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)

Using a polymerization inhibition assay, we have purified a small, heat stable protein that physically interacts with tubulin dimers and increases the catastrophe rate of microtubules. Sequence analysis identified this protein as oncoprotein 18 (Op18)/stathmin, a conserved phosphoprotein that is highly expressed in leukemia cells. Immunodepletion experiments in Xenopus egg extracts showed that Op18/stathmin is involved in physiological regulation of mitotic microtubule dynamics. Op18/stathmin is a microtubule regulator that preferentially interacts with unpolymerized subunits. It is a candidate for increasing the microtubule catastrophe rate in mitosis and might also regulate microtubule dynamics in response to external signals.
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PMID:Identification of a protein that interacts with tubulin dimers and increases the catastrophe rate of microtubules. 859 48

HTLV-I virus is as etiological agent of adult T-cell leukemia (ATL). The virus encodes Tax regulatory protein, which induces malignant transformation of the T lymphocytes. Tax increases the expression of cell protooncogenes as well as lymphokines, among others IL-2 and its receptor. This protein induces autocrine proliferation of T lymphocytes, which is probably the main cause of their transformation. Tax represses the human beta-polymerase gene enzyme involved in host cell DNA repair, and then irreversible damage is effected in the T lymphocyte genome. Moreover, this regulatory protein cooperates with Rex phosphoprotein, stabilizing cell mRNA, which originate as the result of Tax protein activity. The regulatory proteins of HTLV-I virus influence the transcription of some cell genes and their products and in this way induce malignant transformation.
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PMID:[The role of the HTLV-I virus in transformation of T lymphocytes]. 867 23

Mast cells (MC) can be stimulated to secrete by cross-linking immunoglobulin E bound to specific surface receptors, as well as in response to polycationic molecules such as substance P and compound 48/80. The antiallergic drug disodium cromoglycate (cromolyn) inhibited MC secretion and rapidly incorporated phosphate into a 78 kDa protein, speculated to be its mode of action. This protein was purified by single and two-dimensional gel electrophoresis, and was shown to be phosphorylated primarily on serine residues by protein kinase C. Partial amino acid sequencing of two generated fragments was identical to that of portions of mouse moesin, a member of the band 4.1 superfamily of proteins, with no definitive function known to date. Polyclonal antibodies raised against the rat basophil leukemia cell moesin cDNA expressed in Escherichia coli immunoprecipitated the 78 kDa phosphoprotein quantitatively, and immunocytochemistry localized it to the plasma membrane. Reversible phosphorylation of this 78 kDa phosphoprotein could affect its possible cytoskeletal binding through which it may regulate stimulus-secretion coupling in MC.
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PMID:Characterization of the 78 kDa mast cell protein phosphorylated by the antiallergic drug cromolyn and homology to moesin. 868 95

We examined the expression of an oncofetal 65-kDa phosphoprotein, termed p65, in patients with lymphocytic and granulocytic leukemia. This protein was previously identified in rat fetal tissues and in epithelial cancers of rat and human origin. Using the anti-p65 monoclonal antibodies MB2 and MF11 in a double-antibody sandwich enzyme-linked immunosorbent assay (ELISA), we analyzed the expression of the protein in sera of 80 normal, healthy controls and in 61 patients with benign, nonneoplastic diseases. We established that the upper level of normal p65 concentration is 115 U/ml p65 (mean plus two standard deviations above the mean in a control group). We also analyzed p65 levels in sera of 71 patients with leukemia in different stages of development. The level of p65 was well above normal in 95% of acute lymphocytic leukemia (ALL; 19 cases), 83% of acute myeloblastic leukemia (AML; 23 cases), 37% of chronic lymphocytic leukemia (CLL; 19 cases), and 30% of chronic myelogenous leukemia (CML; 10 cases). MB2 monoclonal antibodies were used for immunocytochemical staining of isolated lymphocytes from normal peripheral blood and from blood of leukemic patients (in 12 CLL patients, the p65 positivity was 83%, in 2 ALL patients, 100%, and in 4 AML patients, 75%). Our data suggest that p65 protein may be of use as a tumor marker in leukemia.
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PMID:Expression of an oncofetal 65-kDa phosphoprotein in lymphocytic and granulocytic leukemias. 893 33

The cell cycle has been the object of extensive studies for the past years. A complex network of molecular interactions has been identified. In particular, a class of cell cycle inhibitory proteins has been cloned and characterized but details of the molecular mechanism of their action have yet to be resolved. These inhibitors regulate the progression through G1 and the G1/S transition via the inhibition of the cyclin-dependent kinase (Cdk) activity. The potential function of these negative regulators as tumor suppressors provides new insights into the link between the cell cycle and oncogenesis. p27 is a potent inhibitor of Cdks. In quiescent cells p27 accumulates without an increase in mRNA or protein synthesis. Cell cycle regulation of p27 levels, both in normal and transformed human cells, occurs via the ubiquitin-proteasome pathway and, compared to proliferating cells, quiescent cells contain a far lower amount of p27 ubiquitinating activity. The specific proteolysis of p27 is probably involved in the pathway of activation of Cdks. p27 is a phosphoprotein and its phosphorylation is cell cycle regulated. Often phosphorylation is a signal for ubiquitination. p27 is phosphorylated exclusively on serine by Erk1 and almost exclusively on threonine by Cdk1 in in vitro experiments. This finding raises the question of whether and how phosphorylation by these kinases is involved in the process of p27 proteolysis.
Leukemia 1997 Mar
PMID:Regulation of the cyclin-dependent kinase inhibitor p27 by degradation and phosphorylation. 906 71

