealed that these cells did contain the HSV tk gene, but in none of these cells could Ad5 DBP DNA sequences be detected. However, when 143 tk- cells were co-transfected with a plasmid containing the Ad5 DBP gene and another plasmid carrying early region E1, integration of the Ad5 DBP gene in chromosomal DNA could be detected. Integration of Ad5 DNA sequences was also observed when transfection was performed with plasmids containing the Ad5 DBP gene and the long terminal repeat of Moloney murine leukaemia virus. By employing a radioimmunoassay it could be shown that DBP-related proteins were synthesized in two of the cell lines containing the Ad5 DBP gene. Since both cell lines support the growth of the temperature-sensitive viral DBP mutant, H5ts125, at the non-permissive temperature, the DBP-related proteins expressed in these cells must be functional.
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PMID:Transformation of human 143 tk- cells with plasmids containing the gene encoding the adenovirus DNA-binding protein. 299 73

We have identified and analyzed a 27-nucleotide sequence (U5 repressive element, designated as U5RE) at the U5 region of the human T-cell leukemia virus type I (HTLV-I) long terminal repeat (LTR) which is required for HTLV-I basal transcriptional repression. The basal promoter strength of constructs that contained deletions in the U5 region of the LTR was analyzed by chloramphenicol acetyltransferase (CAT) assays following transfection of HeLa cells or Jurkat T-cells in the presence or absence of viral transactivator tax protein. We consistently observed a 2- to 5-fold increase in basal promoter activity when sequences between +277 to +306 were deleted. In vivo competition experiments suggested that the U5 DNA fragment from +269 to +295 contains a functional repressive element (U5RE). Using gel mobility shift assays, we have purified a highly enriched fraction that could specifically bind U5RE. This DNA affinity column fraction contained three major detectable proteins on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with silver staining: 110-, 80- and 70-kDa proteins. The 110-kDa protein appeared to be a novel DNA-binding protein whose characteristics are still obscure, while the 70- and 80-kDa proteins were shown to be related to the human autoantigen Ku, the Ku (p70/p80) complex, as demonstrated by amino acid sequencing and immunological analyses. As Ku is known to be involved in transcriptional regulation, the specific interaction of Ku with U5RE raises intriguing possibilities for its function in HTLV-I basal transcriptional repression.
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PMID:Autoantigen Ku protein is involved in DNA binding proteins which recognize the U5 repressive element of human T-cell leukemia virus type I long terminal repeat. 798 30

To analyze regulation of the human T-cell leukemia virus type I (HTLV-I) long terminal repeat (LTR), cell lines were generated from LTR-tax x LTR-beta-galactosidase (beta-Gal) doubly transgenic mouse fibroblastic tumors. The HTLV-I LTR directs expression of both the tax and lacZ genes, and Tax up-modulates both promoters in primary cells. However, once cells were transformed by tax, beta-Gal but not tax expression was suppressed. Supertransformation of these cells with v-src suppressed both beta-Gal and tax expression. This suppression was reversed by treatment with the tyrosine kinase inhibitor herbimycin A or protein kinase A inhibitor H8. Electrophoretic mobility shift assays demonstrated augmented binding in the R but not U3 region. This binding was competitively inhibited by a high-affinity CREB oligodeoxynucleotide and super-shifted with a specific CREB antibody. Treatment of cells with the cyclic AMP analog dibutyryl cyclic AMP also transiently increased the R region binding dramatically. In vitro DNase I footprint analysis identified a protein-binding sequence in the R region which corresponded with suppression. However, this target sequence lacked a conventional CREB-binding site. A 70.5-kDa DNA-binding protein was partially purified by affinity chromatography, along with a 49-kDa protein which reacted with CREB-specific sera. These data demonstrate that HTLV-I LTR suppression is associated with CREB factor binding in the R region, probably by direct interaction with a 70.5-kDa protein, and provide a novel mechanism for maintenance of viral latency.
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PMID:Transcriptional suppression of the human T-cell leukemia virus type I long terminal repeat occurs by an unconventional interaction of a CREB factor with the R region. 803 15

The 40-kDa nuclear protein Tax encoded by human T-cell leukemia virus type I (HTLV-I) can transcriptionally activate the interleukin 2 (IL-2) enhancer even in the presence of the immunosuppressant cyclosporin A, which inhibits the activation of the IL-2 enhancer by T-cell mitogens. We have identified a Tax-responsive element (TxRE) from -164 to -145 bp in the IL-2 enhancer which is sufficient to confer Tax responsiveness. A 45-kDa nuclear protein (TxRE-binding factor [TxREF]), present in Tax-expressing Jurkat cell lines but not in Jurkat cells without Tax, specifically interacts with the 5' TxRE sequence from -164 to -154. Deletion or mutation of this 5' TxRE sequence removes the binding of TxREF in vitro and dramatically reduces Tax activity in vivo. In addition, this site is responsible for the cyclosporin A-resistant expression of the IL-2 enhancer in the presence of Tax. Although the TxREF binding site contains an NF-kappa B like motif, UV cross-linking studies as well as gel retardation analysis reveal that TxREF is distinct from NF-kappa B. These results demonstrate that TxREF is a novel Tax-inducible DNA-binding protein and that TxRE plays a crucial role in mediating Tax-induced IL-2 gene expression.
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PMID:A cis element required for induction of the interleukin 2 enhancer by human T-cell leukemia virus type I binds a novel Tax-inducible nuclear protein. 841 48


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