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A. Tobler - One of the best experts on this subject based on the ideXlab platform.
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Cytosine demethylation of the proteinase-3/Myeloblastin primary granule protease gene during phagocyte development
Leukemia, 1999Co-Authors: M Lübbert, A. Tobler, M DaskalakisAbstract:Proteinase-3/Myeloblastin (Mbn) is a neutral serine protease and a major constituent of the primary granules of myeloid cells. It can degrade extracellular matrix proteins and has been discussed as a key factor for the initiation of terminal differentiation in promyelocytic cells. Regulation of Mbn closely parallels that of another major primary granule protein, myeloperoxidase (MPO). We examined the expression and DNA methylation of Mbn in a model of in vitro differentiation of CD34^+ enriched peripheral blood progenitor cells (PBPCs), and in various other myeloid and non-myeloid tissues. Mbn mRNA was undetectable in uncultured PBPCs but was upregulated during their in vitro differentiation. Its expression was enhanced in the presence of G-CSF. Mbn expression was also detected in several myeloid cell lines but not in mature granulocytes, monocytes and macrophages. Partial demethylation at a CpG site within Mbn intron 1 (analyzed by restriction with Sma I) was observed during continued in vitro differentiation of PBPCs. This site was fully demethylated in mature granulocytes, monocytes and macrophages. Variable methylation of this site and a second Sma I site located upstream of the putative Mbn promoter region was present in other myeloid and non-myeloid tissues examined.
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Myeloblastin/proteinase 3 belongs to the set of negatively regulated primary response genes expressed during in vitro myeloid differentiation.
Biochemical and biophysical research communications, 1994Co-Authors: Tao Chen, R. W. Meier, Andrew Ziemiecki, Martin F. Fey, A. ToblerAbstract:Regulation of Myeloblastin expression was studied during myeloid differentiation of HL60 cells and compared with that of myeloperoxidase. Induction towards the monocytic pathway of differentiation caused a rapid, marked and parallel down-regulation of both transcripts which were insensitive to cycloheximide. Thus, Myeloblastin is directly regulated and, similarly to myeloperoxidase, belongs to the set of primary response genes. Nuclear run-on experiments and RNA half-life determinations revealed that Myeloblastin regulation was at both the transcriptional and posttranscriptional levels.
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a Myeloblastin proteinase 3 cdna clone identifies a bglii and a pvuii restriction fragment length polymorphism
Human Genetics, 1993Co-Authors: J. Schwaller, T. Chen, M. F. Fey, A. ToblerAbstract:A Myeloblastin/proteinase-3 (MBN/PR-3) cDNA probe detects two bi-allelic (BglII, PvuII) DNA polymorphisms. These restriction fragment length polymorphisms provide new genetic markers on chromosome 19.
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A Myeloblastin/proteinase-3 cDNA clone identifies a BglII and a PvuII restriction fragment length polymorphism.
Human Genetics, 1993Co-Authors: J. Schwaller, T. Chen, M. F. Fey, A. ToblerAbstract:A Myeloblastin/proteinase-3 (MBN/PR-3) cDNA probe detects two bi-allelic (BglII, PvuII) DNA polymorphisms. These restriction fragment length polymorphisms provide new genetic markers on chromosome 19.
Yvon E. Cayre - One of the best experts on this subject based on the ideXlab platform.
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Myeloblastin is an Myb target gene: mechanisms of regulation in myeloid leukemia cells growth-arrested by retinoic acid
Blood, 2001Co-Authors: Pierre G. Lutz, Anne Houzel-charavel, Christel Moog-lutz, Yvon E. CayreAbstract:A pivotal role has been assigned to Myb in the control of myeloid cell growth. Although Myb is a target of retinoic acid, little is known about the mechanisms by which it may contribute to induced growth arrest in leukemia cells. Indeed, few Myb target genes are known to be linked to proliferation. Myeloblastin is involved in the control of proliferation in myeloid leukemia cells. It is expressed early during hematopoiesis and is a granulocyte colony-stimulating factor–responsive gene. Myeloblastin can confer factor-independent growth to hematopoietic cells, an early step in leukemia transformation. The Myeloblastin promoter contains PU.1, C/EBP, and Myb binding sites, each of which are critical for constitutive expression in myeloid cells. Inhibition of Myeloblastin expression in leukemia cells growth-arrested by retinoic acid is demonstrated to depend on Myb down-regulation. Myb is shown to induce Myeloblastin expression and abolish its down-regulation by retinoic acid. Altogether, the data offer a clue as to how a myeloid-specific transcriptional machinery can be accessible to regulation by retinoic acid and point to Myeloblastin as a novel target of Myb. This link between Myb and Myeloblastin suggests a previously nonidentified Myb pathway through which growth arrest is induced by retinoic acid in myeloid leukemia cells.