Transcription factor Sp1 is a phosphoprotein whose level and DNA binding activity are markedly increased in doxorubicin-resistant HL-60 (HL-60/AR) leukemia cells. The trans-activating and DNA binding properties of Sp1 in HL-60/AR cells are stimulated by cAMP-dependent protein kinase (PKA) and PKA agonists and inhibited by PKA antagonists as well as by the PKA regulatory subunit. Reporter gene activity under the control of the Sp1-dependent SV40 promoter is stimulated in insect cells transiently expressing Sp1 and PKA, and the DNA binding activity of recombinant Sp1 is activated by exogenous PKA in vitro. These results indicate that Sp1 is a cAMP-responsive transcription factor and that Sp1-dependent genes may be modulated through a cAMP-dependent signaling pathway.
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PMID:Modulation of transcription factor Sp1 by cAMP-dependent protein kinase. 926 Nov 18

Oncoprotein 18 (Op18) is a major cystolic phosphoprotein constituent of leukemia cells. There is cumulative evidence that suggests a role for Op18 in integrating signals from diverse pathways involved in cell growth. Op18 phosphorylation is induced with proliferation in a variety of cell types, and is essential for cell cycle progression. In this study we analyzed the level of unphosphorylated Op18 and of its major phosphorylated forms, Op18a and Op18b, in a series of 177 childhood acute leukemias by means of quantitative two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). Op18 phosphorylation was significantly correlated with the white blood count at the time of diganosis, and with a high percentage of cells in the S phase. Our findings suggest that strategies to inhibit Op18 expression or phosphorylation may be effective in inhibiting leukemia cell proliferation.
Leukemia 1997 Oct
PMID:Quantitative analysis of Op18 phosphorylation in childhood acute leukemia. 932 90

The AML1-CBFbeta transcription factor complex is essential for the definitive hematopoiesis of all lineages and is the most frequent target of chromosomal rearrangements in human leukemia. In the t(8;21) translocation associated with acute myeloid leukemia (AML), the AML1(CBFA2/PEBP2alphaB) gene is juxtaposed to the MTG8(ETO/CDR) gene. We show here that the resultant AML1-MTG8 gene product specifically and strongly interacts with an 85-kDa phosphoprotein. Molecular cloning of cDNA indicated that the AML1-MTG8-binding protein (MTGR1) is highly related to MTG8 and similar to Drosophila Nervy. Comparison of amino acid sequences among MTGR1, MTG8, and Nervy revealed four evolutionarily conserved regions (NHR1 to NHR4). Ectopic expression of AML1-MTG8 in L-G murine myeloid progenitor cells inhibits differentiation to mature neutrophils and induces cell proliferation in response to granulocyte colony-stimulating factor (G-CSF). Analysis with C-terminal deletion mutants of AML1-MTG8 indicated that the region of 51 residues (488 to 538), which contains NHR2, is essential for the induction of G-CSF-dependent cell proliferation. Immunoprecipitation analysis indicates that this region is required for AML1-MTG8 to form a stable complex with MTGR1. Overexpression of MTGR1 stimulates AML1-MTG8 to induce G-CSF-dependent proliferation of L-G cells and to interfere with AML1-dependent transcription. These results suggest that AML1-MTG8 could function as a complex with MTGR1 and that the complex might be important in promoting leukemogenesis.
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PMID:The AML1-MTG8 leukemic fusion protein forms a complex with a novel member of the MTG8(ETO/CDR) family, MTGR1. 944 81

The Tax transactivator protein of human T-cell leukemia virus type 1 (HTLV-1) plays a central role in the activation of viral gene expression. In addition, Tax is capable of activating the expression of specific cellular genes and is involved in the transformation of T-lymphocytes resulting in the development of adult T-cell leukemia. Tax is a phosphoprotein that colocalizes in nuclear bodies with RNA polymerase II, splicing complexes, and specific transcription factors including members of the ATF/CREB and NF-kappaB families. In this study, we identified adjacent serine residues at positions 300 and 301 in the carboxy terminus of Tax as the major sites for phosphorylation. Phosphorylation of at least one of these serine residues is required for Tax localization in nuclear bodies and for Tax-mediated activation of gene expression via both the ATF/CREB and NF-kappaB pathways. Introduction of amino acid substitutions which are phosphoserine mimetics at positions 300 and 301 restored the ability of a phosphorylation-defective Tax mutant to form nuclear bodies and to activate gene expression. These studies define sites for regulatory phosphorylation events in Tax which are critical for its ability to activate gene transcription.
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PMID:Phosphorylation of the human T-cell leukemia virus type 1 transactivator tax on adjacent serine residues is critical for tax activation. 984 80

The ectopic expression of LMO1 or LMO2 in T cell acute leukaemias resulting from chromosomal translocations t(11;14)(p15;qll) or t(11;14)(p13;q11) respectively in a causal factor in tumorigenesis. LMO1 has been found as a heterodimer with a 46 Kd protein in a T cell line derived from a childhood T-acute leukaemia. This 46 Kd protein is the LIM-binding protein LDB1/NLI. The latter is a phosphoprotein and binds to LMO1 in its phosphorylated state and essentially all the LMO1 and LDB1 protein in the T cell line is part of the complex. Therefore, the LMO1-LDB1 interaction is likely to be involved in tumorigenesis after LMO1 is ectopically expressed following chromosomal translocation in T cells prior to development of acute leukaemias.
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PMID:The LMO1 and LDB1 proteins interact in human T cell acute leukaemia with the chromosomal translocation t(11;14)(p15;q11). 987 35


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