Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.1.17 (ornithine decarboxylase)
 6,351 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

alpha-Difluoromethylornithine (DFMO) and methyl acetylene putrescine (MAP) are inhibitors of the rate limiting enzyme in polyamine synthesis, ornithine decarboxylase. We studied the effects of these compounds on the formation of retrovirus transformed erythroid colonies. DFMO was able to effectively reduce the number of transformed colonies at a concentration of 10(-3) M, whereas MAP achieved total inhibition at 10(-4) M. Putrescine, the product of ornithine decarboxylase, did not alter colony number by itself but it was able to overcome the inhibitory effects of both DFMO and MAP. Addition of DFMO at times after the initiation of culture decreased its effectiveness in reducing transformed colony numbers, while the converse was true for the erythroid stimulant, erythropoietin. We concluded from these data that DFMO and MAP probably diminished colony formation by inhibiting proliferation of the target cells for the retroviruses.
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PMID:Effect of inhibitors of ornithine decarboxylase on retrovirus induced transformation of murine erythroid precursors in vitro. 309 57

The ability to adapt successfully to periods of relative hypoxia is crucial to the survival of all higher life forms. Several genes have previously been identified which are up-regulated in response to hypoxia; these include the genes encoding erythropoietin (Epo), platelet-derived growth factor B chain, endothelin, interleukin-1 alpha, ornithine decarboxylase, and vascular endothelial growth factor (VEGF). However, the molecular mechanisms by which hypoxia is sensed remain enigmatic. In addition, it is unknown whether the genes mentioned share a common oxygen-sensing signal transduction pathway. In this report we demonstrate multiple similarities between the oxygen-sensing mechanisms regulating the expression of VEGF and Epo. The expression of both mRNAs is significantly up-regulated by hypoxia and cobalt chloride (CoCl2), and the half-life of both mRNAs is markedly prolonged by cycloheximide. In addition, hypoxic induction of both Epo and VEGF is inhibited by carbon monoxide. As part of our investigation into the signal transduction pathway responsible for the hypoxia and cobalt induction of these genes, we discovered that the expression of members of the jun and fos protooncogene families is also up-regulated early after exposure to either of these stimuli. These findings provide support for the hypothesis that the mechanism(s) by which hypoxia is sensed at a molecular level may be highly conserved and tightly regulated.
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PMID:Similarities between the oxygen-sensing mechanisms regulating the expression of vascular endothelial growth factor and erythropoietin. 830 5

The cytoplasmic domain of the erythropoietin receptor (EpoR) contains a region, proximal to the transmembrane domain, that is essential for function and has homology with other members of the cytokine receptor family. To explore the functional significance of this region and to identify critical residues, we introduced several amino acid substitutions and examined their effects on erythropoietin-induced mitogenesis, tyrosine phosphorylation, and expression of immediate-early (c-fos, c-myc, and egr-1) and early (ornithine decarboxylase and T-cell receptor gamma) genes in interleukin-3-dependent cell lines. Amino acid substitution of W-282, which is strictly conserved at the middle portion of the homology region, completely abolished all the functions of the EpoR. Point mutation at L-306 or E-307, both of which are in a conserved LEVL motif, drastically impaired the function of the receptor in all assays. Other point mutations, introduced into less conserved amino acid residues, did not significantly impair the function of the receptor. These results demonstrate that conserved amino acid residues in this domain of the EpoR are required for mitogenesis, stimulation of tyrosine phosphorylation, and induction of immediate-early and early genes.
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PMID:Inactivation of erythropoietin receptor function by point mutations in a region having homology with other cytokine receptors. 838 75