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 have isolated non-globin cDNA clones specific for erythroid differentiation from K562 human erythroleukemia cells and have identified those that may regulate globin gene transcription. A cDNA library was constructed from K562 cells induced by hemin for production of embryonic and fetal hemoglobins and screened against cDNA from uninduced K562 cells. Full-length clones specific for induced K562 cells were ligated into a eukaryotic expression vector and transfected into HeLa cells to allow for production of the corresponding coded polypeptide. The ability to increase epsilon- or gamma-globin promoter activity was identified using cotransfection with a second vector containing a globin gene promoter fused to a reporter gene. Six of the induced K562-specific clones exhibited the ability to increase the levels of the reporter genes, bacterial chloramphenicol acetyltransferase and human growth hormone. Sequencing analyses of these clones indicated that five were homologous to ferritin heavy and light chains and one had no homology with known DNA or protein sequences. The ferritin light chain cDNA had the greatest effect on globin gene promoter activation, increasing the gamma-globin promoter activity by 6-8-fold. The activation of the globin gene promoter in the absence of globin gene translation suggests that ferritin (or iron) may have a direct role in globin gene transcription. The subtractive library cloning strategy has enabled us to isolate cDNA clones that activate specific gene promoter without the requirement of direct DNA binding. This approach may allow further identification of the genes encoding proteins that are involved in the control of erythropoiesis.
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PMID:Activation of globin gene expression by cDNAs from induced K562 cells. Evidence for involvement of ferritin in globin gene expression. 184 May 94

Cellular iron metabolism is altered during chronic inflammatory states, leading to reticuloendothelial iron sequestration and an associated anemia. To study the effects of nitric oxide (NO) on the expression of three genes involved in erythroid cell iron metabolism (gamma-globin, H-ferritin, and transferrin receptor [TfR]), we developed a series of human K562 erythroleukemic cell clones retrovirally transduced with inducible nitric oxide synthase (NOS-2) and producing different steady-state levels of NO. gamma-Globin and H-ferritin protein expression was reduced in NO-producing cells in relation to the amount of NO produced. Conversely, cell surface TfR expression increased in NO-producing clones. Both the inhibitory effects of NO on gamma-globin and H-ferritin expression and the stimulatory effect on TfR were reversed by the NOS inhibitor NG-methyl-L-arginine (NGMMA). gamma-Globin and H-ferritin mRNA levels were unaffected by NO production. In the case of TfR, NO appeared to stabilize mRNA in that the half life of TfR mRNA decreased from approximately 15 hours to less than 3 hours when NO production by NOS-transduced clones was inhibited. Thus, NO can regulate expression of these genes at the posttranscriptional level, an effect that is likely mediated by the known effect of NO on the RNA binding activity of iron regulatory protein-1 (Pantopoulos and Hentze, Proc Natl Acad Sci USA 92:1267, 1995). Furthermore, our findings suggest a mechanism for the observed relationship between NO production and the pathophysiology of the anemia of chronic disease.
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PMID:Nitric oxide alters the expression of gamma-globin, H-ferritin, and transferrin receptor in human K562 cells at the posttranscriptional level. 887 95

The Ninth Cooley's Symposium provided an outstanding summary of progress in the field. Highlights of the conference included the report of clinical benefit in one of two patients treated in a gene therapy trial. Another major breakthrough was the report that the transcriptional factor, BCL11A, is a key molecular component of the gamma-globin silencing mechanism that results in the fetal to adult perinatal switch. The ability to evaluate tissue iron is becoming increasingly more sophisticated, with results presented at this conference indicating that independent measurement of cardiac ferritin and hemosiderin can be achieved with specific MRI sequences. The three available iron chelators, deferoxamine, deferiprone, and deferasirox, provide a potent therapeutic armamentarium so that effective chelation regimens can be devised for most individual patients. Unfortunately, compliance remains a significant issue despite the availability of oral chelators. Modification of conditioning regimens and the use of alternative donor sources have made stem cell transplantation available to an increasing number of patients with progressive improvement in outcome. Despite many advances, the global burden of disease for the thalassemias remains very high, with many challenges that still need to be addressed in order to optimize treatment for the majority of patients.
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PMID:Ninth Cooley's Anemia Symposium: summary and perspective. 2071 1