BIOMAT Database Logo BIOMAT Database Logo

Loss of erythropoietin responsiveness in erythroid progenitors due to expression of the Evi-1 myeloid-transforming gene. 1993

B L Kreider, and S H Orkin, and J N Ihle
Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN 38105.

Inappropriate expression of the Evi-1 zinc-finger gene in hematopoietic cells has been associated with acute myelogenous leukemia and myelodysplastic syndromes in murine models and in humans. Consistent with this, previous studies have shown that aberrant expression of the Evi-1 gene in a myeloid progenitor cell line blocks granulocytic differentiation. Here we demonstrate that the aberrant expression of the Evi-1 gene impairs the normal response of erythroid cells or bone-marrow progenitors to erythropoietin. Erythroid differentiation has been shown to require the GATA-1 transcription factor that binds to a sequence contained within the consensus binding sequence identified for Evi-1. In the studies presented here we also show that Evi-1 can repress GATA-1-dependent transactivation in transient chloramphenicol acetyltransferase assays. Together the data support the hypothesis that inappropriate expression of the Evi-1 gene blocks erythropoiesis by repressing the transcription of a subset of GATA-1 target genes.

UI MeSH Term Description Entries
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D011401 Promoter Regions, Genetic DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes. rRNA Promoter,Early Promoters, Genetic,Late Promoters, Genetic,Middle Promoters, Genetic,Promoter Regions,Promoter, Genetic,Promotor Regions,Promotor, Genetic,Pseudopromoter, Genetic,Early Promoter, Genetic,Genetic Late Promoter,Genetic Middle Promoters,Genetic Promoter,Genetic Promoter Region,Genetic Promoter Regions,Genetic Promoters,Genetic Promotor,Genetic Promotors,Genetic Pseudopromoter,Genetic Pseudopromoters,Late Promoter, Genetic,Middle Promoter, Genetic,Promoter Region,Promoter Region, Genetic,Promoter, Genetic Early,Promoter, rRNA,Promoters, Genetic,Promoters, Genetic Middle,Promoters, rRNA,Promotor Region,Promotors, Genetic,Pseudopromoters, Genetic,Region, Genetic Promoter,Region, Promoter,Region, Promotor,Regions, Genetic Promoter,Regions, Promoter,Regions, Promotor,rRNA Promoters
D011519 Proto-Oncogenes Normal cellular genes homologous to viral oncogenes. The products of proto-oncogenes are important regulators of biological processes and appear to be involved in the events that serve to maintain the ordered procession through the cell cycle. Proto-oncogenes have names of the form c-onc. Proto-Oncogene,Proto Oncogene,Proto Oncogenes
D001853 Bone Marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Marrow,Red Marrow,Yellow Marrow,Marrow, Bone,Marrow, Red,Marrow, Yellow
D002455 Cell Division The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION. M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D004268 DNA-Binding Proteins Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases. DNA Helix Destabilizing Proteins,DNA-Binding Protein,Single-Stranded DNA Binding Proteins,DNA Binding Protein,DNA Single-Stranded Binding Protein,SS DNA BP,Single-Stranded DNA-Binding Protein,Binding Protein, DNA,DNA Binding Proteins,DNA Single Stranded Binding Protein,DNA-Binding Protein, Single-Stranded,Protein, DNA-Binding,Single Stranded DNA Binding Protein,Single Stranded DNA Binding Proteins
D004921 Erythropoietin Glycoprotein hormone, secreted chiefly by the KIDNEY in the adult and the LIVER in the FETUS, that acts on erythroid stem cells of the BONE MARROW to stimulate proliferation and differentiation.
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D005822 Genetic Vectors DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition. Cloning Vectors,Shuttle Vectors,Vectors, Genetic,Cloning Vector,Genetic Vector,Shuttle Vector,Vector, Cloning,Vector, Genetic,Vector, Shuttle,Vectors, Cloning,Vectors, Shuttle
D000074008 MDS1 and EVI1 Complex Locus Protein A DNA binding protein, transcriptional regulator, and proto-oncogene protein that contains 10 CYS2-HIS2 ZINC FINGERS. It functions as a positive or negative regulator of expression for target genes involved in organism development. Ecotropic Virus Integration Site 1 Protein Homolog,MECOM Protein,Myelodysplasia Syndrome-Associated Protein 1,Zinc Finger Protein Evi1,Myelodysplasia Syndrome Associated Protein 1

Related Publications

B L Kreider, and S H Orkin, and J N Ihle
[Erythropoietin responsiveness of erythroid progenitor cells--with special reference to the altered erythropoietin responsiveness of erythroid progenitors in polycythemia vera].
May 1985, [Rinsho ketsueki] The Japanese journal of clinical hematology,
B L Kreider, and S H Orkin, and J N Ihle
Erythroid responsiveness to erythropoietin in hypophysectomized rats.
January 1966, Acta physiologica latino americana,
B L Kreider, and S H Orkin, and J N Ihle
Responsiveness to recombinant human erythropoietin of marrow erythroid progenitors from infants with the "anemia of prematurity".
June 1988, The Journal of pediatrics,
B L Kreider, and S H Orkin, and J N Ihle
Retroviral insertions 90 kilobases proximal to the Evi-1 myeloid transforming gene activate transcription from the normal promoter.
April 1991, Molecular and cellular biology,
B L Kreider, and S H Orkin, and J N Ihle
The Evi-1 zinc finger myeloid transforming gene is normally expressed in the kidney and in developing oocytes.
September 1990, Oncogene,
B L Kreider, and S H Orkin, and J N Ihle
EVI-1 gene expression in myeloid clonogenic cells from juvenile myelomonocytic leukemia (JMML).
December 1997, Leukemia,
B L Kreider, and S H Orkin, and J N Ihle
Erythropoietin & erythroid progenitors in rats exposed to chronic hypoxia.
November 1996, The Indian journal of medical research,
B L Kreider, and S H Orkin, and J N Ihle
Expression of Sara2 human gene in erythroid progenitors.
May 2005, Journal of biochemistry and molecular biology,
B L Kreider, and S H Orkin, and J N Ihle
Primary familial polycythemia: a frameshift mutation in the erythropoietin receptor gene and increased sensitivity of erythroid progenitors to erythropoietin.
July 1995, Blood,
B L Kreider, and S H Orkin, and J N Ihle
Expression of the Evi-1 gene in myelodysplastic syndromes.
January 1995, Leukemia,
Copied contents to your clipboard!