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Myeloblastin is a granulocyte colony-stimulating factor-responsive gene conferring factor-independent growth to hematopoietic cells.
Proceedings of the National Academy of Sciences of the United States of America, 2000Co-Authors: Pierre G. Lutz, Christel Moog-lutz, Edith Coumau-gatbois, Ladan Kobari, Yolande Di Gioia, Yvon E. CayreAbstract:Hematopoiesis depends on a pool of quiescent hematopoietic stem/progenitor cells. When exposed to specific cytokines, a portion of these cells enters the cell cycle to generate an amplified progeny. Myeloblastin (MBN) initially was described as involved in proliferation of human leukemia cells. The granulocyte colony-stimulating factor (G-CSF), which stimulates the proliferation of granulocytic precursors, up-regulates MBN expression. Here we show that constitutive overexpression of MBN confers factor-independent growth to murine bone marrow-derived Ba/F3/G-CSFR cells. Our results point to MBN as a G-CSF responsive gene critical to factor-independent growth and indicate that expression of the G-CSF receptor is a prerequisite to this process. A 91-bp MBN promoter region containing PU.1, C/EBP, and c-Myb binding sites is responsive to G-CSF treatment. Although PU.1, C/EBP, and c-Myb transcription factors all were critical for expression of MBN, its up-regulation by G-CSF was associated mainly with PU.1. These findings suggest that MBN is an important target of PU.1 and a key protease for factor-independent growth of hematopoietic cells.
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Genomic organization and chromosomal localization of mouse proteinase 3 (Myeloblastin).
Mammalian genome : official journal of the International Mammalian Genome Society, 1999Co-Authors: A. Belaaouaj, Christel Moog-lutz, Jocelyne Just, A. Houzel-charavel, Steven D. Shapiro, Yvon E. CayreAbstract:Proteinase 3 (PR3), is a matrix-degrading serine proteinase expressed in different hematopoietic cell lineages. The PR3 protein appears to regulate the myeloid differentiation and was found to be the autoantigen associated with Wegener granulomatosis. We have isolated and characterized the gene for mouse PR3 (mPR3) and determined its chromosomal location. The gene has been localized to Chromosome (Chr) 10. Comparison of mouse PR3 genomic structure with that of its human counterpart indicates that: 1) the mPR3 gene spans 7 kb organized in 5 exons and 4 introns, 2) the codons of His-Asp-Ser of the catalytic site are conserved and spread out over different exons, similar to the human gene, and 3) the gene product encodes a pre-proform of the protein. Knowledge of the structure and chromosomal location of the mPR3 gene may help better the understanding of the temporal and cell-specific expression of mouse PR3.
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Regulation of Myeloblastin messenger RNA expression in myeloid leukemia cells treated with all-trans retinoic acid
Blood, 1993Co-Authors: C Labbaye, Jin Zhang, Jean-laurent Casanova, Michel Lanotte, Jianye Teng, Wilson H. Miller, Yvon E. CayreAbstract:Retinoic acid is known to induce differentiation of human myeloid leukemia cells in vitro. Recently, all-trans retinoic acid has been used to induce remissions in patients with acute promyelocytic leukemia, probably through differentiation of the leukemia cells. Myeloblastin (mbn) is a protease that has been identified in the human leukemia cell line HL-60. Downregulation of this protease can inhibit proliferation and induce differentiation of HL-60-derived leukemia cells. Here we have investigated the regulation of mbn messenger RNA (mRNA) expression in two human leukemia cell lines, HL-60 and NB4, treated with all-trans retinoic acid. Under this treatment, downregulation of mbn mRNA was observed in both cell lines, but was considerably delayed in NB4 cells that carry the t(15;17) translocation characteristic of acute promyelocytic leukemia. We have found that multiple mechanisms were involved in the control of mbn mRNA expression. These mechanisms were different in HL-60 and NB4 cells. Our results show that in HL-60 cells, all-trans retinoic acid rapidly decreased transcription of mbn. In contrast, in the t(15;17)-positive NB4 cells treated with all-trans retinoic acid, upregulation of mbn mRNA expression was followed by a late downregulation, both achieved via posttranscriptional mechanisms.
