Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the possibility that insulin could stimulate translation of ornithine decarboxylase (ODC) mRNA in a murine fibroblast cell line that expresses large numbers of human insulin receptors (HIR 3.5 cells). Within 3 h after exposure to 70 nM insulin, ODC enzyme activity increased approximately 50-fold and mRNA accumulation 3-fold in the HIR 3.5 cells but not in normal fibroblasts. Pretreatment of cells with cycloheximide completely inhibited insulin-stimulated ODC expression; actinomycin D partially inhibited this effect. To determine the influence of the 5' untranslated region (5'UTR) of ODC mRNA on insulin-regulated ODC expression, plasmids were constructed which contained sequences from the 5'UTR of a rat ODC mRNA interposed between the ferritin promoter and the coding region of the human growth hormone gene. These constructions were then expressed transiently in HIR 3.5 cells. Insulin stimulated a 2-4-fold change in growth hormone accumulation in the medium of cells transiently expressing plasmids containing the entire 5'UTR of ODC mRNA or just the 5'-most 115 bases, a G/C-rich conserved sequence predicted to form a stem-loop structure and shown previously to be responsible for constitutive inhibition of translation. There was a direct correlation between the extent of insulin stimulation and the predicted secondary structure of the added 5'UTR sequences. To determine whether this effect might be due to insulin activation of initiation factors responsible for melting mRNA secondary structure, we examined the effect of insulin on the phosphorylation states of two such factors, eucaryotic initiation factors eIF-4B and eIF-4E. Insulin stimulated the phosphorylation of both initiation factors; this stimulation was evident at 15 min and maximal by 60 min. These results suggest a potential general mechanism by which insulin could preferentially stimulate translation of mRNAs whose 5'UTRs exhibit significant secondary structure by activating initiation factors involved in melting such secondary structures.
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PMID:Insulin induction of ornithine decarboxylase. Importance of mRNA secondary structure and phosphorylation of eucaryotic initiation factors eIF-4B and eIF-4E. 198 89

Hydroxyurea was used to select two very highly drug resistant cell lines, designated HR-15 and HR-30. Both drug resistant lines contained elevated levels of ribonucleotide reductase activity. Northern and Southern blot analysis indicated that the two drug resistant lines contained increased levels of mRNA for the two components, M1 and M2, of ribonucleotide reductase, and M1 and M2 gene amplifications. Alterations in M1 and M2 protein levels were also evident in Western blot analysis. Further studies of HR-15 and HR-30 cells by Northern and Southern blot analysis showed that the drug resistant cell lines had elevated levels of ornithine decarboxylase mRNA and p5-8 mRNA, as well as increased ornithine decarboxylase and p5-8 gene copy numbers, respectively. Furthermore, characterization of HR-15 and HR-30 drug-resistant cell lines revealed increased mRNA levels for both H- and L-ferritin. Both cell lines exhibited by Southern blot analysis, amplification of the H- and L-ferritin genes. Increases in the cellular levels of H- and L-ferritin subunit proteins were also observed in both HR-15 and HR-30 cells, by Western blot analysis. This is the first description of mutant cell lines containing this complex combination of modified gene expressions and gene amplifications. The alterations exhibited by these lines confirm and extend present models of hydroxyurea resistance, are in agreement with and help substantiate models of ribonucleotide reductase regulation and provide interesting links between the expressions of several cellular activities important in proliferation.
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PMID:Mammalian drug resistant mutants with multiple gene amplifications: genes encoding the M1 component of ribonucleotide reductase, the M2 component of ribonucleotide reductase, ornithine decarboxylase, p5-8, the H-subunit of ferritin and the L-subunit of ferritin. 222 78

Over-expression of the transcription factor c-Myc immortalizes primary cells and transforms in co-operation with activated ras. Therefore, c-myc is considered a proto-oncogene. Since its discovery c-Myc has been shown to render cells growth factor independent, accelerates passage through G1 of the cell cycle, inhibits differentiation and elicits apoptosis. Whereas the effects on immortalization, proliferation and inhibition of differentiation are in conceivable accordance with gain of function, as it is defined for a proto-oncogene, its pro-apoptotic activity disables a straight forward explanation of the physiological role of c-Myc and suggests a highly complex contribution during development. The recent accomplishments in c-Myc research shed some light on the difficile regulatory network which keeps check on c-Myc activity such as by binding to proteins some of which are transcription factors for non-c-Myc targets. Moreover, it was shown that genes are targeted by c-Myc depending on the sequence of flanking regions adjacent to the E-box or in dependence on the availability of binding partners which is most probably specific to the cellular context. Cdc25A and ornithine decarboxylase, both described to be c-Myc targets, have been brought forward as downstream effectors in the induction of proliferation under serum rich conditions, or in the induction of apoptosis when serum factors are limited. These genes seem to be regulated by c-Myc in a cell type-specific manner. H-ferritin, IRP2 and telomerase are the most recently discovered direct targets of c-Myc. The regulation of H-ferritin and IRP2 might explain the potential of c-Myc to promote proliferation and the regulation of telomerase could be responsible for the immortalizing properties of c-Myc. In the future, H-ferritin and telomerase have to be analyzed whether or not these genes are also Myc targets in other cell systems. Although the intense research efforts regarding the function of c-Myc last already two decades the role of this gene is still enigmatic.
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PMID:The MYC dualism in growth and death. 1059 28