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Wegener autoantigen and Myeloblastin are encoded by a single mRNA.
Proceedings of the National Academy of Sciences of the United States of America, 1991Co-Authors: C Labbaye, P Musette, Yvon E. CayreAbstract:Abstract Myeloblastin is a serine protease that has been identified in the human leukemia cell line HL-60. Down-regulation of this protease can inhibit proliferation and induce differentiation of promyelocyte-like human leukemic cells. Proteinase 3, a serine protease of human neutrophils, has been identified as the Wegener autoantigen. A high level of homology between Myeloblastin and proteinase 3 has suggested that they may be a single serine protease. We have recently completed the 5'-terminal nucleotide sequence of proteinase 3 and shown that its mRNA was also expressed in HL-60 cells and in cells from patients with acute myeloid leukemia. Here we demonstrate that Myeloblastin and proteinase 3 are encoded by a single mRNA.
J. Schwaller - One of the best experts on this subject based on the ideXlab platform.
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a Myeloblastin proteinase 3 cdna clone identifies a bglii and a pvuii restriction fragment length polymorphism
Human Genetics, 1993Co-Authors: J. Schwaller, T. Chen, M. F. Fey, A. ToblerAbstract:A Myeloblastin/proteinase-3 (MBN/PR-3) cDNA probe detects two bi-allelic (BglII, PvuII) DNA polymorphisms. These restriction fragment length polymorphisms provide new genetic markers on chromosome 19.
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A Myeloblastin/proteinase-3 cDNA clone identifies a BglII and a PvuII restriction fragment length polymorphism.
Human Genetics, 1993Co-Authors: J. Schwaller, T. Chen, M. F. Fey, A. ToblerAbstract:A Myeloblastin/proteinase-3 (MBN/PR-3) cDNA probe detects two bi-allelic (BglII, PvuII) DNA polymorphisms. These restriction fragment length polymorphisms provide new genetic markers on chromosome 19.
T. Chen - One of the best experts on this subject based on the ideXlab platform.
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a Myeloblastin proteinase 3 cdna clone identifies a bglii and a pvuii restriction fragment length polymorphism
Human Genetics, 1993Co-Authors: J. Schwaller, T. Chen, M. F. Fey, A. ToblerAbstract:A Myeloblastin/proteinase-3 (MBN/PR-3) cDNA probe detects two bi-allelic (BglII, PvuII) DNA polymorphisms. These restriction fragment length polymorphisms provide new genetic markers on chromosome 19.
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A Myeloblastin/proteinase-3 cDNA clone identifies a BglII and a PvuII restriction fragment length polymorphism.
Human Genetics, 1993Co-Authors: J. Schwaller, T. Chen, M. F. Fey, A. ToblerAbstract:A Myeloblastin/proteinase-3 (MBN/PR-3) cDNA probe detects two bi-allelic (BglII, PvuII) DNA polymorphisms. These restriction fragment length polymorphisms provide new genetic markers on chromosome 19.
M. F. Fey - One of the best experts on this subject based on the ideXlab platform.
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a Myeloblastin proteinase 3 cdna clone identifies a bglii and a pvuii restriction fragment length polymorphism
Human Genetics, 1993Co-Authors: J. Schwaller, T. Chen, M. F. Fey, A. ToblerAbstract:A Myeloblastin/proteinase-3 (MBN/PR-3) cDNA probe detects two bi-allelic (BglII, PvuII) DNA polymorphisms. These restriction fragment length polymorphisms provide new genetic markers on chromosome 19.
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A Myeloblastin/proteinase-3 cDNA clone identifies a BglII and a PvuII restriction fragment length polymorphism.
Human Genetics, 1993Co-Authors: J. Schwaller, T. Chen, M. F. Fey, A. ToblerAbstract:A Myeloblastin/proteinase-3 (MBN/PR-3) cDNA probe detects two bi-allelic (BglII, PvuII) DNA polymorphisms. These restriction fragment length polymorphisms provide new genetic markers on chromosome 19.
